|
1
|
Seth G, Singh S, Sharma G, Suvedi D, Kumar D, Nagraik R, Sharma A. Harnessing the power of stem cell-derived exosomes: a rejuvenating therapeutic for skin and regenerative medicine. 3 Biotech 2025; 15:184. [PMID: 40417660 PMCID: PMC12102458 DOI: 10.1007/s13205-025-04345-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 05/04/2025] [Indexed: 05/27/2025] Open
Abstract
Exosomes are small extracellular vesicles produced by most cell types and contain proteins, lipids, and nucleic acids (non-coding RNAs, mRNA, and DNA) that can be released by donor cells to influence the function of recipient cells. Skin photoaging is the premature aging of skin structures caused by prolonged exposure to ultraviolet (UV), as demonstrated by depigmentation, roughness, rhytides, elastosis, and precancerous alterations. Exosomes are associated with aging processes such as oxidative damage, inflammation, and senescence. Exosomes' anti-aging properties have been linked to various in vitro and preclinical investigations. There are still several unanswered questions about the use of MSC exosomes for skin rejuvenation, despite encouraging results. Uncertainty surrounds the precise processes by which exosomes stimulate the creation of collagen, skin tissue via a variety of mechanisms, including reduced matrix metalloproteinase (MMP) expression, increased collagen and elastin production, and modulation of intracellular signaling pathways and intercellular communication. These findings suggest the therapeutic potential of exosomes in skin aging. This review provides information on the molecular mechanisms and consequences of exosome anti-aging.
Collapse
Affiliation(s)
- Gracy Seth
- Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh 173229 India
| | - Siddharth Singh
- Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh 173229 India
| | - Geetansh Sharma
- Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh 173229 India
| | - Divyesh Suvedi
- Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh 173229 India
| | - Dinesh Kumar
- Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh 173229 India
| | - Rupak Nagraik
- Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh 173229 India
- Department of Biotechnology, Graphic Era (Deemed to Be University), Dehradun, 248002 India
| | - Avinash Sharma
- Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh 173229 India
- Department of Biotechnology, Graphic Era (Deemed to Be University), Dehradun, 248002 India
| |
Collapse
|
|
2
|
Renu K. Exosomes derived from human adipose mesenchymal stem cells act as a therapeutic target for oral submucous fibrosis. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2025; 126:102224. [PMID: 39765310 DOI: 10.1016/j.jormas.2025.102224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 01/03/2025] [Indexed: 01/11/2025]
Abstract
Oral submucosal fibrosis is a highly malignant oral condition that necessitates the use of sophisticated therapeutic procedures. OSF is a multifactorial precancerous condition induced by areca nut chewing, deficiencies in vitamins and trace minerals, immunological aspects, and hereditary factors. Adipose tissue-derived mesenchymal stem cells possess the capability for multidirectional activation and are extensively distributed throughout the body. They have minimal immunogenicity and are extensively utilized in cancer treatment. Exosomes are extracellular vesicles produced by the intracellular route. They are biological carriers comprising microRNA, messenger RNA, lipids and proteins crucial for intercellular communication. ADSC exosomes, serving as a vehicle for miRNA, possess accessibility and little immunogenicity. They can significantly contribute to adipose tissue regrowth, angiogenesis, immunological modulation, and tissue repair. ADSC-Exo exhibits antifibrotic properties and may serve as a potential treatment for OSF. This review presents a novel therapeutic approach and clarifies the precise mechanisms involved in the clinical management of OSF using ADSC-Exo.
Collapse
Affiliation(s)
- Kaviyarasi Renu
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 600077, Tamil Nadu, India.
| |
Collapse
|
|
3
|
Chen Y, Yin W, Liu Z, Lu G, Zhang X, Yang J, Huang Y, Hu X, Chen C, Shang R, Hu W, Wang J, Shen HM, Hu J, Luo G, He W. Exosomes derived from fibroblasts enhance skin wound angiogenesis by regulating HIF-1α/VEGF/VEGFR pathway. BURNS & TRAUMA 2025; 13:tkae071. [PMID: 40433567 PMCID: PMC12107542 DOI: 10.1093/burnst/tkae071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 10/19/2024] [Accepted: 10/30/2024] [Indexed: 05/29/2025]
Abstract
Background Angiogenesis is vital for tissue repair but insufficient in chronic wounds due to paradoxical growth factor overexpression yet reduced neovascularization. Therapeutics physiologically promoting revascularization remain lacking. This study aims to investigate the molecular mechanisms underlying fibroblast-derived exosome-mediated angiogenesis during wound repair. Methods To assess the effects of fibroblasts derived exosomes on wound healing and angiogenesis, a full-thickness mouse skin injury model was established, followed by pharmacological inhibition of exosome secretion. The number and state of blood vessels in wounds were assessed by immunofluorescence, immunohistochemistry, hematoxylin-eosin staining, and laser Doppler imaging system. The high-throughput miRNA sequencing was carried out to detect the miRNA profiles of fibroblast-derived exosomes. The roles of candidate miRNAs, their target genes, and relevant pathways were predicted by bioinformatic online software. The knockdown and overexpression of candidate miRNAs, co-culture system, matrigel assay, pharmacological blockade, cell migration, EdU incorporation assay, and cell apoptosis were employed to investigate their contribution to angiogenesis mediated by fibroblast-derived exosomes. The expression of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia-inducible factor 1α (HIF-1α), von Hippel-Lindau (VHL), and proline hydroxylases 2 was detected by western blot, co-immunoprecipitation, immunofluorescence, real-time quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. Furthermore, a full-thickness mouse skin injury model based on type I diabetes mellitus induced by streptozotocin was established for estimating the effect of fibroblast-derived exosomes on chronic wound healing. Results Pharmacological inhibition of exosome biogenesis markedly reduces neovascularization and delays murine cutaneous wound closure. Topical administration of fibroblast-secreted exosomes rescues these defects. Mechanistically, exosomal microRNA-24-3p suppresses VHL E3 ubiquitin ligase levels in endothelial cells to stabilize hypoxia-inducible factor-1α and heighten vascular endothelial growth factor signaling. MicroRNA-24-3p-deficient exosomes exhibit attenuated pro-angiogenic effects. Strikingly, topical application of exosomes derived from fibroblasts onto chronic wounds in diabetic mice improves neovascularization and healing dynamics. Conclusions Overall, we demonstrate central roles for exosomal miR-24-3p in stimulating endothelial HIF-VEGF signaling by inhibiting VHL-mediated degradation. The findings establish fibroblast-derived exosomes as promising acellular therapeutic candidates to treat vascular insufficiency underlying recalcitrant wounds.
Collapse
Affiliation(s)
- Yunxia Chen
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
- Chongqing Key Lab for Wound Repair and Tissue Regeneration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Wenjing Yin
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
- Chongqing Key Lab for Wound Repair and Tissue Regeneration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Zhihui Liu
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
- Chongqing Key Lab for Wound Repair and Tissue Regeneration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Guang Lu
- Zhongshan School of Medicine, Sun Yat-sen University, Zhongshan second road, Yuexiu district, Guangzhou 510062, China
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 21 Lower Kent Ridge Road, Singapore 119077, Singapore
| | - Xiaorong Zhang
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
- Chongqing Key Lab for Wound Repair and Tissue Regeneration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Jiacai Yang
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
- Chongqing Key Lab for Wound Repair and Tissue Regeneration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Yong Huang
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
- Chongqing Key Lab for Wound Repair and Tissue Regeneration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Xiaohong Hu
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
- Chongqing Key Lab for Wound Repair and Tissue Regeneration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Cheng Chen
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Ruoyu Shang
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Wengang Hu
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Jue Wang
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Han-Ming Shen
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 21 Lower Kent Ridge Road, Singapore 119077, Singapore
- Faculty of Health Sciences, Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Macao Taipa University Avenue, Macau 999078, China
| | - Jun Hu
- Department of Neurology, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Gaoxing Luo
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
- Chongqing Key Lab for Wound Repair and Tissue Regeneration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| | - Weifeng He
- State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
- Chongqing Key Lab for Wound Repair and Tissue Regeneration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Gaotanyan street, Shapingba district, Chongqing 400038, China
| |
Collapse
|
|
4
|
Cui L, Song Y, Hou Z, Yang L, Guo S, Wang C. From bench to bedside: the research status and application opportunity of extracellular vesicles and their engineering strategies in the treatment of skin defects. J Nanobiotechnology 2025; 23:375. [PMID: 40414838 DOI: 10.1186/s12951-025-03461-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 05/11/2025] [Indexed: 05/27/2025] Open
Abstract
Engineered extracellular vesicles (EVs), which are EVs modified to enhance certain biological properties, offer a promising therapeutic strategy for the treatment of skin defects. Conventional nanomaterials often encounter clinical translation challenges due to potential toxicity and limited targeting. Engineered EVs, utilizing inherent biocompatibility and effective physiological barrier traversal, can ameliorate the limitations of conventional EV therapies to some extent, including detection, isolation, purification, and therapeutic validation. Recent advances in EV engineering, such as genetic modification of production cells to control cargo, surface engineering for targeted delivery, and pre-treatment of parental cells to optimize production and bioactivity, have improved therapeutic efficacy in laboratory studies through enhanced targeting, prolonged retention time, and increased yield. Many studies have suggested the potential ability of engineered EVs to treat a variety of skin defects, including diabetic wounds, burns, and hypertrophic scars, providing a promising avenue for their clinical translation in this area. This paper reviews the therapeutic potential of engineered EVs in skin regeneration, highlighting their role in promoting cell migration and angiogenesis, modulating inflammation and reducing scar formation during wound healing. In addition, given the investment in this rapidly evolving field and the growing clinical trial activity, this review also explores recent global advances and provides an outlook on future application opportunities for EVs in the treatment of skin defects.
Collapse
Affiliation(s)
- Longwei Cui
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, 110002, People's Republic of China
| | - Yantao Song
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, 110002, People's Republic of China
| | - Zhipeng Hou
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People's Republic of China
| | - Liqun Yang
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People's Republic of China.
| | - Shu Guo
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, 110002, People's Republic of China.
| | - Chenchao Wang
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, 110002, People's Republic of China.
| |
Collapse
|
|
5
|
Du J, Wu J, Song Q, Li S, Hong Y, Anwar A, Fu Q, Liu J. Mesenchymal stem cell exosomes regulate TGFβ/Smad3 by decreasing the METTL3-NEAT1 axis to inhibit scar progression after breast surgery. J Mol Histol 2025; 56:161. [PMID: 40392368 DOI: 10.1007/s10735-025-10441-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Accepted: 04/25/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Scars are traces of tissue loss left behind by connective tissue overgrowth and repair. Studies in recent years have shown that mesenchymal stem cell exosomes (MSC-Exo) have the ability to inhibit and repair cutaneous scarring, but their specific role in post-breast surgery scar formation and the mechanisms behind it remain enigmatic. METHODS Extraction and characterization of exosomes from mesenchymal stem cells (MSCs). Western Blot and RT-qPCR were used to evaluate the expression of fibrillar protein and TGF-β/Smad3 in mammary hypertrophic scar fibroblasts (MHSFs) stimulated with MSC-Exo, sh-METTL3, sh-NEAT1 and their negative controls. Construction of a mouse model of proliferative scar formation using mechanical tension and detection of fibronectin and pathway protein expression using Western Blot and RT-qPCR. Pathologic changes of mammary scarring in mice using HE staining, Masson staining and immunofluorescence. RESULTS Both in vitro and in vivo, MSC-Exo, sh-METTL3 and sh-NEAT1 were shown to decrease the expression of COL1A1, COL3A1, α-SMA, fibronectin, TGF-β, p-Smad2/Smad2, p-Smad3/Smad3, by Western Blot and RT-qPCR. In addition, improved lesions and reduced collagen deposition were observed in mice by HE and Masson assays. CONCLUSIONS In summary, our study revealed that exosomes of MSCs function through the m6A methyltransferase METTL3, which regulates the NEAT1/TGF-β/Smad3 axis to slow down the rate of scar formation after breast surgery.
Collapse
Affiliation(s)
- Juan Du
- Department of Thyroid and Breast Surgery, The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University, Bengbu, 233000, Anhui, China
| | - Jincheng Wu
- Department of Thyroid and Breast Surgery, The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University, Bengbu, 233000, Anhui, China
| | - Qinqin Song
- Department of Burn and Plastic Surgery, The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University, Bengbu, 233000, Anhui, China
| | - Shuangru Li
- Department of Burn and Plastic Surgery, The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University, Bengbu, 233000, Anhui, China
| | - Youwang Hong
- Department of Burn and Plastic Surgery, The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University, Bengbu, 233000, Anhui, China
| | - Aizaz Anwar
- Department of Burn and Plastic Surgery, The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University, Bengbu, 233000, Anhui, China
| | - Quanyou Fu
- Department of Burn and Plastic Surgery, The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University, Bengbu, 233000, Anhui, China
| | - Jisong Liu
- Department of Burn and Plastic Surgery, The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University, Bengbu, 233000, Anhui, China.
| |
Collapse
|
|
6
|
Wang H, Wu S, Bai X, Pan D, Ning Y, Wang C, Guo L, Guo J, Gu Y. Mesenchymal Stem Cell-Derived Exosomes Hold Promise in the Treatment of Diabetic Foot Ulcers. Int J Nanomedicine 2025; 20:5837-5857. [PMID: 40351704 PMCID: PMC12065540 DOI: 10.2147/ijn.s516533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 04/11/2025] [Indexed: 05/14/2025] Open
Abstract
Diabetic foot ulcers (DFU) represent one of the most common side effects of diabetes, significantly impacting patients' quality of life and imposing considerable financial burdens on families and society at large. Despite advancements in therapies targeting lower limb revascularization and various medications and dressings, outcomes for patients with severe lesions remain limited. A recent breakthrough in DFU treatment stems from the development of mesenchymal stem cells (MSCs). MSCs have shown promising results in treating various diseases and skin wounds due to their ability for multidirectional differentiation and immunomodulation. Recent studies highlight that MSCs primarily repair tissue through their paracrine activities, with exosomes playing a crucial role as the main biologically active components. These exosomes transport proteins, mRNA, DNA, and other substances, facilitating DFU treatment through immunomodulation, antioxidant effects, angiogenesis promotion, endothelial cell migration and proliferation, and collagen remodeling. Mesenchymal stem cell-derived exosomes (MSC-Exo) not only deliver comparable therapeutic effects to MSCs but also mitigate adverse reactions like immune rejection associated with MSCs transplantation. This article provides an overview of DFU pathophysiology and explores the mechanisms and research progress of MSC-Exo in DFU therapy.
Collapse
Affiliation(s)
- Hui Wang
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Sensen Wu
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Xinyu Bai
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China
| | - Dikang Pan
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Yachan Ning
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Cong Wang
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Lianrui Guo
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Jianming Guo
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Yongquan Gu
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| |
Collapse
|
|
7
|
Gong S, Niu H, Jia Y, Liu M, Ren X, Zhang D, Shen J, Yang C, Lei Y, Zhao P, Lin P. Repairing Qinling Giant Panda Skin Wounds Using Adipose Mesenchymal Stem Cell-Derived Extracellular Vesicles. Animals (Basel) 2025; 15:1270. [PMID: 40362085 PMCID: PMC12070915 DOI: 10.3390/ani15091270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 04/16/2025] [Accepted: 04/28/2025] [Indexed: 05/15/2025] Open
Abstract
The Qinling giant panda has a high susceptibility to skin damage, which affects its survival. Although their healing efficacy in panda injuries remains unexplored, extracellular vesicles from adipose-derived mesenchymal stem cells (ADMSC-EVs) have shown promise in regenerative medicine. In this study, ADMSC-EVs were successfully obtained from Qinling giant pandas using ultracentrifugation, and proteomic techniques were used to analyze their composition and function. Primary skin fibroblasts from Qinling giant pandas were isolated and cultured to explore the effects of ADMSC-EVs on cell proliferation and migration. Additionally, a mouse model of skin injury was used to assess their wound healing effects. The ADMSC-EVs contained various substances, particularly proteins, with fifty unique proteins involved in transport, catabolism, and signal transduction identified. The application of ADMSC-EVs in a mouse model accelerated wound healing and promoted the regeneration of the epidermal and dermal layers. It facilitated the repair of skin appendages, including hair follicles and sebaceous glands. Additionally, ADMSC-EVs enhanced collagen deposition, stimulated angiogenesis, and reduced inflammation. Our findings confirm that ADMSC-EVs significantly improve skin healing, thus supporting the theoretical framework for the clinical use of giant panda extracellular vesicles and underscoring their potential for preserving the genetic resources of the Qinling giant panda.
Collapse
Affiliation(s)
- Suhua Gong
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (S.G.); (H.N.); (Y.J.); (M.L.); (X.R.)
| | - Hongyu Niu
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (S.G.); (H.N.); (Y.J.); (M.L.); (X.R.)
| | - Yanni Jia
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (S.G.); (H.N.); (Y.J.); (M.L.); (X.R.)
| | - Mengjie Liu
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (S.G.); (H.N.); (Y.J.); (M.L.); (X.R.)
| | - Xiaoyu Ren
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (S.G.); (H.N.); (Y.J.); (M.L.); (X.R.)
| | - Danhui Zhang
- Research Center for the Qinling Giant Panda, Rescue Base of Rare Wild Animals in Shaanxi Province, Louguantai, Xi’an 710402, China; (D.Z.); (J.S.); (Y.L.)
| | - Jiena Shen
- Research Center for the Qinling Giant Panda, Rescue Base of Rare Wild Animals in Shaanxi Province, Louguantai, Xi’an 710402, China; (D.Z.); (J.S.); (Y.L.)
| | - Chuangxue Yang
- Louguantai State Owned Ecological Experimental Forest Farm in Shaanxi Province, Zhouzhi, Xi’an 710402, China;
| | - Yinghu Lei
- Research Center for the Qinling Giant Panda, Rescue Base of Rare Wild Animals in Shaanxi Province, Louguantai, Xi’an 710402, China; (D.Z.); (J.S.); (Y.L.)
| | - Pengpeng Zhao
- Research Center for the Qinling Giant Panda, Rescue Base of Rare Wild Animals in Shaanxi Province, Louguantai, Xi’an 710402, China; (D.Z.); (J.S.); (Y.L.)
| | - Pengfei Lin
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (S.G.); (H.N.); (Y.J.); (M.L.); (X.R.)
| |
Collapse
|
|
8
|
Rong J, Li YY, Wang X, Wang JN, Song M. Non-coding RNAs in adipose-derived stem cell exosomes: Mechanisms, therapeutic potential, and challenges in wound healing. World J Stem Cells 2025; 17:102917. [PMID: 40308889 PMCID: PMC12038460 DOI: 10.4252/wjsc.v17.i4.102917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/23/2024] [Accepted: 03/21/2025] [Indexed: 04/23/2025] Open
Abstract
The treatment of complex wounds presents a significant clinical challenge due to the limited availability of standardized therapeutic options. Adipose-derived stem cell exosomes (ADSC-Exos) are promising for their capabilities to enhance angiogenesis, mitigate oxidative stress, modulate inflammatory pathways, support skin cell regeneration, and promote epithelialization. These exosomes deliver non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, which facilitate collagen remodeling, reduce scar formation, and expedite wound healing. This study reviews the mechanisms, therapeutic roles, and challenges of non-coding RNA-loaded ADSC-Exos in wound healing and identifies critical directions for future research. It aims to provide insights for researchers into the potential mechanisms and clinical applications of ADSC-Exos non-coding RNAs in wound healing.
Collapse
Affiliation(s)
- Jian Rong
- Department of Burns and Plastic Surgery, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Plateau Medicine, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Yao-Yao Li
- Department of Burns and Plastic Surgery, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Plateau Medicine, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Xin Wang
- Department of Burns and Plastic Surgery, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Plateau Medicine, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Jia-Ning Wang
- Department of Burns and Plastic Surgery, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Plateau Medicine, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Mei Song
- Department of Burns and Plastic Surgery, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Plateau Medicine, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China.
| |
Collapse
|
|
9
|
Eerdekens H, Pirlet E, Willems S, Bronckaers A, Pincela Lins PM. Extracellular vesicles: innovative cell-free solutions for wound repair. Front Bioeng Biotechnol 2025; 13:1571461. [PMID: 40248643 PMCID: PMC12003306 DOI: 10.3389/fbioe.2025.1571461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Accepted: 03/17/2025] [Indexed: 04/19/2025] Open
Abstract
Chronic non-healing wounds are often associated with conditions such as diabetes and peripheral vascular disease, pose significant medical and socioeconomic challenges. Cell-based therapies have shown promise in promoting wound healing but have major drawbacks such as immunogenicity and tumor formation. As a result, recent research has shifted to the potential of extracellular vesicles (EVs) derived from these cells. EVs are nanosized lipid bilayer vesicles, naturally produced by all cell types, which facilitate intercellular communication and carry bioactive molecules, offering advantages such as low immunogenicity, negligible toxicity and the potential to be re-engineered. Recent evidence recognizes that during wound healing EVs are released from a wide range of cells including immune cells, skin cells, epithelial cells and platelets and they actively participate in wound repair. This review comprehensively summarizes the latest research on the function of EVs from endogenous cell types during the different phases of wound healing, thereby presenting interesting therapeutic targets. Additionally, it gives a critical overview of the current status of mesenchymal stem cell-derived EVs in wound treatment highlighting their tremendous therapeutic potential as a non-cellular of-the-shelf alternative in wound care.
Collapse
Affiliation(s)
- Hanne Eerdekens
- Hasselt University, Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium
| | - Elke Pirlet
- Hasselt University, Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium
| | - Sarah Willems
- Hasselt University, Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium
| | - Annelies Bronckaers
- Hasselt University, Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium
| | - Paula M. Pincela Lins
- Hasselt University, Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium
- Flemish Institute for Technological Research (VITO), Environmental Intelligence Unit, Mol, Belgium
| |
Collapse
|
|
10
|
Mahmoud RH, Peterson E, Badiavas EV, Kaminer M, Eber AE. Exosomes: A Comprehensive Review for the Practicing Dermatologist. THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY 2025; 18:33-40. [PMID: 40256340 PMCID: PMC12007658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 04/22/2025]
Abstract
This clinical review examines what is known about exosomes and their applicability to aesthetic dermatology. Exosomes are extracellular vesicles with crucial roles in intercellular communication. Their biogenesis is complex and not completely understood, but they are generally formed intracellularly in the endosomal compartment of a cell or through direct plasma membrane release. Several mechanisms of exosome uptake have been described and are dependent on the molecular characteristics of the recipient cell and exosome membrane. Furthermore, there are a multitude of exosome isolation and characterization techniques, each with their own potential advantages and disadvantages. Exosomes have demonstrated promise in preclinical models across various domains of aesthetic dermatology, including as anti-aging and anti-inflammatory therapies and as therapeutics for wound healing, scar reduction, and hair regeneration. However, clinical studies are lacking, and there are substantial safety concerns, such as the potential risk of infections, unwanted inflammatory response, and promotion of malignancy. Further research is needed to develop more precise analytical techniques to better understand the composition of exosomes, their safety profiles, and their potential applications to patient care.
Collapse
Affiliation(s)
- Rami H. Mahmoud
- Mr. Mahmoud, Drs. Peterson, Badiavas, and Eber are with the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery at the University of Miami Miller School of Medicine in Miami, Florida
| | - Erik Peterson
- Mr. Mahmoud, Drs. Peterson, Badiavas, and Eber are with the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery at the University of Miami Miller School of Medicine in Miami, Florida
| | - Evangelos V. Badiavas
- Mr. Mahmoud, Drs. Peterson, Badiavas, and Eber are with the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery at the University of Miami Miller School of Medicine in Miami, Florida
| | - Michael Kaminer
- Dr. Kaminer is with the Department of Dermatology at Yale School of Medicine in New Haven, Connecticut; the Department of Dermatology at The Warren Alpert Medical School of Brown University in Providence, Rhode Island; and Skincare Physicians in Chestnut Hill, Massachusetts
| | - Ariel E. Eber
- Mr. Mahmoud, Drs. Peterson, Badiavas, and Eber are with the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery at the University of Miami Miller School of Medicine in Miami, Florida
| |
Collapse
|
|
11
|
Pamulang YV, Oontawee S, Rodprasert W, Padeta I, Sa-Ard-Lam N, Mahanonda R, Osathanon T, Somparn P, Pisitkun T, Torsahakul C, Sawangmake C. Potential upscaling protocol establishment and wound healing bioactivity screening of exosomes isolated from canine adipose-derived mesenchymal stem cells. Sci Rep 2025; 15:10617. [PMID: 40148423 PMCID: PMC11950392 DOI: 10.1038/s41598-025-93219-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 03/05/2025] [Indexed: 03/29/2025] Open
Abstract
Mesenchymal stem cell-derived exosomes exhibit promising potential in tissue regeneration. Recent studies highlight its significant therapeutic potential in various stages of wound healing. However, the clinical translation of exosome-based therapy was hindered due to issues regarding low productivity and the lack of efficient production protocol to obtain a clinically relevant exosome quantity. Therefore, this study established a potential upscaling protocol to produce exosomes derived from canine adipose-derived mesenchymal stem cells (cAD-MSCs) and explored its potential for wound treatment. The potential upscaling protocol, termed VSCBIC-3-3D, was carried out using VSCBIC-3 in-house serum-free exosome-collecting solution in a three-dimensional (3D) culture system followed by the tangential flow filtration (TFF) isolation. Our findings suggest that culturing cAD-MSCs with VSCBIC-3 maintained cell morphology and viability. Compared to conventional two-dimensional (2D) protocols, The potential upscaling protocol increased exosome yield and concentration in conditioned medium by 2.4-fold and 3.2-fold, respectively. The quality assessment revealed enhanced purity and bioactivity of exosomes produced using the VSCBIC-3-3D protocol. In addition, the cAD-MSCs-derived exosomes were shown to significantly improve fibroblast migration, proliferation, and wound healing-related gene expression in vitro. This study collectively demonstrates that potential upscaling protocol establishment allowed robust production of exosomes from cAD-MSCs, which exhibit therapeutic potential for wound healing in vitro.
Collapse
Affiliation(s)
- Yudith Violetta Pamulang
- The International Graduate Program of Veterinary Science and Technology (VST), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
- Center of Excellence for Veterinary Clinical Stem Cells and Bioengineering, Chulalongkorn University, Bangkok, 10330, Thailand
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Saranyou Oontawee
- Center of Excellence for Veterinary Clinical Stem Cells and Bioengineering, Chulalongkorn University, Bangkok, 10330, Thailand
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Watchareewan Rodprasert
- Center of Excellence for Veterinary Clinical Stem Cells and Bioengineering, Chulalongkorn University, Bangkok, 10330, Thailand
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Irma Padeta
- The International Graduate Program of Veterinary Science and Technology (VST), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
- Center of Excellence for Veterinary Clinical Stem Cells and Bioengineering, Chulalongkorn University, Bangkok, 10330, Thailand
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Noppadol Sa-Ard-Lam
- Immunology Research Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
- Center of Excellence in Periodontal Disease and Dental Implant, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Rangsini Mahanonda
- Immunology Research Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
- Center of Excellence in Periodontal Disease and Dental Implant, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Thanaphum Osathanon
- Dental Stem Cell Biology Research Unit, Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
- Center of Excellence in Regenerative Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Poorichaya Somparn
- Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Trairak Pisitkun
- Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Chutirat Torsahakul
- Center of Excellence for Veterinary Clinical Stem Cells and Bioengineering, Chulalongkorn University, Bangkok, 10330, Thailand
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
- Department of Veterinary Medicine, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Chenphop Sawangmake
- Center of Excellence for Veterinary Clinical Stem Cells and Bioengineering, Chulalongkorn University, Bangkok, 10330, Thailand.
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
- Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
| |
Collapse
|
|
12
|
Li J, Wang Z, Wei Y, Li W, He M, Kang J, Xu J, Liu D. Advances in Tracing Techniques: Mapping the Trajectory of Mesenchymal Stem-Cell-Derived Extracellular Vesicles. CHEMICAL & BIOMEDICAL IMAGING 2025; 3:137-168. [PMID: 40151822 PMCID: PMC11938168 DOI: 10.1021/cbmi.4c00085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 12/30/2024] [Accepted: 01/03/2025] [Indexed: 03/29/2025]
Abstract
Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are nanoscale lipid bilayer vesicles secreted by mesenchymal stem cells. They inherit the parent cell's attributes, facilitating tissue repair and regeneration, promoting angiogenesis, and modulating the immune response, while offering advantages like reduced immunogenicity, straightforward administration, and enhanced stability for long-term storage. These characteristics elevate MSC-EVs as highly promising in cell-free therapy with notable clinical potential. It is critical to delve into their pharmacokinetics and thoroughly elucidate their intracellular and in vivo trajectories. A detailed summary and evaluation of existing tracing strategies are needed to establish standardized protocols. Here, we have summarized and anticipated the research progress of MSC-EVs in various biomedical imaging techniques, including fluorescence imaging, bioluminescence imaging, nuclear imaging (PET, SPECT), tomographic imaging (CT, MRI), and photoacoustic imaging. The challenges and prospects of MSC-EV tracing strategies, with particular emphasis on clinical translation, have been analyzed, with promising solutions proposed.
Collapse
Affiliation(s)
- Jingqi Li
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Zhaoyu Wang
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Yongchun Wei
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Wenshuai Li
- State
Key Laboratory for Crop Stress Resistance and High-Efficiency Production,
Shaanxi Key Laboratory of Agricultural and Environmental Microbiology,
College of Life Sciences, Northwest A&F
University, Yangling, Shaanxi 712100, China
| | - Mingzhu He
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Jingjing Kang
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Jia Xu
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Dingbin Liu
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| |
Collapse
|
|
13
|
Su X, Wang H, Li Q, Chen Z. Extracellular Vesicles: A Review of Their Therapeutic Potentials, Sources, Biodistribution, and Administration Routes. Int J Nanomedicine 2025; 20:3175-3199. [PMID: 40098717 PMCID: PMC11913029 DOI: 10.2147/ijn.s502591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 02/18/2025] [Indexed: 03/19/2025] Open
Abstract
Extracellular vesicles (EVs) participate in intercellular communication and play an essential role in physiological and pathological processes. In recent years, EVs have garnered significant attention as cell-free therapeutic alternatives, vectors for drug and gene delivery, biomarkers for disease diagnosis and prognosis, vaccine development, and nutraceuticals. The biodistribution of EVs critically influences their efficacy and toxicity. Therefore, this review aims to discuss the main factors influencing the biodistribution of unmodified EVs, highlighting their distribution patterns, advantages, limitations, and applications under different routes of administration. In addition, we provide a comprehensive discussion of the currently available sources of EVs and summarize the current status of the therapeutic potentials of EVs. By optimizing administration routes and selecting appropriate EV sources, we aim to offer valuable insights to enhance the delivery efficiency and therapeutic efficacy of EVs to target tissues.
Collapse
Affiliation(s)
- Xiaorong Su
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
| | - Hongxiang Wang
- Department of Hematology, Key Laboratory for Molecular Diagnosis of Hubei Province, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People’s Republic of China
| | - Qiubai Li
- Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
- Hubei Engineering Research Center for Application of Extracellular Vesicle, Hubei University of Science and Technology, Xianning, 437100, People’s Republic of China
| | - Zhichao Chen
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
| |
Collapse
|
|
14
|
Camacho-Cardenosa M, Pulido-Escribano V, Estrella-Guisado G, Dorado G, Herrera-Martínez AD, Gálvez-Moreno MÁ, Casado-Díaz A. Bioprinted Hydrogels as Vehicles for the Application of Extracellular Vesicles in Regenerative Medicine. Gels 2025; 11:191. [PMID: 40136896 PMCID: PMC11941778 DOI: 10.3390/gels11030191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 03/06/2025] [Accepted: 03/07/2025] [Indexed: 03/27/2025] Open
Abstract
Three-dimensional bioprinting is a new advance in tissue engineering and regenerative medicine. Bioprinting allows manufacturing three-dimensional (3D) structures that mimic tissues or organs. The bioinks used are mainly made of natural or synthetic polymers that must be biocompatible, printable, and biodegradable. These bioinks may incorporate progenitor cells, favoring graft implantation and regeneration of injured tissues. However, the natures of biomaterials, bioprinting processes, a lack of vascularization, and immune responses are factors that limit the viability and functionality of implanted cells and the regeneration of damaged tissues. These limitations can be addressed by incorporating extracellular vesicles (EV) into bioinks. Indeed, EV from progenitor cells may have regenerative capacities, being similar to those of their source cells. Therefore, their combinations with biomaterials can be used in cell-free therapies. Likewise, they can complement the manufacture of bioinks by increasing the viability, differentiation, and regenerative ability of incorporated cells. Thus, the main objective of this review is to show how the use of 3D bioprinting technology can be used for the application of EV in regenerative medicine by incorporating these nanovesicles into hydrogels used as bioinks. To this end, the latest advances derived from in vitro and in vivo studies have been described. Together, these studies show the high therapeutic potential of this strategy in regenerative medicine.
Collapse
Affiliation(s)
- Marta Camacho-Cardenosa
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain; (M.C.-C.); (V.P.-E.); (G.E.-G.); (A.D.H.-M.)
| | - Victoria Pulido-Escribano
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain; (M.C.-C.); (V.P.-E.); (G.E.-G.); (A.D.H.-M.)
| | - Guadalupe Estrella-Guisado
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain; (M.C.-C.); (V.P.-E.); (G.E.-G.); (A.D.H.-M.)
| | - Gabriel Dorado
- Departamento Bioquímica y Biología Molecular, Campus Rabanales C6-1-E17, Campus de Excelencia Internacional Agroalimentario (ceiA3), Universidad de Córdoba, 14071 Córdoba, Spain;
- CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), 14004 Córdoba, Spain
| | - Aura D. Herrera-Martínez
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain; (M.C.-C.); (V.P.-E.); (G.E.-G.); (A.D.H.-M.)
| | - María Ángeles Gálvez-Moreno
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain; (M.C.-C.); (V.P.-E.); (G.E.-G.); (A.D.H.-M.)
| | - Antonio Casado-Díaz
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain; (M.C.-C.); (V.P.-E.); (G.E.-G.); (A.D.H.-M.)
- CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), 14004 Córdoba, Spain
| |
Collapse
|
|
15
|
Wang F, Guo SQ, Su TH, Tian XJ, Wen WJ, Pan HP, Wang XF, Zhang W, Zhong JL, Dong ZS, Luo P. Bioactive-Enriched Nanovesicles from American Cockroaches Enhance Wound Healing by Promoting Angiogenesis. ACS APPLIED MATERIALS & INTERFACES 2025; 17:13565-13576. [PMID: 39988799 DOI: 10.1021/acsami.4c21532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Abstract
Skin trauma often results from pain, swelling, and scarring and can significantly interfere with daily activities. Extracts from the American cockroach, a rapidly reproducing insect, have been recognized for therapeutic properties in wound management. Traditional extraction methods use solvents such as ethanol to obtain the active compounds, but these methods may compromise the intrinsic biological properties of American cockroach extracts. In this study, we investigated the use of nanovesicles isolated from fresh American cockroaches in skin wound treatment and focused on their biological characteristics and therapeutic efficacy. Fresh and dried American cockroach nanovesicles (F-ACNVs and D-ACNVs, respectively) were procured via ultrahigh-speed centrifugation. We found that F-ACNVs exhibited superior cell proliferation-promoting activity. By employing metabolomics, proteomics, and long noncoding RNA (lncRNA) omics, we identified a rich repertoire of metabolites, proteins, and lncRNAs within F-ACNVs. In vitro and in vivo experiments demonstrated that F-ACNVs significantly enhanced the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and human skin keratinocytes (HACATs) as well as the repair of skin mechanical trauma. These effects may be mediated through the activation of angiogenic signaling pathways. Our research introduces a novel therapeutic strategy for treating skin trauma and offers insight into the medicinal potential of insects such as the American cockroach while emphasizing the importance of preserving the intrinsic biological properties of insects for optimal therapeutic outcomes.
Collapse
Affiliation(s)
- Fang Wang
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Shi-Qi Guo
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Tao-Hong Su
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Xiu-Jia Tian
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Wei-Jie Wen
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Hua-Ping Pan
- Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Xiao-Fen Wang
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Wen Zhang
- Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Jing-Li Zhong
- Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Zi-Shu Dong
- Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Ping Luo
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| |
Collapse
|
|
16
|
Li L, Yao Z, Salimian KJ, Kong J, Zaheer A, Parian A, Gearhart SL, Mao HQ, Selaru FM. Extracellular Vesicles Delivered by a Nanofiber-Hydrogel Composite Enhance Healing In Vivo in a Model of Crohn's Disease Perianal Fistula. Adv Healthc Mater 2025; 14:e2402292. [PMID: 39240055 PMCID: PMC11882933 DOI: 10.1002/adhm.202402292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 08/24/2024] [Indexed: 09/07/2024]
Abstract
Perianal fistulas represent a common, aggressive, and disabling complication of Crohn's disease (CD). Despite recent drug developments, novel surgical interventions as well as multidisciplinary treatment approaches, the outcome is dismal, with >50% therapy failure rates. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) offer potential therapeutic benefits for treating fistulizing CD, due to the pro-regenerative paracrine signals. However, a significant obstacle to clinical translation of EV-based therapy is the rapid clearance and short half-life of EVs in vivo. Here, an injectable, biodegradable nanofiber-hydrogel composite (NHC) microgel matrix that serves as a carrier to deliver MSC-derived EVs to a rat model of CD perianal fistula (PAF) is reported. It is found that EV-loaded NHC (EV-NHC) yields the best fistula healing when compared to other treatment arms. The MRI assessment reveals that the EV-NHC reduces inflammation at the fistula site and promotes tissue healing. The enhanced therapeutic outcomes are contributed by extended local retention and sustained release of EVs by NHC. In addition, the EV-NHC effectively reduces inflammation at the fistula site and promotes tissue healing and regeneration via macrophage polarization and neo-vascularization. This EV-NHC platform provides an off-the-shelf solution that facilitates its clinical translation.
Collapse
Affiliation(s)
- Ling Li
- Division of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University; Baltimore, Maryland, USA
| | - Zhicheng Yao
- Institute for NanoBioTechnology, Johns Hopkins University; Baltimore, Maryland, USA
- Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University; Baltimore, Maryland, USA
- Translational Tissue Engineering Center, Johns Hopkins University School of Medicine; Baltimore, Maryland, USA
| | - Kevan J. Salimian
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jiayuan Kong
- Institute for NanoBioTechnology, Johns Hopkins University; Baltimore, Maryland, USA
- Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University; Baltimore, Maryland, USA
- Translational Tissue Engineering Center, Johns Hopkins University School of Medicine; Baltimore, Maryland, USA
| | - Atif Zaheer
- Department of Radiology & Radiological Sciences, School of Medicine, Johns Hopkins University; Baltimore, Maryland, USA
| | - Alyssa Parian
- Division of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University; Baltimore, Maryland, USA
| | - Susan L. Gearhart
- Division of Colorectal Surgery, Department of Surgery, Johns Hopkins University School of Medicine; Baltimore, Maryland, USA
| | - Hai-Quan Mao
- Institute for NanoBioTechnology, Johns Hopkins University; Baltimore, Maryland, USA
- Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University; Baltimore, Maryland, USA
- Translational Tissue Engineering Center, Johns Hopkins University School of Medicine; Baltimore, Maryland, USA
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine; Baltimore, Maryland, USA
| | - Florin M. Selaru
- Division of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University; Baltimore, Maryland, USA
- Institute for NanoBioTechnology, Johns Hopkins University; Baltimore, Maryland, USA
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine; Baltimore, Maryland, USA
- Department of Oncology, Sidney Kimmel Cancer Center, School of Medicine, Johns Hopkins University; Baltimore, Maryland, USA
| |
Collapse
|
|
17
|
Poorkazem H, Saber M, Moradmand A, Yakhkeshi S, Seydi H, Hajizadeh-Saffar E, Shekari F, Hassani SN. Comparative effects of various extracellular vesicle subpopulations derived from clonal mesenchymal stromal cells on cultured fibroblasts in wound healing-related process. Int J Biochem Cell Biol 2025; 180:106737. [PMID: 39828140 DOI: 10.1016/j.biocel.2025.106737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/25/2024] [Accepted: 01/09/2025] [Indexed: 01/22/2025]
Abstract
INTRODUCTION Non-healing wounds pose significant challenges and require effective therapeutic interventions. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents in tissue regeneration. However, the functional differences between different subpopulations of EVs in wound healing remain understudied. This study aimed to evaluate the effects of two distinct subpopulations of clonal mesenchymal stromal cells (cMSC)-derived EVs (cMSC-EVs), namely 20 K and 110K-cMSC-EVs, primarily on in vitro wound healing process, providing fast and cost-effective alternatives to animal models. METHODS In vitro assays were conducted to compare the effects of 20 K and 110K-cMSC-EVs, isolated through high-speed centrifugation and differential ultracentrifugation, respectively. For evaluation the main mechanisms of wound healing, including cell proliferation, cell migration, angiogenesis, and contraction. Human dermal fibroblasts (HDF) were considered as the main cells for analysis of these procedures. Moreover, gene expression analysis was performed to assess the impact of these EV subpopulations on the related process of wound healing on HDF. RESULTS The results demonstrated that both 20 K and 110K-cMSC-EVs exhibited beneficial effects on cell proliferation, cell migration, angiogenesis, and gel contraction. RT-qPCR revealed that both EV types downregulated interleukin 6 (IL6), induced proliferation by upregulating proliferating cell nuclear antigen (PCNA), and regulated remodeling by upregulating matrix metallopeptidase 1 (MMP1) and downregulating collagen type 1 (COL1). DISCUSSION This study highlights the effects of both 20 K and 110K-cMSC-EVs on the potency of HDFs in wound healing-related process. As the notable finding, 20K-cMSC-EVs offer a more feasible and cost-effective subpopulation for isolation and follow the GMP standard, recommended to utilize this fraction for therapeutic application.
Collapse
Affiliation(s)
- Hedie Poorkazem
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran
| | - Maryam Saber
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Azadeh Moradmand
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Saeed Yakhkeshi
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Homeyra Seydi
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Ensiyeh Hajizadeh-Saffar
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Faezeh Shekari
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
| | - Seyedeh-Nafiseh Hassani
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
| |
Collapse
|
|
18
|
Xu L, Liu D, Yun HL, Zhang W, Ren L, Li WW, Han C. Effect of adipose-derived stem cells exosomes cross-linked chitosan-αβ-glycerophosphate thermosensitive hydrogel on deep burn wounds. World J Stem Cells 2025; 17:102091. [DOI: 10.4252/wjsc.v17.i2.102091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/16/2024] [Accepted: 02/07/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Burn wound management is challenging, and while mesenchymal stem cell-derived exosomes show therapeutic potential, optimal delivery methods are unclear.
AIM To study chitosan (CS)-αβ-glycerophosphate (CS-αβ-GP) hydrogel crosslinked with adipose-derived stem cell exosomes (ASC-Exos) for healing deep burn injuries.
METHODS Rats with deep burn injuries were divided into the CS + ASCs-Exos group, the ASCs-Exos group, the CS group, and the control group. The healing rates on days 4, 7, and 14 after treatment were analyzed using ImageJ software. On day 14, the tissues were stained with hematoxylin and eosin staining, Masson’s trichrome staining, and immunohistochemical analysis to evaluate tumor necrosis factor α, interleukin-6 (IL-6), IL-1α, IL-10, transforming growth factor β, and epidermal growth factor. The mRNA levels of IL-1α, CD86, C-C motif chemokine ligand 22, and CD163 were evaluated through quantitative polymerase chain reaction.
RESULTS The CS + ASC-Exos group exhibited enhanced healing, reduced lymphocyte infiltration, blood vessels, and muscle fiber distribution. Increased IL-10, transforming growth factor β, and epidermal growth factor and decreased tumor necrosis factor α, IL-1α, and IL-6 expression were observed. Quantitative polymerase chain reaction revealed reduced IL-1α and CD86 and increased C-C motif chemokine ligand 22 and CD163 expression. Protein analysis showed downregulation of phosphorylated inhibitor of kappa Balpha and P65 in the nuclear factor κB (NF-κB) pathway. ASC-Exos crosslinked with CS-αβ-GP hydrogel demonstrates superior effects in anti-inflammation, wound healing promotion, and promotion of M1 macrophage transformation to M2 macrophage by blocking the NF-κB pathway compared to ASC-Exos alone.
CONCLUSION Our research demonstrates that the ASC-Exos cross-linked CS-αβ-GP hydrogel represents an advanced therapeutic approach for treating deep burn wounds. It has anti-inflammatory effects, promotes wound healing, and facilitates the transition of M1 macrophages to M2 macrophages by blocking the NF-κB pathway.
Collapse
Affiliation(s)
- Lei Xu
- Department of Pathology, General Hospital of the Western Theater Command, Chengdu 610038, Sichuan Province, China
| | - Dan Liu
- Department of Endocrinology, General Hospital of the Western Theater Command, Chengdu 610038, Sichuan Province, China
| | - Hai-Long Yun
- Department of Pathology, General Hospital of the Western Theater Command, Chengdu 610038, Sichuan Province, China
| | - Wei Zhang
- Department of Endocrinology, General Hospital of the Western Theater Command, Chengdu 610038, Sichuan Province, China
| | - Li Ren
- Department of Endocrinology, General Hospital of the Western Theater Command, Chengdu 610038, Sichuan Province, China
| | - Wen-Wen Li
- Department of Endocrinology, General Hospital of the Western Theater Command, Chengdu 610038, Sichuan Province, China
| | - Chuan Han
- Department of Endocrinology, General Hospital of the Western Theater Command, Chengdu 610038, Sichuan Province, China
| |
Collapse
|
|
19
|
Fang C, Zeng Z, Ye J, Ni B, Zou J, Zhang G. Progress of mesenchymal stem cells affecting extracellular matrix metabolism in the treatment of female stress urinary incontinence. Stem Cell Res Ther 2025; 16:95. [PMID: 40001265 PMCID: PMC11863768 DOI: 10.1186/s13287-025-04220-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 02/11/2025] [Indexed: 02/27/2025] Open
Abstract
Stress urinary incontinence (SUI) is a prevalent pelvic floor dysfunction in women post-pregnancy. Currently, conservative treatment options have low success rates, while surgical interventions often result in multiple complications. The altered state of the extracellular matrix (ECM) is a pivotal factor in the onset of various diseases and likely plays a significant role in the pathogenesis of SUI, particularly through changes in collagen and elastin levels. Recent advances in mesenchymal stem cells (MSCs) therapy have shown considerable promise in treating SUI by modulating ECM remodeling, thereby enhancing the supportive tissues of the female pelvic floor. MSCs exhibit substantial potential in enhancing urethral sphincter function, modulating connective tissue architecture, and stimulating fibroblast activity. They play a pivotal role in the reconstruction and functional recovery of the ECM by influencing various signaling pathways, including TGF-β/SMAD, JAK/STAT, Wnt/β-catenin, PI3K/AKT, and ERK/MAPK. We have reviewed the advancements in MSC-mediated ECM metabolism in SUI and, by integrating the functions of ECM in other diseases and how MSCs can ameliorate conditions through their impact on ECM metabolism, we have projected the future trajectory of SUI treatment development.
Collapse
Affiliation(s)
- Chunyun Fang
- Department of Obstetrics and Gynecology, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Zitao Zeng
- First Clinical College of Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Junsong Ye
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Bin Ni
- Department of Pharmacy, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Junrong Zou
- Department of Urology, Institute of Urology, First Affiliated Hospital of Gannan Medical University, Jiangxi Engineering Technology Research Center of Calculi Prevention, Gannan Medical University, No. 128, Jinling Road, Zhanggong District, Ganzhou, Jiangxi, 341000, China
| | - Guoxi Zhang
- Department of Urology, Institute of Urology, First Affiliated Hospital of Gannan Medical University, Jiangxi Engineering Technology Research Center of Calculi Prevention, Gannan Medical University, No. 128, Jinling Road, Zhanggong District, Ganzhou, Jiangxi, 341000, China.
| |
Collapse
|
|
20
|
Jin W, Li Y, Yu M, Ren D, Han C, Guo S. Advances of exosomes in diabetic wound healing. BURNS & TRAUMA 2025; 13:tkae078. [PMID: 39980588 PMCID: PMC11836438 DOI: 10.1093/burnst/tkae078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 06/11/2024] [Accepted: 11/09/2024] [Indexed: 02/22/2025]
Abstract
Poor wound healing is a refractory process that places an enormous medical and financial burden on diabetic patients. Exosomes have recently been recognized as crucial players in the healing of diabetic lesions. They have excellent stability, homing effects, biocompatibility, and reduced immunogenicity as novel cell-free therapies. In addition to transporting cargos to target cells to enhance intercellular communication, exosomes are beneficial in nearly every phase of diabetic wound healing. They participate in modulating the inflammatory response, accelerating proliferation and reepithelization, increasing angiogenesis, and regulating extracellular matrix remodeling. Accumulating evidence indicates that hydrogels or dressings in conjunction with exosomes can prolong the duration of exosome residency in diabetic wounds. This review provides an overview of the mechanisms, delivery, clinical application, engineering, and existing challenges of the use of exosomes in diabetic wound repair. We also propose future directions for biomaterials incorporating exosomes: 2D or 3D scaffolds, biomaterials loaded with wound healing-promoting gases, intelligent biomaterials, and the prospect of systematic application of exosomes. These findings may might shed light on future treatments and enlighten some studies to improve quality of life among diabetes patients.
Collapse
Affiliation(s)
- Weixue Jin
- Department of Plastic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, 1511 Jiang Hong Road, Binjiang District, Hangzhou 310009, Zhejiang, China
| | - Yi Li
- Department of Plastic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, 1511 Jiang Hong Road, Binjiang District, Hangzhou 310009, Zhejiang, China
| | - Meirong Yu
- Center for Basic and Translational Research, Second Affiliated Hospital Zhejiang University School of Medicine, 88 Jie Fang Road, Shangcheng District, Hangzhou 310009, Zhejiang, China
| | - Danyang Ren
- Department of Plastic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, 1511 Jiang Hong Road, Binjiang District, Hangzhou 310009, Zhejiang, China
| | - Chunmao Han
- Department of Burns and Wound Repair, Second Affiliated Hospital Zhejiang University School of Medicine, 88 Jie Fang Road, Shangcheng District, Hangzhou 310009, Zhejiang, China
- Zhejiang Key Laboratory of Trauma, Burn, and Medical Rescue, 88 Jie Fang Road, Shangcheng District, Hangzhou 310009, Zhejiang, China
| | - Songxue Guo
- Department of Plastic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, 1511 Jiang Hong Road, Binjiang District, Hangzhou 310009, Zhejiang, China
- Zhejiang Key Laboratory of Trauma, Burn, and Medical Rescue, 88 Jie Fang Road, Shangcheng District, Hangzhou 310009, Zhejiang, China
| |
Collapse
|
|
21
|
Liu J, Jiang Y, Chen X, Wei X, Wang X, Yang Z, Yang J, Zhang J, Peng Y, Lin C, Chen Q, Yu G, Chen Y, Wei Q, Zheng X, Zheng S. Adipose stem cells prevent esophageal strictures after extensive endoscopic submucosal dissection - experimental research. Int J Surg 2025; 111:1836-1846. [PMID: 39693486 DOI: 10.1097/js9.0000000000002148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 11/06/2024] [Indexed: 12/20/2024]
Abstract
BACKGROUND AND AIMS Endoscopic submucosal dissection (ESD) is a pivotal technique for excision of early-stage esophageal tumors. However, its primary complication, postoperative esophageal stricture, is a significant challenge owing to the absence of effective preventive measures. Adipose-derived stem cells (ADSCs) have emerged as a promising treatment modality to address this concern. In this study, we aimed to investigate, for the first time, the efficacy of allogenic ADSC injections in preventing esophageal stenosis after ESD. METHODS We administered allogeneic ADSC injections (same-species but different individual) to a porcine model of ESD as a way to observe the role of ADSC in preventing esophageal stricture. We also co-cultured rats' ADSCs with rats' esophageal fibroblasts and esophageal mucosal epithelial cells to investigate the mechanism. RESULTS ADSCs notably facilitated epithelial-mesenchymal transition of epithelial cells. Furthermore, ADSC-conditioned medium exhibited a substantial inhibitory effect on fibroblast proliferation and migration, which was mediated by the transforming growth factor-beta pathway. CONCLUSIONS Our findings underscore the potential of ADSC injections as a promising therapeutic intervention to enhance recovery and prevent post-ESD complications.
Collapse
Affiliation(s)
- Jie Liu
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Yuting Jiang
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Xianzeng Chen
- Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Anesthesiology, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Xujin Wei
- The Graduate School of Fujian Medical University, Fuzhou, China
| | - Xiangyu Wang
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Zeliang Yang
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Jie Yang
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Jianhui Zhang
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Yunyi Peng
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Caihao Lin
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Qilin Chen
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Genmiao Yu
- Department of Plastic Surgery and Burns, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Plastic Surgery and Burns, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Yangyang Chen
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Qingqing Wei
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Xiaoling Zheng
- Department of Endoscopy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Endoscopy, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Shengwu Zheng
- Department of Plastic Surgery and Burns, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
- Department of Plastic Surgery and Burns, Fujian Provincial Hospital, Fuzhou, Fujian, China
| |
Collapse
|
|
22
|
Wu X, Yuan P, Wei N, Ma C, Fu M, Wu W. Extracellular vesicles derived from "serum and glucose" deprived HUCMSCs promoted skin wound healing through enhanced angiogenesis. Mol Cell Biochem 2025; 480:1255-1273. [PMID: 38967721 DOI: 10.1007/s11010-024-05058-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 06/29/2024] [Indexed: 07/06/2024]
Abstract
Extracellular vesicles (EVs) produced from MSCs were currently considered as a novel therapeutic agent for skin tissue regeneration and repair. Preconditioning stem cells may activate more molecular pathways and release more bioactive agents. In this study, we obtained EVs from normal (N-EVs) and serum- and glucose-deprived (SGD-EVs) human umbilical cord mesenchymal stem cells (HUCMSCs), and showed that SGD-EVs promoted the migration, proliferation, and tube formation of HUVECs in vitro. In vivo experiments utilizing a rat model show that both N-EVs and SGD-EVs boosted angiogenesis of skin defects and accelerated skin wound healing, while treating wounds with SGD-EVs led to faster skin healing and enhanced angiogenesis. miRNA sequencing showed that miR-29a-3p was abundant in SGD-EVs, and overexpressing miR-29a-3p enhanced the angiogenic ability of HUVECs, while inhibiting miR-29a-3p presented the opposite effect. Further studies demonstrated that miR-29a-3p directly targeted CTNNBIP1, which mediated angiogenesis of HUCMSCs-derived EVs through inhibiting CTNNBIP1 to activate Wnt/β-catenin signaling pathway. Taken together, these findings suggested that SGD-EVs promote angiogenesis via transferring miR-29a-3p, and activation of Wnt/β-catenin signaling pathway played a crucial role in SGD-EVs-induced VEGFA production during wound angiogenesis. Our results offered a new avenue for modifying EVs to enhance tissue angiogenesis and augment its role in skin repair.
Collapse
Affiliation(s)
- Xiaopeng Wu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral & Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, 145 Changle West Road, Xincheng District, Xi'an, 710032, Shaanxi, China
- College of Life Science, Northwest University, Xi'an, 710069, China
| | - Pingping Yuan
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral & Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, 145 Changle West Road, Xincheng District, Xi'an, 710032, Shaanxi, China
| | - Na Wei
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral & Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, 145 Changle West Road, Xincheng District, Xi'an, 710032, Shaanxi, China
- College of Life Science, Northwest University, Xi'an, 710069, China
| | - Chaoqun Ma
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral & Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, 145 Changle West Road, Xincheng District, Xi'an, 710032, Shaanxi, China
| | - Mingdi Fu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral & Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, 145 Changle West Road, Xincheng District, Xi'an, 710032, Shaanxi, China
| | - Wei Wu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral & Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, 145 Changle West Road, Xincheng District, Xi'an, 710032, Shaanxi, China.
| |
Collapse
|
|
23
|
Tissot FS, Estrach S, Seguin L, Cailleteau L, Levy A, Aberdam D, Féral CC. Functional transfer of integrin co-receptor CD98hc by small extracellular vesicles improves wound healing in vivo. Matrix Biol 2025; 135:99-105. [PMID: 39674554 DOI: 10.1016/j.matbio.2024.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 12/11/2024] [Accepted: 12/11/2024] [Indexed: 12/16/2024]
Abstract
Extracellular vesicles (EVs) mediate intercellular communication. EVs are composed of a lipid bilayer and contain cytosolic proteins and RNAs. Studies highlight EVs striking functions in cell-cell crosstalk. Here, we found that small EVs can transfer functional signaling molecules through their lipid bilayer and participate in skin homeostasis. We identified a transmembrane protein CD98hc (a.k.a. SLC3A2), an integrin co-receptor (Itgb1 and Itgb3), implicated in epidermis homeostasis via its capacity in regulating extracellular matrix, as an important mediator of EV-based intercellular communication in vivo. We first demonstrated that healthy dermal fibroblasts produced and secreted EVs bearing characteristic of exosome-like small EVs (sEVs). We show that CD98hc, Itgb1 co-receptor, is present at the surface of sEVs, transferred and stabilized at the plasma membrane. The transferred complex is functional on recipient cells both in vitro and in vivo. Indeed, treatment with sEVs from WT, but not KO cells rescued migratory defects observed either in CD98hc KO dermal fibroblasts or in keratinocytes in vitro. Furthermore, injection of sEVs at the margins of wound in impaired wound healing mouse models (epidermal CD98hc KO mice exhibiting healing defect and elderly mice) improved wound closure in vivo. CD98hc complex transferred from sEVs remained stabilized at least 7 days after injection. Thus, our findings reveal that in vivo treatment with sEVs containing integrin co-receptor CD98hc could improve multiple skin afflictions.
Collapse
Affiliation(s)
| | | | | | | | - Ayelet Levy
- INSERM U976, Hôpital St-Louis, Paris, France
| | | | - Chloé C Féral
- INSERM U1081, CNRS UMR7284, UCA, IRCAN, Nice, France.
| |
Collapse
|
|
24
|
Vipin CL, Kumar GSV. Exosome laden sprayable thermo-sensitive polysaccharide-based hydrogel for enhanced burn wound healing. Int J Biol Macromol 2025; 290:138712. [PMID: 39710019 DOI: 10.1016/j.ijbiomac.2024.138712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 11/26/2024] [Accepted: 12/10/2024] [Indexed: 12/24/2024]
Abstract
Severe burns pose significant threats to patient well-being, characterized by pain, inflammation, bacterial infection, and extended recovery periods. While exosome-loaded hydrogels have demonstrated considerable promise in wound healing, current formulations often fall short of achieving optimal therapeutic efficacy for burn wounds due to challenges related to their adaptability to wound shape and limited anti-bacterial capabilities. In this study a novel exosome laden sprayable thermosensitive polysaccharide-based hydrogel (ADA-aPF127@LL18/Exo) comprising alginate dialdehyde (ADA) and aminated Pluronic F127 (aPF127) was fabricated via Schiff base reaction. ADA-aPF127@LL18/Exo exhibited sustained release of exosome and enhanced antibacterial efficacy. Furthermore, the biological assessments displayed excellent biocompatibility and enhanced in vitro cell proliferation and migration. In a deep partial thickness burn model, ADA-aPF127@LL18/Exo significantly augmented wound healing processes by accelerating epithelialization, promoting granulation tissue formation and collagen deposition, inducing hair follicle regeneration, effectively mitigating inflammatory responses, and facilitating enhanced neovascularization. In conclusion, ADA-aPF127@LL18/Exo represents a highly promising therapeutic dressing for the treatment of deep burns, exhibiting multifaceted properties conducive to efficient wound management.
Collapse
Affiliation(s)
- C L Vipin
- Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology (BRIC-RGCB), Thycaud P.O, Poojappura, Thiruvananthapuram, Kerala 695014, India; Regional Centre for Biotechnology (BRIC-RCB), Faridabad, Haryana 121001, India
| | - G S Vinod Kumar
- Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology (BRIC-RGCB), Thycaud P.O, Poojappura, Thiruvananthapuram, Kerala 695014, India.
| |
Collapse
|
|
25
|
Razavi ZS, Aliniay Sharafshadehi S, Yousefi MH, Javaheri F, Rahimi Barghani MR, Afkhami H, Heidari F. Application of novel strategies in chronic wound management with focusing on pressure ulcers: new perspective. Arch Dermatol Res 2025; 317:320. [PMID: 39888392 DOI: 10.1007/s00403-024-03790-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 12/27/2024] [Accepted: 12/29/2024] [Indexed: 02/01/2025]
Abstract
Invading blood cells, extracellular tissue, and soluble mediators all play important roles in the wound-healing process. There is a substantial global burden of disease and mortality attributable to skin defects that do not heal. About 1% to 2% of the population in industrialized nations suffers from chronic wounds that don't heal, despite healthcare breakthroughs; this condition is very costly, costing about $25 billion each year in the US alone. Amputation, infection (affecting as many as 25% of chronic wounds), sepsis, and dermal replacements are all consequences of conventional therapeutic approaches like growth factor therapy and diabetic foot ulcers account for 85% of lower limb amputations. Despite these obstacles, scientists are constantly looking for new ways to speed healing and close wounds. The unique immunomodulatory capabilities and multipotency of mesenchymal stem cells (MSCs) have made them a potential therapeutic choice in tissue engineering and regenerative medicine. Animal models of wound healing have shown that MSCs can speed up the process by as much as 40% through enhancing angiogenesis, modulating inflammation, and promoting fibroblast migration. Clinical trials provide more evidence of their effectiveness; for instance, one RCT found that, after 12 weeks, patients treated with MSCs had a 72% smaller wound size than those in the control group. This review offers a thorough examination of MSCs by combining the latest research with preclinical evidence. Highlighting their potential to transform treatment paradigms, it delves into their biological properties, how they work during regeneration and healing, and therapeutic usefulness in controlling chronic wounds.
Collapse
Affiliation(s)
- Zahra Sadat Razavi
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Shahrzad Aliniay Sharafshadehi
- Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mohammad Hasan Yousefi
- Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Qom University of Medical Sciences, Qom, Iran
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Fatemeh Javaheri
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
| | | | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran.
| | - Fatemeh Heidari
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
- Department of Anatomy, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran.
| |
Collapse
|
|
26
|
Su D, Krongbaramee T, Swearson S, Sweat Y, Sweat M, Shao F, Eliason S, Amendt BA. Irx1 mechanisms for oral epithelial basal stem cell plasticity during reepithelialization after injury. JCI Insight 2025; 10:e179815. [PMID: 39782692 PMCID: PMC11721312 DOI: 10.1172/jci.insight.179815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 11/11/2024] [Indexed: 01/12/2025] Open
Abstract
The oral mucosa undergoes daily insults, and stem cells in the epithelial basal cell layer regenerate gingiva tissue to maintain oral health. The Iroquois Homeobox 1 (IRX1) protein is expressed in the stem cell niches in human/mouse oral epithelium and mesenchyme under homeostasis. We found that Irx1+/- heterozygous (Het) mice have delayed wound closure, delayed morphological changes of regenerated epithelium, and defective keratinocyte proliferation and differentiation during wound healing. RNA-Seq analyses between WT and Irx1+/- mice at 3 days postinjury (dpi) found impaired epithelial migration and decreased keratinocyte-related genes upon injury. IRX1-expressing cells are found in the gingival epithelial basal cell layer, a stem cell niche for gingival maintenance. IRX1-expressing cells are also found in cell niches in the underlying stroma. IRX1 activates SOX9 in the transient amplifying layer to increase cell proliferation, and EGF signaling is activated to induce cell migration. Krt14CreERT lineage tracing experiments reveal defects in the stratification of the Irx1+/- HET mouse oral epithelium. IRX1 is primed at the base of the gingiva in the basal cell layer of the oral epithelium, facilitating rapid and scarless wound healing through activating SOX9 and the EGF signaling pathway.
Collapse
Affiliation(s)
- Dan Su
- Department of Anatomy and Cell Biology
- Craniofacial Anomalies Research Center, Carver College of Medicine, and
| | - Tadkamol Krongbaramee
- Iowa Institute for Oral Health Research, College of Dentistry, The University of Iowa, Iowa City, Iowa, USA
- Division of Endodontics, Department of Restorative Dentistry & Periodontology, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Samuel Swearson
- Department of Anatomy and Cell Biology
- Craniofacial Anomalies Research Center, Carver College of Medicine, and
| | - Yan Sweat
- Harvard University, Boston, Massachusetts, USA
| | - Mason Sweat
- Harvard University, Boston, Massachusetts, USA
| | - Fan Shao
- Iowa Institute for Oral Health Research, College of Dentistry, The University of Iowa, Iowa City, Iowa, USA
| | - Steven Eliason
- Department of Anatomy and Cell Biology
- Craniofacial Anomalies Research Center, Carver College of Medicine, and
| | - Brad A. Amendt
- Department of Anatomy and Cell Biology
- Craniofacial Anomalies Research Center, Carver College of Medicine, and
- Iowa Institute for Oral Health Research, College of Dentistry, The University of Iowa, Iowa City, Iowa, USA
| |
Collapse
|
|
27
|
Song J, Wu Y, Chen Y, Sun X, Zhang Z. Epigenetic regulatory mechanism of macrophage polarization in diabetic wound healing (Review). Mol Med Rep 2025; 31:2. [PMID: 39422035 PMCID: PMC11551531 DOI: 10.3892/mmr.2024.13367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 09/24/2024] [Indexed: 10/19/2024] Open
Abstract
Diabetic wounds represent a significant complication of diabetes and present a substantial challenge to global public health. Macrophages are crucial effector cells that play a pivotal role in the pathogenesis of diabetic wounds, through their polarization into distinct functional phenotypes. The field of epigenetics has emerged as a rapidly advancing research area, as this phenomenon has the potential to markedly affect gene expression, cellular differentiation, tissue development and susceptibility to disease. Understanding epigenetic mechanisms is crucial to further exploring disease pathogenesis. A growing body of scientific evidence has highlighted the pivotal role of epigenetics in the regulation of macrophage phenotypes. Various epigenetic mechanisms, such as DNA methylation, histone modification and non‑coding RNAs, are involved in the modulation of macrophage phenotype differentiation in response to the various environmental stimuli present in diabetic wounds. The present review provided an overview of the various changes that take place in macrophage phenotypes and functions within diabetic wounds and discussed the emerging role of epigenetic modifications in terms of regulating macrophage plasticity in diabetic wounds. It is hoped that this synthesis of information will facilitate the elucidation of diabetic wound pathogenesis and the identification of potential therapeutic targets.
Collapse
Affiliation(s)
- Jielin Song
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
| | - Yuqing Wu
- The First Clinical Medical College, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510000, P.R. China
| | - Yunli Chen
- The First Clinical Medical College, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510000, P.R. China
| | - Xu Sun
- Department of Traditional Chinese Medicine Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
| | - Zhaohui Zhang
- Department of Traditional Chinese Medicine Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
| |
Collapse
|
|
28
|
Wang N, Ma F, Song H, He N, Zhang H, Li J, Liu Q, Xu C. Mesenchymal Stem Cell-Derived Extracellular Vesicles for Regenerative Applications and Radiotherapy. Cell Transplant 2025; 34:9636897241311019. [PMID: 39780320 PMCID: PMC11713979 DOI: 10.1177/09636897241311019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/12/2024] [Accepted: 12/15/2024] [Indexed: 01/11/2025] Open
Abstract
Tissue repair is an extremely crucial part of clinical treatment. During the course of disease treatment, surgery, chemotherapy, and radiotherapy cause tissue damage. On the other hand, Normal tissue from accidental or therapeutic exposure to high-dose radiation can cause severe tissue damage. There is an urgent need for developing medical countermeasures against radiation injury for tissue repair. Tissue repair involves the regeneration, proliferation, differentiation, and migration of tissue cells; imbalance of local tissue homeostasis, progressive chronic inflammation; decreased cell activity and stem cell function; and wound healing. Although many clinical treatments are currently available for tissue repair, they are expensive. The long recovery time and some unavoidable complications such as cell damage and the inflammatory reaction caused by radiotherapy have led to unsatisfactory results. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have similar tissue repair functions as MSCs. In tissue damage, EVs can be used as an alternative to stem cell therapy, thereby avoiding related complications such as immunological rejection. EVs play a major role in regulating tissue damage, anti-inflammation, pro-proliferation, and immune response, thus providing a diversified and efficient solution for the repair of disease- and radiotherapy-induced tissue damage. This article reviews the research progress of mesenchymal stem cell-derived EVs in promoting the repair of tissue including heart, lung, liver, intestine, skin, blood system, central nervous system, and tissue damage caused by radiotherapy, thereby aiming to offer new directions and ideas for the radiotherapy and regenerative applications.
Collapse
Affiliation(s)
- Ning Wang
- School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, China
| | - Feifei Ma
- School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, China
| | - Huijuan Song
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, State Key Laboratory of Advanced Medical Materials and Devices, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| | - Ningning He
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, State Key Laboratory of Advanced Medical Materials and Devices, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| | - Huanteng Zhang
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, State Key Laboratory of Advanced Medical Materials and Devices, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| | - Jianguo Li
- School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, China
| | - Qiang Liu
- School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, China
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, State Key Laboratory of Advanced Medical Materials and Devices, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| | - Chang Xu
- School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, China
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, State Key Laboratory of Advanced Medical Materials and Devices, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| |
Collapse
|
|
29
|
Wolski M, Ciesielski T, Buczma K, Fus Ł, Girstun A, Trzcińska-Danielewicz J, Cudnoch-Jędrzejewska A. Administration of Adipose-Derived Stem Cells After the Onset of the Disease Does Not Lower the Levels of Inflammatory Cytokines IL1 and IL6 in a Rat Model of Necrotizing Enterocolitis. Biomedicines 2024; 12:2897. [PMID: 39767803 PMCID: PMC11727438 DOI: 10.3390/biomedicines12122897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/15/2024] [Accepted: 12/16/2024] [Indexed: 01/16/2025] Open
Abstract
Background/Objectives: Research on the roles of stem cells in necrotizing enterocolitis (NEC) has primarily focused on the effects of bone marrow- and amniotic fluid-derived stem cells in mitigating the clinical manifestations of the disease. However, the potential of adipose tissue-derived stem cells (ADSCs) remains unexplored in this context. The aim of this study was to evaluate the therapeutic potential of ADSC administration during the active inflammatory phase of NEC, with a specific focus on reducing the levels of the inflammatory cytokines IL-1 and IL-6. Methods: A self-modified hypoxia-hypothermia-formula feeding rat NEC model was employed. A total of 117 rat pups were divided into two groups: a treatment group (NEC-ADSC, n = 55) and a control group (NEC-PLCB (placebo), n = 62). In the NEC-ADSC group, ADSCs were administered intraperitoneally 24 h into the NEC protocol. After 72 h, bowel and fluid samples were collected for analysis. Results: The analysis revealed no significant effect on NEC histopathology (p = 0.347) or on the levels of IL-1 and IL-6 (p = 0.119 and p = 0.414, respectively). Conclusions: The administration of adipose tissue-derived stem cells after the onset of necrotizing enterocolitis does not reduce the levels of inflammatory cytokines IL-1 and IL-6, nor does it influence the histopathological outcomes of the disease in the rat model. Further research is needed to explore the potential therapeutic role of adipose tissue-derived stem cells in the treatment of necrotizing enterocolitis.
Collapse
Affiliation(s)
- Marek Wolski
- Department of Pediatric Surgery, Medical University of Warsaw, Zwirki i Wigury 63a, 02-091 Warsaw, Poland
| | - Tomasz Ciesielski
- Laboratory of Centre for Preclinical Research, Chair and Department of Experimental and Clinical Physiology, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland; (T.C.); (K.B.); (A.C.-J.)
| | - Kasper Buczma
- Laboratory of Centre for Preclinical Research, Chair and Department of Experimental and Clinical Physiology, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland; (T.C.); (K.B.); (A.C.-J.)
| | - Łukasz Fus
- Department of Pathology, Medical University of Warsaw, Pawinskiego 7, 02-106 Warsaw, Poland;
| | - Agnieszka Girstun
- Department of Molecular Biology, Institute of Biochemistry, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (A.G.); (J.T.-D.)
| | - Joanna Trzcińska-Danielewicz
- Department of Molecular Biology, Institute of Biochemistry, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (A.G.); (J.T.-D.)
| | - Agnieszka Cudnoch-Jędrzejewska
- Laboratory of Centre for Preclinical Research, Chair and Department of Experimental and Clinical Physiology, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland; (T.C.); (K.B.); (A.C.-J.)
| |
Collapse
|
|
30
|
Lu J, Zhang W, Zhu Y, Luo P, Tong X, Xie S, Jiang L, Guo X, Huang J, Gu M, Ding X, Xian S, Huang R, Ji S, Xia Z. Revealing the Therapeutic Potential of Stem Cells in Burn Healing: A Deeper Understanding of the Therapeutic Mechanisms of Epidermal Stem Cells and Mesenchymal Stem Cells. Stem Cells Int 2024; 2024:1914585. [PMID: 39717868 PMCID: PMC11666318 DOI: 10.1155/2024/1914585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 07/20/2024] [Accepted: 08/19/2024] [Indexed: 12/25/2024] Open
Abstract
Background: Burns are a global public health issue and a major cause of disability and death around the world. Stem cells, which are the undifferentiated cells with the potential for indefinite proliferation and multilineage differentiation, have the ability to replace injured skin and facilitate the wound repair process through paracrine mechanisms. In light of this, the present study aims to conduct a bibliometric analysis in order to identify research hotspots of stem cell-related burns and assess global research tendencies. Methods: To achieve this objective, we retrieved scientific publications on burns associated with stem cells covering the period from January 1, 1978, to October 13, 2022, from the Web of Science Core Collection (WoSCC). Bibliometric analyses, including production and collaboration analyses between countries, institutions, authors, and journals, as well as keyword and topic analyses, were conducted using the bibliometrix R package, CiteSpace, and VOSviewer. Results: A total of 1648 burns associated with stem cell documents were published and listed on WOSCC. The most contributive country, institution, journal, and author were the United States, LV Prasad Eye Institute, Burns, and Scheffer C.G. Tseng, respectively. More importantly, combined with historical direct citation network, trend topic analysis, keyword co-occurrence network, and substantial literature analysis, we eventually summarized the research hotspots and frontiers on burns associated stem cell reasearch. Conclusion: The present study obtained deep insight into the developing trends and research hotspots on burns associated with stem cells, which arouses growing concerns and implies increasing clinical implications. The mechanism and therapeutics of epidermal stem cells (ESCs) for burn wounds and the mechanism of mesenchymal stem cells (MSCs) and MSC-derived exosomes for burns wounds are two research hotspots in this field.
Collapse
Affiliation(s)
- Jianyu Lu
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Wei Zhang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Yushu Zhu
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Pengfei Luo
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Xirui Tong
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Sujie Xie
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Luofeng Jiang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Xinya Guo
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Jie Huang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Minyi Gu
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Xinran Ding
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Shuyuan Xian
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Runzhi Huang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Shizhao Ji
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Zhaofan Xia
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| |
Collapse
|
|
31
|
Xiang H, Ding P, Qian J, Lu E, Sun Y, Lee S, Zhao Z, Sun Z, Zhao Z. Exosomes derived from minor salivary gland mesenchymal stem cells: a promising novel exosome exhibiting pro-angiogenic and wound healing effects similar to those of adipose-derived stem cell exosomes. Stem Cell Res Ther 2024; 15:462. [PMID: 39627883 PMCID: PMC11616330 DOI: 10.1186/s13287-024-04069-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 11/20/2024] [Indexed: 12/06/2024] Open
Abstract
BACKGROUNDS Minor salivary gland mesenchymal stem cells (MSGMSCs) can be easily extracted and have a broad range of sources. Applying exosomes to wounds is a highly promising method for promoting wound healing. Exosomes derived from different stem cell types have been proven to enhance wound healing, with adipose-derived stem cell (ADSC)-derived exosomes being the most extensively researched. Considering that MSGMSCs have advantages such as easier extraction compared to ADSCs, MSGMSCs should also be a very promising type of stem cell in exosome therapy. However, whether MSGMSC-derived exosomes (MSGMSC-exos) can promote wound healing and how they compare to ADSC-derived exosomes (ADSC-exos) in the wound healing process remain unclear. MATERIALS The effects of MSGMSC-exos and ADSC-exos on angiogenesis in wound healing were investigated in vitro using CCK-8, scratch assays, and tube formation assays. Subsequently, the promotion of wound healing by MSGMSC-exos and ADSC-exos was evaluated in vivo using a full-thickness wound defect model in mice. Immunohistochemistry was used to verify the effects of MSGMSC-exos and ADSC-exos on promoting collagen deposition, angiogenesis, and cell proliferation in the wound. Immunofluorescence staining was performed to investigate the role of MSGMSC-exos and ADSC-exos in modulating the inflammatory response in the wound. Furthermore, proteomic sequencing was conducted to investigate the functional similarities and differences between the proteomes of MSGMSC-exos and ADSC-exos, with key protein contents verified by ELISA. RESULTS MSGMSC-exos exhibited similar effects as ADSC-exos in promoting the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, with a comparable dose-dependent effect. In vivo experiments confirmed that MSGMSC-exos have similar wound healing-promoting functions as ADSC-exos. MSGMSC-exos promoted the neovascularization and maturation of blood vessels in vivo at a level comparable to ADSC-exos. Despite MSGMSC-exos showing less collagen deposition than ADSC-exos, they exhibited stronger anti-scar formation and anti-inflammatory effects. Proteomic analysis revealed that the proteins promoting wound healing in both MSGMSC-exos and ADSC-exos were relatively conserved, with ITGB1 identified as a critical protein for angiogenesis. Further differential analysis revealed that the functions specifically enriched in MSGMSC-exos and ADSC-exos reflected the functions of their source tissue. CONCLUSIONS Our study confirms that MSGMSC-exos exhibit highly similar wound healing and angiogenesis-promoting functions compared to ADSC-exos, and the proteins involved in promoting wound healing in both are relatively conserved. Moreover, MSGMSC-exos show stronger anti-scar formation and anti-inflammatory effects than ADSC-exos. This suggests that MSGMSCs are a promising stem cell source with broad applications in wound healing treatment.
Collapse
Affiliation(s)
- Haibo Xiang
- Department of Plastic Surgery, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Pengbing Ding
- Department of Plastic Surgery, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Jiaying Qian
- Department of Plastic Surgery, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Enhang Lu
- Department of Plastic Surgery, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Yimou Sun
- Department of Plastic Surgery, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Seyeon Lee
- Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Zhenkun Zhao
- Department of Plastic Surgery, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Zhixuan Sun
- Department of Plastic Surgery, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Zhenmin Zhao
- Department of Plastic Surgery, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China.
| |
Collapse
|
|
32
|
Thakur A, Rai D. Global requirements for manufacturing and validation of clinical grade extracellular vesicles. THE JOURNAL OF LIQUID BIOPSY 2024; 6:100278. [PMID: 40027307 PMCID: PMC11863704 DOI: 10.1016/j.jlb.2024.100278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/17/2024] [Accepted: 11/18/2024] [Indexed: 03/05/2025]
Abstract
Extracellular vesicles (EVs) are nanovesicles released from different cell types from biofluids such as blood, urine, and cerebrospinal fluid. They vary in size and biomarkers, and their biogenesis pathways allow them to be divided into three major types: exosomes, micro-vesicles, and apoptotic bodies. EVs have been studied in the context of diagnosis and therapeutic intervention of various pathological conditions such as cancer, neurodegenerative diseases, and pulmonary diseases. However, the production of EV-based therapeutics can be affected by the source, heterogeneity, or disease, raising questions about the manufacturing and validation of EVs of clinical grade and their scope regarding good manufacturing practice (GMP) in the industry. To address this, we have discussed the state-of-the-art requirements for EV production that must occur in a GMP-compliant environment with a reliable and traceable source. Additionally, EVs' homogeneity and the therapeutics' purity and stability must be analyzed and validated. Quality control measures must also be established to ensure the safety and efficacy of EVs. In conclusion, these considerations must be weighed carefully when manufacturing and validating EVs of clinical grade to ensure their safety and efficacy for therapeutic use.
Collapse
Affiliation(s)
- Abhimanyu Thakur
- Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Deepika Rai
- Smidt Heart Institute, Cedars-Sinai Medical Centre, Los Angeles, CA, United States
| |
Collapse
|
|
33
|
Ziadlou R, Pandian GN, Hafner J, Akdis CA, Stingl G, Maverakis E, Brüggen M. Subcutaneous adipose tissue: Implications in dermatological diseases and beyond. Allergy 2024; 79:3310-3325. [PMID: 39206504 PMCID: PMC11657049 DOI: 10.1111/all.16295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 07/19/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024]
Abstract
Subcutaneous adipose tissue (SAT) is the deepest component of the three-layered cutaneous integument. While mesenteric adipose tissue-based immune processes have gained recognition in the context of the metabolic syndrome, SAT has been traditionally considered primarily for energy storage, with less attention to its immune functions. SAT harbors a reservoir of immune and stromal cells that significantly impact metabolic and immunologic processes not only in the skin, but even on a systemic level. These processes include wound healing, cutaneous and systemic infections, immunometabolic, and autoimmune diseases, inflammatory skin diseases, as well as neoplastic conditions. A better understanding of SAT immune functions in different processes, could open avenues for novel therapeutic interventions. Targeting SAT may not only address SAT-specific diseases but also offer potential treatments for cutaneous or even systemic conditions. This review aims to provide a comprehensive overview on SAT's structure and functions, highlight recent advancements in understanding its role in both homeostatic and pathological conditions within and beyond the skin, and discuss the main questions for future research in the field.
Collapse
Affiliation(s)
- Reihane Ziadlou
- Faculty of MedicineUniversity of ZurichZurichSwitzerland
- Department of DermatologyUniversity Hospital ZurichZurichSwitzerland
- Christine Kühne Center for Allergy Research and Education CK‐CAREDavosSwitzerland
- Swiss Institute of Allergy and Asthma Research (SIAF)University of ZurichZurichSwitzerland
| | - Ganesh N. Pandian
- Institute for Integrated Cell‐Material Science (WPI‐iCeMS)Kyoto UniversityKyotoJapan
| | - Jürg Hafner
- Faculty of MedicineUniversity of ZurichZurichSwitzerland
- Department of DermatologyUniversity Hospital ZurichZurichSwitzerland
| | - Cezmi A. Akdis
- Faculty of MedicineUniversity of ZurichZurichSwitzerland
- Christine Kühne Center for Allergy Research and Education CK‐CAREDavosSwitzerland
- Swiss Institute of Allergy and Asthma Research (SIAF)University of ZurichZurichSwitzerland
| | - Georg Stingl
- Department of DermatologyMedical University of ViennaViennaAustria
| | | | - Marie‐Charlotte Brüggen
- Faculty of MedicineUniversity of ZurichZurichSwitzerland
- Department of DermatologyUniversity Hospital ZurichZurichSwitzerland
- Christine Kühne Center for Allergy Research and Education CK‐CAREDavosSwitzerland
| |
Collapse
|
|
34
|
Sharma Y, Ghatak S, Sen CK, Mohanty S. Emerging technologies in regenerative medicine: The future of wound care and therapy. J Mol Med (Berl) 2024; 102:1425-1450. [PMID: 39358606 DOI: 10.1007/s00109-024-02493-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 09/10/2024] [Accepted: 09/23/2024] [Indexed: 10/04/2024]
Abstract
Wound healing, an intricate biological process, comprises orderly phases of simple biological processed including hemostasis, inflammation, angiogenesis, cell proliferation, and ECM remodeling. The regulation of the shift in these phases can be influenced by systemic or environmental conditions. Any untimely transitions between these phases can lead to chronic wounds and scarring, imposing a significant socio-economic burden on patients. Current treatment modalities are largely supportive in nature and primarily involve the prevention of infection and controlling inflammation. This often results in delayed healing and wound complications. Recent strides in regenerative medicine and tissue engineering offer innovative and patient-specific solutions. Mesenchymal stem cells (MSCs) and their secretome have gained specific prominence in this regard. Additionally, technologies like tissue nano-transfection enable in situ gene editing, a need-specific approach without the requirement of complex laboratory procedures. Innovating approaches like 3D bioprinting and ECM bioscaffolds also hold the potential to address wounds at the molecular and cellular levels. These regenerative approaches target common healing obstacles, such as hyper-inflammation thereby promoting self-recovery through crucial signaling pathway stimulation. The rationale of this review is to examine the benefits and limitations of both current and emerging technologies in wound care and to offer insights into potential advancements in the field. The shift towards such patient-centric therapies reflects a paradigmatic change in wound care strategies.
Collapse
Affiliation(s)
- Yashvi Sharma
- Stem Cell Facility (DBT-Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India
| | - Subhadip Ghatak
- Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
- McGowan Institute of Regenerative Medicine, Department of Surgery, University of Pittsburgh, 419 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA, 15219, USA
| | - Chandan K Sen
- Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
- McGowan Institute of Regenerative Medicine, Department of Surgery, University of Pittsburgh, 419 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA, 15219, USA.
| | - Sujata Mohanty
- Stem Cell Facility (DBT-Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India.
| |
Collapse
|
|
35
|
Sankaranarayanan J, Lee SC, Kim HK, Kang JY, Kuppa SS, Seon JK. Exosomes Reshape the Osteoarthritic Defect: Emerging Potential in Regenerative Medicine-A Review. Int J Stem Cells 2024; 17:381-396. [PMID: 38246659 PMCID: PMC11612219 DOI: 10.15283/ijsc23108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 10/05/2023] [Accepted: 11/28/2023] [Indexed: 01/23/2024] Open
Abstract
Osteoarthritis (OA) is a joint disorder caused by wear and tear of the cartilage that cushions the joints. It is a progressive condition that can cause significant pain and disability. Currently, there is no cure for OA, though there are treatments available to manage symptoms and slow the progression of the disease. A chondral defect is a common and devastating lesion that is challenging to treat due to its avascular and aneural nature. However, there are conventional therapies available, ranging from microfracture to cell-based therapy. Anyhow, its efficiency in cartilage defects is limited due to unclear cell viability. Exosomes have emerged as a potent therapeutic tool for chondral defects because they are a complicated complex containing cargo of proteins, DNA, and RNA as well as the ability to target cells due to their phospholipidic composition and the altering exosomal contents that boost regeneration potential. Exosomes are used in a variety of applications, including tissue healing and anti-inflammatory therapy. As in recent years, biomaterials-based bio fabrication has gained popularity among the many printable polymer-based hydrogels, tissue-specific decellularized extracellular matrix might boost the effects rather than an extracellular matrix imitating environment, a short note has been discussed. Exosomes are believed to be the greatest alternative option for current cell-based therapy, and future progress in exosome-based therapy could have a greater influence in the field of orthopaedics. The review focuses extensively on the insights of exosome use and scientific breakthroughs centered OA.
Collapse
Affiliation(s)
- Jaishree Sankaranarayanan
- Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun, Korea
- Department of Orthopaedic Surgery, Center for Joint Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea
- Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, Gwangju, Korea
| | - Seok Cheol Lee
- Department of Orthopaedic Surgery, Center for Joint Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea
- Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, Gwangju, Korea
| | - Hyung Keun Kim
- Department of Orthopaedic Surgery, Center for Joint Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea
- Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, Gwangju, Korea
| | - Ju Yeon Kang
- Department of Orthopaedic Surgery, Center for Joint Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea
- Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, Gwangju, Korea
| | - Sree Samanvitha Kuppa
- Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun, Korea
- Department of Orthopaedic Surgery, Center for Joint Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea
- Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, Gwangju, Korea
| | - Jong Keun Seon
- Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun, Korea
- Department of Orthopaedic Surgery, Center for Joint Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea
- Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, Gwangju, Korea
| |
Collapse
|
|
36
|
Li Y, Wang Y, Zhao H, Pan Q, Chen G. Engineering Strategies of Plant-Derived Exosome-Like Nanovesicles: Current Knowledge and Future Perspectives. Int J Nanomedicine 2024; 19:12793-12815. [PMID: 39640047 PMCID: PMC11618857 DOI: 10.2147/ijn.s496664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 11/23/2024] [Indexed: 12/07/2024] Open
Abstract
Plant-derived exosome-like nanovesicles (PELNs) from edible plants, isolated by ultracentrifugation, size exclusion chromatography or other methods, were proved to contain a variety of biologically active and therapeutically specific components. Recently, investigations in the field of PELN-based biomedicine have been conducted, which positioned those nanovesicles as promising tools for prevention and treatment of several diseases, with their natural origin potentially offering superior biocompatibility and bioavailability. However, the inadequate targeting and limited therapeutic effects constrain the utility and clinical translation of PELNs. Thus, strategies aiming at bridging the gap by engineering natural PELNs have been of great interest. Those approaches include membrane hybridization, physical and chemical surface functionalization and encapsulation of therapeutic payloads. Herein, we provide a comprehensive overview of the biogenesis and composition, isolation and purification methods and characterization of PELNs, as well as their therapeutic functions. Current knowledge on the construction strategies and biomedical application of engineered PELNs were reviewed. Additionally, future directions and perspectives in this field were discussed in order to further enrich and expand the prospects for the application of engineered PELNs.
Collapse
Affiliation(s)
- Yuhan Li
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Yulong Wang
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Hongrui Zhao
- Intensive Care Medicine Department, Yuhuangding Hospital, Yantai, People’s Republic of China
| | - Qi Pan
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Guihao Chen
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| |
Collapse
|
|
37
|
Sun X, Ding H, Li X, Wu Y, Huang X. Disulfiram-loaded nanovesicles hydrogel promotes healing of diabetic wound. J Transl Med 2024; 22:1066. [PMID: 39593097 PMCID: PMC11600750 DOI: 10.1186/s12967-024-05875-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Traditional methods for treating diabetic wounds are limited in effectiveness because of their long healing times, the risk of immune rejection, and susceptibility to infection. Suppressing neutrophil extracellular traps (NETs) is an effective strategy for reducing persistent inflammation in diabetic wounds. Although disulfiram (DSF) can inhibit the significant increase of NETs in diabetic wounds, oral DSF suffers from rapid and harmful metabolism in the liver. To address these challenges, we developed a nanomedicine formulation in which DSF was incorporated into the hydrogel. METHODS In this study, we developed a DSF-laden sodium alginate hydrogel wound dressing, DEP@SA, and characterized its composition, properties, and performance. We examined the effects of DEP@SA on inflammatory phase-related markers such as NETs and their pathway proteins, inflammatory factors, and macrophage phenotypes in a high-glucose environment in vivo and in vitro. In addition, the effects of DEP@SA on tissue regenerative capacity such as epidermal proliferative migration and angiogenesis, were also assessed. RESULTS The results showed that by utilizing extracellular vesicles as a drug delivery system, we effectively mitigated the degradation of DSF via direct contact with aqueous solutions and ensured the stability of DSF@SA, which could then be applied to diabetic wounds. The inflammatory phase-related indicators revealed that DSF@SA effectively reduced inflammation levels, decreased NETs formation, suppressed the Caspase-1/GSDMD pathway in neutrophils, and promoted the polarization of M2 macrophages. Moreover, the hydrogel accelerated wound healing by promoting angiogenesis and re-epithelialization, thereby shortening the diabetic wound healing time. CONCLUSIONS This study confirmed that the DSF@SA composite dressing has the potential to enhance diabetic wound repair and offers a novel approach for drug reutilization.
Collapse
Affiliation(s)
- Xingzi Sun
- Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China
| | - Hanxi Ding
- Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China
| | - Xingyu Li
- Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China
| | - Yongjian Wu
- Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China.
| | - Xi Huang
- Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China.
| |
Collapse
|
|
38
|
Ding K, Kong J, Li L, Selaru FM, Parian A, Mao HQ. Current and emerging therapeutic strategies for perianal fistula in Crohn's disease patients. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2024; 101:159-182. [PMID: 39521599 PMCID: PMC11753511 DOI: 10.1016/bs.apha.2024.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
The long-term remission rates achieved with current treatment options for Crohn's disease with perianal fistula (CD-PAF)-including antibiotics, biologics, immunomodulators, and Janus kinase inhibitors, often combined with advanced surgical interventions-remain unsatisfactory. This chapter explores several innovative biomaterials-based solutions, such as plugs, adhesives, fillers, and stem cell-based therapies. The key approaches and treatment outcomes of these advanced therapies are examined, focusing on their ability to modulate the immune response, promote tissue healing, and improve patient outcomes. Additionally, the chapter discusses future directions, including the optimization of biomaterial designs, enhancement of delivery and retention of regenerative therapies, and a deeper understanding of the underlying mechanisms of healing.
Collapse
Affiliation(s)
- Kailei Ding
- Institute for NanoBioTechnology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Materials Science and Engineering, Whiting School of Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Jiayuan Kong
- Institute for NanoBioTechnology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Materials Science and Engineering, Whiting School of Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Ling Li
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Florin M Selaru
- Institute for NanoBioTechnology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Alyssa Parian
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
| | - Hai-Quan Mao
- Institute for NanoBioTechnology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Materials Science and Engineering, Whiting School of Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
| |
Collapse
|
|
39
|
Selvadoss A, Baby HM, Zhang H, Bajpayee AG. Harnessing exosomes for advanced osteoarthritis therapy. NANOSCALE 2024; 16:19174-19191. [PMID: 39323205 PMCID: PMC11799831 DOI: 10.1039/d4nr02792b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 09/15/2024] [Indexed: 09/27/2024]
Abstract
Exosomes are nanosized, lipid membrane vesicles secreted by cells, facilitating intercellular communication by transferring cargo from parent to recipient cells. This capability enables biological crosstalk across multiple tissues and cells. Extensive research has been conducted on their role in the pathogenesis of degenerative musculoskeletal diseases such as osteoarthritis (OA), a chronic and painful joint disease that particularly affects cartilage. Currently, no effective treatment exists for OA. Given that exosomes naturally modulate synovial joint inflammation and facilitate cartilage matrix synthesis, they are promising candidates as next generation nanocarriers for OA therapy. Recent advancements have focused on engineering exosomes through endogenous and exogenous approaches to enhance their joint retention, cartilage and chondrocyte targeting properties, and therapeutic content enrichment, further increasing their potential for OA drug delivery. Notably, charge-reversed exosomes that utilize electrostatic binding interactions with cartilage anionic aggrecan glycosaminoglycans have demonstrated the ability to penetrate the full thickness of early-stage arthritic cartilage tissue following intra-articular administration, maximizing their therapeutic potential. These exosomes offer a non-viral, naturally derived, cell-free carrier for OA drug and gene delivery applications. Efforts to standardize exosome harvest, engineering, and property characterization methods, along with scaling up production, will facilitate more efficient and rapid clinical translation. This article reviews the current state-of-the-art, explores opportunities for exosomes as OA therapeutics, and identifies potential challenges in their clinical translation.
Collapse
Affiliation(s)
- Andrew Selvadoss
- Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA.
| | - Helna M Baby
- Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
| | - Hengli Zhang
- Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
| | - Ambika G Bajpayee
- Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA.
- Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
| |
Collapse
|
|
40
|
Wolski M, Ciesielski T, Buczma K, Fus Ł, Girstun A, Trzcińska-Danielewicz J, Cudnoch-Jędrzejewska A. Administration of Adipose Tissue Derived Stem Cells before the Onset of the Disease Lowers the Levels of Inflammatory Cytokines IL-1 and IL-6 in the Rat Model of Necrotizing Enterocolitis. Int J Mol Sci 2024; 25:11052. [PMID: 39456833 PMCID: PMC11507542 DOI: 10.3390/ijms252011052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 10/10/2024] [Accepted: 10/11/2024] [Indexed: 10/28/2024] Open
Abstract
There is little research concerning the role of stem cells in necrotizing enterocolitis (NEC). Bone marrow-derived mesenchymal stem cells (BMDSC) and amniotic fluid-derived stem cells significantly reduced the amount and severity of NEC in the animal models. ADSCs share similar surface markers and differentiation potential with BMDSCs. Their potential role in the setting of NEC has not been researched before. The hypothesis of the study was that prophylactic intraperitoneal administration of ADSCs before the onset of the disease will result in limiting the inflammatory response, effecting a lower incidence of NEC. On a molecular level, this should result in lowering the levels of inflammatory cytokines IL-1 and IL-6. The local ethical committee for animal experiments approval was acquired (WAW2/093/2021). We utilized a self-modified rat NEC model based on single exposure to hypothermia, hypoxia, and formula feeding. One hundred and twenty-eight rat puppies were divided into two groups-prophylaxis (ADSC-NEC, n = 66) and control group (NEC-PLCB, n = 62)-to measure the influence of ADSCs administration on the inflammatory changes in NEC, the level of cell engraftment, and the histopathology of the disease. The analysis did not show a significant effect on histopathology between groups, H(2) = 2.12; p = 0.347; η²H = 0.00. The intensity of the NEC variable results was similar across the analyzed groups (NEC-PLCB and ADSC-NEC). For IL-1 and IL-6, the difference between the NEC-PLCB group and the ADSC-NEC group was statistically significant, p = 0.002 and p < 0.001, respectively. To conclude, administration of adipose tissue-derived stem cells before the onset of the disease lowers the levels of inflammatory cytokines IL-1 and IL-6 but does not affect the histopathological results in the rat model of NEC.
Collapse
Affiliation(s)
- Marek Wolski
- Department of Pediatric Surgery, Medical University of Warsaw, Zwirki i Wigury 63a, 02-091 Warsaw, Poland
| | - Tomasz Ciesielski
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland; (T.C.); (K.B.); (A.C.-J.)
| | - Kasper Buczma
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland; (T.C.); (K.B.); (A.C.-J.)
| | - Łukasz Fus
- Department of Pathology, Medical University of Warsaw, Pawinskiego 7, 02-106 Warsaw, Poland;
| | - Agnieszka Girstun
- Department of Molecular Biology, Institute of Biochemistry, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (A.G.); (J.T.-D.)
| | - Joanna Trzcińska-Danielewicz
- Department of Molecular Biology, Institute of Biochemistry, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (A.G.); (J.T.-D.)
| | - Agnieszka Cudnoch-Jędrzejewska
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland; (T.C.); (K.B.); (A.C.-J.)
| |
Collapse
|
|
41
|
Tang S, Cai P, He H, Tian Y, Hao R, Liu X, Jing T, Xu Y, Li X. Global trends in the clinical utilization of exosomes in dermatology: a bibliometric analysis. Front Med (Lausanne) 2024; 11:1462085. [PMID: 39450105 PMCID: PMC11500466 DOI: 10.3389/fmed.2024.1462085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 09/11/2024] [Indexed: 10/26/2024] Open
Abstract
The arena of exosomal research presents substantial emerging prospects for clinical dermatology applications. This investigation conducts a thorough analysis of the contemporary global research landscape regarding exosomes and their implications for dermatological applications over the preceding decade. Employing bibliometric methodologies, this study meticulously dissects the knowledge framework and identifies dynamic trends within this specialized field. Contemporary scholarly literature spanning the last decade was sourced from the Web of Science Core Collection (WoSCC) database. Subsequent to retrieval, both quantitative and visual analyses of the pertinent publications were performed utilizing the analytical software tools VOSviewer and Citespace. A comprehensive retrieval yielded 545 scholarly articles dated from January 1, 2014, to December 31, 2023. Leading the research forefront are institutions such as Shanghai Jiao Tong University, The Fourth Military Medical University, and Sun Yat-sen University. The most prolific contributors on a national scale are China, the United States, and South Korea. Among the authors, Zhang Bin, Zhang Wei, and Zhang Yan emerge as the most published, with Zhang Bin also achieving the distinction of being the most cited. The International Journal of Molecular Sciences leads in article publications, whereas Stem Cell Research & Therapy holds the pinnacle in citation rankings. Theranostics boasts the highest impact factor among the periodicals. Current research hotspots in this area include Adipose mesenchymal stem cell-derived exosomes(ADSC-Exos), diabetic skin wounds, cutaneous angiogenesis, and the combination of biomaterials and exosomes. This manuscript constitutes the inaugural comprehensive bibliometric analysis that delineates the prevailing research trends and advancements in the clinical application of exosomes in dermatology. These analyses illuminate the contemporary research focal points and trajectories, providing invaluable insights that will inform further exploration within this domain.
Collapse
Affiliation(s)
- Shiqin Tang
- School of Clinical Medicine, Hebei University of Engineering, Handan, Hebei, China
| | - Pai Cai
- School of Information Engineering, Suihua University, Suihua, Heilongjiang, China
| | - Huina He
- School of Clinical Medicine, Hebei University of Engineering, Handan, Hebei, China
| | - Yanan Tian
- School of Clinical Medicine, Hebei University of Engineering, Handan, Hebei, China
| | - Ruiying Hao
- Affiliated Hospital of Hebei University of Engineering, Handan, Hebei, China
| | - Xin Liu
- Handan Stomatological Hospital, Endodontics, Handan, Hebei, China
| | - Tingting Jing
- Affiliated Hospital of Hebei University of Engineering, Handan, Hebei, China
- Hebei Key Laboratory of Immunological Dermatology, Handan, Hebei, China
| | - Yanyan Xu
- Affiliated Hospital of Hebei University of Engineering, Handan, Hebei, China
- Hebei Key Laboratory of Immunological Dermatology, Handan, Hebei, China
| | - Xiaojing Li
- School of Clinical Medicine, Hebei University of Engineering, Handan, Hebei, China
- Affiliated Hospital of Hebei University of Engineering, Handan, Hebei, China
- Hebei Key Laboratory of Immunological Dermatology, Handan, Hebei, China
| |
Collapse
|
|
42
|
Bozkurt AS, Yılmaz ŞG, Kaplan DS, Bal R. The regenerative effect of exosomes isolated from mouse embryonic fibroblasts in mice created as a sciatic nerve crush injury model. Mol Biol Rep 2024; 51:1046. [PMID: 39388029 DOI: 10.1007/s11033-024-09962-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 09/20/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND Exosomes (Exos) are candidates for functional recovery and regeneration following sciatic nerve crushed (SNC) injury due to their composition which can accelerate tissue regeneration. Therefore, mouse embryonic fibroblast-derived exosomes were evaluated for their regenerative capacity in SNC injury. METHODS AND RESULTS In the study, 40 Balb/c males (20 ± 5 g) and two pregnant mice (for embryonic fibroblast tissue) were used and crushed injury was induced in the left sciatic nerve with an aneurysm clamp. Sciatic nerve model mice were randomly divided into 5 groups (n = 8; control, n = 8; sham, n = 8; SNC, n = 8; Mouse embryonic fibroblast exosome (mExo), n = 8; SNC + Mouse embryonic fibroblast exosome (SNC + mExo). Rotarod tests for motor functions and hot plate and von Frey tests for sensory functions were analyzed in the groups. Expression changes of exosome genes (RARRES1, NAGS, HOXA13, and MEIS1) immunohistochemical analysis of these gene proteins, and structural exosome NF-200 and S100 proteins were evaluated by confocal microscopy. Behavioral analyses showed that the damage in SNC was significant between groups on day14 and day28 (P < 0.05). In behavioral analyses, it was determined that motor functions and mechanical sensitivity lost in SNC were regained after mExo treatment. While expression of all genes was detected in MEF-derived exosomes, the high expression was MESI1 and the low expression was HOXA13. NF200, an indicator of axon number and neurofilament density, was found to decrease in SNC (P < 0.001) and increase after treatment, but not significantly. The decreased S100 protein levels in SNC and the increase detected after treatment were not significant. CONCLUSION The expression of four mRNAs in mExos indicates that these genes may have an effect on regenerative processes after SNC injury. The regenerative process supported by tissue protein expressions demonstrates the therapeutic potential of mExo treatment.
Collapse
Affiliation(s)
- Ahmet Sarper Bozkurt
- Physiology Department, Medicine Faculty, Gaziantep University, Gaziantep, Turkey.
| | - Şenay Görücü Yılmaz
- Nutrition and Dietetics Department, Health Science Faculty, Gaziantep University, Gaziantep, Turkey
| | - Davut Sinan Kaplan
- Physiology Department, Medicine Faculty, Gaziantep University, Gaziantep, Turkey
| | - Ramazan Bal
- Physiology Department, Medicine Faculty, Gaziantep University, Gaziantep, Turkey
| |
Collapse
|
|
43
|
Manzoor T, Farooq N, Sharma A, Shiekh PA, Hassan A, Dar LA, Nazir J, Godha M, Sheikh FA, Gugjoo MB, Saleem S, Ahmad SM. Exosomes in nanomedicine: a promising cell-free therapeutic intervention in burn wounds. Stem Cell Res Ther 2024; 15:355. [PMID: 39385310 PMCID: PMC11462792 DOI: 10.1186/s13287-024-03970-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 10/01/2024] [Indexed: 10/12/2024] Open
Abstract
Burn injuries are serious injuries that have a big impact on a person's health and can even cause death. Incurring severe burns can incite an immune response and inflammation within the body, alongside metabolic changes. It is of utmost importance to grasp the fact that the effects of the burn injury extend beyond the body, affecting the mind and overall well-being. Burn injuries cause long-lasting changes that need to be taken care of in order to improve their quality of life. The intricate process of skin regeneration at the site of a burn wound involves a complex and dynamic interplay among diverse cells, growth factors, nerves, and blood vessels. Exciting opportunities have arisen in the field of stem cells and regenerative medicine, allowing us to explore the development of cell-free-based alternatives that can aid in the treatment of burn injuries. These cell-free-based therapies have emerged as a promising facet within regenerative medicine. Exosomes, also referred to as naturally occurring nanoparticles, are small endosome-derived vesicles that facilitate the delivery of molecular cargo between the cells, thus allowing intercellular communication. The knowledge gained in this field has continued to support their therapeutic potential, particularly in the domains of wound healing and tissue regeneration. Notably, exosomes derived from mesenchymal stem cells (MSCs) can be safely administered in the system, which is then adeptly uptaken and internalized by fibroblasts/epithelial cells, subsequently accelerating essential processes such as migration, proliferation, and collagen synthesis. Furthermore, exosomes released by immune cells, specifically macrophages, possess the capability to modulate inflammation and effectively diminish it in adjacent cells. Exosomes also act as carriers when integrated with a scaffold, leading to scarless healing of cutaneous wounds. This comprehensive review examines the role of exosomes in burn wound healing and their potential utility in regeneration and repair.
Collapse
Affiliation(s)
- Tasaduq Manzoor
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
- School of Life and Basic Sciences, Jaipur National University, Jagatpura, Jaipur, India
| | - Nida Farooq
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
| | - Arushi Sharma
- Centre for Biomedical Engineering, Indian Institute of Technology-Delhi, New Delhi, India
| | - Parvaiz A Shiekh
- Centre for Biomedical Engineering, Indian Institute of Technology-Delhi, New Delhi, India
| | - Amreena Hassan
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
| | - Lateef Ahmad Dar
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
| | - Junaid Nazir
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
| | - Meena Godha
- School of Life and Basic Sciences, Jaipur National University, Jagatpura, Jaipur, India
| | - Faheem A Sheikh
- Department of Nanotechnology, University of Kashmir, Srinagar, Kashmir, India
| | - Mudasir Bashir Gugjoo
- Veterinary Clinical Services Complex, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST- Srinagar, Kashmir, India
| | - Sahar Saleem
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India
| | - Syed Mudasir Ahmad
- Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST, Srinagar, Kashmir, 190006, India.
| |
Collapse
|
|
44
|
Barcelos SM, Rosa PMDS, Moura ABB, Villarroel CLP, Bridi A, Bispo ECI, Garcez EM, Oliveira GDS, Almeida MA, Malard PF, Peixer MAS, Pereira RW, de Alencar SA, Saldanha-Araujo F, Dallago BSL, da Silveira JC, Perecin F, Pogue R, Carvalho JL. Extracellular vesicles derived from bovine adipose-derived mesenchymal stromal cells enhance in vitro embryo production from lesioned ovaries. Cytotherapy 2024; 26:1141-1151. [PMID: 38904584 DOI: 10.1016/j.jcyt.2024.05.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 05/15/2024] [Accepted: 05/15/2024] [Indexed: 06/22/2024]
Abstract
BACKGROUND AND AIMS Ovum pick-up (OPU) is an intrinsic step of in vitro fertilization procedures. Nevertheless, it can cause ovarian lesions and compromise female fertility in bovines. Recently, we have shown that intraovarian injection of adipose-derived mesenchymal stromal cells (AD-MSCs) effectively preserves ovarian function in bovines. Given that MSC-derived extracellular vesicles (MSC-EVs) have been shown to recapitulate several therapeutic effects attributed to AD-MSCs and that they present logistic and regulatory advantages compared to AD-MSCs, we tested whether MSC-EVs would also be useful to treat OPU-induced lesions. METHODS MSC-EVs were isolated from the secretome of bovine AD-MSCs, using ultrafiltration (UF) and ultracentrifugation methods. The MSC-EVs were characterized according to concentration and mean particle size, morphology, protein concentration and EV markers, miRNA, mRNA, long noncoding RNA profile, total RNA yield and potential for induction of the proliferation and migration of bovine ovarian stromal cells. We then investigated whether intraovarian injection of MSC-EVs obtained by UF would reduce the negative effects of acute OPU-induced ovarian lesions in bovines. To do so, 20 animals were divided into 4 experimental groups (n = 5), submitted to 4 OPU cycles and different experimental treatments including vehicle only (G1), MSC-EVs produced by 7.5 × 106 AD-MSCs (G2), MSC-EVs produced by 2.5 × 106 AD-MSCs (G3) or 3 doses of MSC-EVs produced by 2.5 × 106 AD-MSCs, injected after OPU sessions 1, 2 and 3 (G4). RESULTS Characterization of the MSC-EVs revealed that the size of the particles was similar in the different isolation methods; however, the UF method generated a greater MSC-EV yield. MSC-EVs processed by both methods demonstrated a similar ability to promote cell migration and proliferation in ovarian stromal cells. Considering the higher yield and lower complexity of the UF method, UF-MSC-EVs were used in the in vivo experiment. We evaluated three therapeutic regimens for cows subjected to OPU, noting that the group treated with three MSC-EV injections (G4) maintained oocyte production and increased in vitro embryo production, compared to G1, which presented compromised embryo production following the OPU-induced lesions. CONCLUSIONS MSC-EVs have beneficial effects both on the migration and proliferation of ovarian stromal cells and on the fertility of bovines with follicular puncture injury in vivo.
Collapse
Affiliation(s)
- Stefhani Martins Barcelos
- Multidisciplinary Laboratory of Biosciences, Faculty of Medicine, University of Brasilia, Brasilia, DF, Brazil; Genomic Sciences and Biotechnology Program, Catholic University of Brasilia, Brasília, DF, Brazil
| | - Paola Maria da Silva Rosa
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil
| | - Ana Beatriz Bossois Moura
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil
| | | | - Alessandra Bridi
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil
| | | | - Emãnuella Melgaço Garcez
- Genomic Sciences and Biotechnology Program, Catholic University of Brasilia, Brasília, DF, Brazil
| | | | - Maria Alice Almeida
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil
| | | | | | | | - Sérgio Amorim de Alencar
- Genomic Sciences and Biotechnology Program, Catholic University of Brasilia, Brasília, DF, Brazil
| | - Felipe Saldanha-Araujo
- Department of Pharmacy, Faculty of Health Sciences, University of Brasilia, Brasilia, DF, Brazil
| | - Bruno Stéfano Lima Dallago
- Multidisciplinary Laboratory of Biosciences, Faculty of Medicine, University of Brasilia, Brasilia, DF, Brazil
| | - Juliano Coelho da Silveira
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil
| | - Felipe Perecin
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil
| | - Robert Pogue
- Genomic Sciences and Biotechnology Program, Catholic University of Brasilia, Brasília, DF, Brazil
| | - Juliana Lott Carvalho
- Multidisciplinary Laboratory of Biosciences, Faculty of Medicine, University of Brasilia, Brasilia, DF, Brazil; Genomic Sciences and Biotechnology Program, Catholic University of Brasilia, Brasília, DF, Brazil.
| |
Collapse
|
|
45
|
Gong X, Zhao Q, Zhang H, Liu R, Wu J, Zhang N, Zou Y, Zhao W, Huo R, Cui R. The Effects of Mesenchymal Stem Cells-Derived Exosomes on Metabolic Reprogramming in Scar Formation and Wound Healing. Int J Nanomedicine 2024; 19:9871-9887. [PMID: 39345908 PMCID: PMC11438468 DOI: 10.2147/ijn.s480901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 09/17/2024] [Indexed: 10/01/2024] Open
Abstract
Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.
Collapse
Affiliation(s)
- Xiangan Gong
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China
| | - Qian Zhao
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China
| | - Huimin Zhang
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China
| | - Rui Liu
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China
| | - Jie Wu
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China
| | - Nanxin Zhang
- School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China
| | - Yuanxian Zou
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China
| | - Wen Zhao
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China
| | - Ran Huo
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China
| | - Rongtao Cui
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China
| |
Collapse
|
|
46
|
Wu S, Zhou Z, Li Y, Jiang J. Advancements in diabetic foot ulcer research: Focus on mesenchymal stem cells and their exosomes. Heliyon 2024; 10:e37031. [PMID: 39286219 PMCID: PMC11403009 DOI: 10.1016/j.heliyon.2024.e37031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/11/2024] [Accepted: 08/26/2024] [Indexed: 09/19/2024] Open
Abstract
Diabetes represents a widely acknowledged global public health concern. Diabetic foot ulcer (DFU) stands as one of the most severe complications of diabetes, its occurrence imposing a substantial economic burden on patients, profoundly impacting their quality of life. Despite the deepening comprehension regarding the pathophysiology and cellular as well as molecular responses of DFU, the current therapeutic arsenal falls short of efficacy, failing to offer a comprehensive remedy for deep-seated chronic wounds and microvascular occlusions. Conventional treatments merely afford symptomatic alleviation or retard the disease's advancement, devoid of the capacity to effectuate further restitution of compromised vasculature and nerves. An escalating body of research underscores the prominence of mesenchymal stem cells (MSCs) owing to their paracrine attributes and anti-inflammatory prowess, rendering them a focal point in the realm of chronic wound healing. Presently, MSCs have been validated as a highly promising cellular therapeutic approach for DFU, capable of effectuating cellular repair, epithelialization, granulation tissue formation, and neovascularization by means of targeted differentiation, angiogenesis promotion, immunomodulation, and paracrine activities, thereby fostering wound healing. The secretome of MSCs comprises cytokines, growth factors, chemokines, alongside exosomes harboring mRNA, proteins, and microRNAs, possessing immunomodulatory and regenerative properties. The present study provides a systematic exposition on the etiology of DFU and elucidates the intricate molecular mechanisms and diverse functionalities of MSCs in the context of DFU treatment, thereby furnishing pioneering perspectives aimed at harnessing the therapeutic potential of MSCs for DFU management and advancing wound healing processes.
Collapse
Affiliation(s)
- ShuHui Wu
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - ZhongSheng Zhou
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yang Li
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jinlan Jiang
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
47
|
Gu Y, Mu Z, Chen Y, Wu C, Shi J, Bai N. Therapeutic potential of ADSCs in diabetic wounds: a proteomics-based approach. Front Cell Dev Biol 2024; 12:1468220. [PMID: 39345337 PMCID: PMC11427884 DOI: 10.3389/fcell.2024.1468220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Accepted: 08/26/2024] [Indexed: 10/01/2024] Open
Abstract
Background Diabetes mellitus (DM), a chronic metabolic disease characterized by elevated blood sugar, leads to delayed or non-healing wounds, increasing amputation risks, and placing a significant burden on patients and society. While extensive research has been conducted on adipose-derived stem cells (ADSCs) for promoting wound healing, there is a scarcity of studies focusing on diabetic wounds, particularly those employing proteomics and bioinformatics approaches. Objective This study aimed to investigate the mechanisms by which ADSCs promote diabetic wound healing using proteomics and bioinformatics techniques. Methods Healthy rat fat tissue was used to isolate ADSCs. A T2DM rat model with back wounds was established. The experimental group received ADSC injections around the wound, while the control group received PBS injections. Wound healing rates were documented and photographed on days 0, 3, 7, 10, and 14. On day 7, wound tissues were excised for HE and Masson's staining. Additionally, on day 7, tissues were analyzed for protein quantification using 4D-DIA, with subsequent GO and KEGG analyses for differentially expressed proteins (DEPs) and protein-protein interaction (PPI) network analysis using STRING database (String v11.5). Finally, Western blot experiments were performed on day 7 wounds to verify target proteins. Results and Conclusions In all measured days postoperatively, the wound healing rate was significantly higher in the ADSC group than in the PBS group (day 7: p < 0.001, day 10: p = 0.001, day 14: p < 0.01), except on day 3 (p > 0.05). Proteomic analysis identified 474 differentially expressed proteins, with 224 key proteins after PPI analysis (78 upregulated and 146 downregulated in the ADSC group). The main cellular locations of these proteins were "cellular anatomical entity" and "protein-containing complex", while the biological processes were "cellular processes" and "biological regulation". The primary molecular functions were "binding" and "catalytic activity", with GO enrichment focused on "Wnt-protein binding", "neural development", and "collagen-containing extracellular matrix". Further analysis of PPI network nodes using LASSO regression identified Thy1 and Wls proteins, significantly upregulated in the ADSC group, as potentially crucial targets for ADSC application in diabetic wound treatment.
Collapse
Affiliation(s)
- Yuan Gu
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Zelan Mu
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Yuanzheng Chen
- Department of Burns and Plastic Surgery, Emergency General Hospital, Beijing, China
| | - Can Wu
- Medical Cosmetic Plastic Surgery, Linyi People′s Hospital, Linyi, China
| | - Jie Shi
- Plastic and Cosmetic Surgery, People′s Hospital of Liaoning Province, Shenyang, China
| | - Nan Bai
- Medical Cosmetic Plastic Surgery, Linyi People′s Hospital, Linyi, China
| |
Collapse
|
|
48
|
Samarawickrama PN, Zhang G, Zhu E, Dong X, Nisar A, Zhu H, Ma Y, Zhou Z, Yang H, Gui L, Cao M, Li W, Chang Y, Zi M, Cui H, Duan Z, Zhang X, Li W, He Y. Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice. Theranostics 2024; 14:5429-5442. [PMID: 39310100 PMCID: PMC11413796 DOI: 10.7150/thno.100991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 08/16/2024] [Indexed: 09/25/2024] Open
Abstract
Background: Diabetic foot ulcers (DFUs) pose a substantial healthcare challenge due to their high rates of morbidity, recurrence, disability, and mortality. Current DFU therapeutics continue to grapple with multiple limitations. Senescent cells (SnCs) have been found to have a beneficial effect on acute wound healing, however, their roles in chronic wounds, such as DFU, remain unclear. Methods and results: We collected skin, fat, and muscle samples from clinical patients with DFU and lower limb fractures. RNA-sequencing combined with qPCR analyses on these samples demonstrate a significant accumulation of SnCs at DFU, as indicated by higher senescence markers (e.g., p16 and p21) and a senescence-associated secretory phenotype (SASP). We constructed a type 2 diabetic model of db/db mice, fed with a high-fat diet (Db-HFD), which were wounded using a 6 mm punch to the dorsal skin. HFD slightly affected wound healing in wild-type (WT) mice, but high glucose significantly delayed wound healing in the Db-HFD mice. We injected the mice with a previously developed fluorescent probe (XZ1208), which allows the detection of SnCs in vivo, and observed a strong senescence signal at the wound site of the Db-HFD mice. Contrary to the beneficial effects of SnCs in acute wound healing, our results demonstrated that clearance of SnCs using the senolytic compound ABT263 significantly accelerated wound healing in Db-HFD mice. Conclusion: Collectively, these findings suggest that SnCs critically accumulate at wound sites, delaying the healing process in DFUs. Thus, targeting SnCs with senolytic therapy represents a promising approach for DFU treatment, potentially improving the quality of life for patients with DFUs.
Collapse
Affiliation(s)
- Priyadarshani Nadeeshika Samarawickrama
- Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
- Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Guiqin Zhang
- Department of Endocrinology, the Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province), Kunming, Yunnan 650011, China
| | - Enfang Zhu
- Department of Endocrinology, the Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province), Kunming, Yunnan 650011, China
| | - Xin Dong
- Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
- Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
| | - Ayesha Nisar
- Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
- Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Hong Zhu
- Department of Endocrinology, the Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province), Kunming, Yunnan 650011, China
| | - Yuan Ma
- Department of Orthopedics, the Third People's Hospital of Yunnan Province, Kunming, Yunnan 650011, China
| | - Zheyan Zhou
- Department of Pathology, the Third People's Hospital of Yunnan Province, Kunming, Yunnan 650011, China
| | - Honglin Yang
- Department of Orthopedics, the Third People's Hospital of Yunnan Province, Kunming, Yunnan 650011, China
| | - Li Gui
- Department of Endocrinology, the Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province), Kunming, Yunnan 650011, China
| | - Mei Cao
- Department of Endocrinology, the Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province), Kunming, Yunnan 650011, China
| | - Wei Li
- Department of Endocrinology, the Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province), Kunming, Yunnan 650011, China
| | - Yu Chang
- Department of Endocrinology, the Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province), Kunming, Yunnan 650011, China
| | - Meiting Zi
- Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
- Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
| | - Haoling Cui
- Department of Endocrinology, the Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province), Kunming, Yunnan 650011, China
| | - Zhongping Duan
- Department of Endocrinology, the Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province), Kunming, Yunnan 650011, China
| | - Xuan Zhang
- Drug Discovery & Development Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Wen Li
- Department of Endocrinology, the Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province), Kunming, Yunnan 650011, China
| | - Yonghan He
- Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
- Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| |
Collapse
|
|
49
|
Peng H, Du F, Wang J, Wu Y, Wei Q, Chen A, Duan Y, Shi S, Zhang J, Yu S. Adipose-Derived Stem-Cell-Membrane-Coated PLGA-PEI Nanoparticles Promote Wound Healing via Efficient Delivery of miR-21. Pharmaceutics 2024; 16:1113. [PMID: 39339150 PMCID: PMC11434648 DOI: 10.3390/pharmaceutics16091113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 07/31/2024] [Accepted: 08/21/2024] [Indexed: 09/30/2024] Open
Abstract
miRNAs have been shown to be involved in the regulation of a variety of physiological and pathological processes, but their use in the treatment of diseases is still limited due to their instability. Biomimetic nanomaterials combine nanomaterials with cellular components that are readily modifiable and biocompatible, making them an emerging miRNA delivery vehicle. In this study, adipose-derived MSC membranes were wrapped around PLGA-PEI loaded with miR-21 through co-extrusion and later transplanted into C57BL/6 mice wounds. The wound-healing rate, epithelialization, angiogenesis, and collagen deposition were assessed after treatment and corroborated in vitro. Our study demonstrated that m/NP/miR-21 can promote wound healing in terms of epithelialization, dermal reconstruction, and neovascularization, and it can regulate the corresponding functions of keratinocytes, fibroblasts, and vascular endothelial cells. m/NP/miR-21 can inhibit the expression of PTEN, a gene downstream of miR-21, and increase the phosphorylation activation of AKT, which can then regulate the functions of fibroblasts. In conclusion, this provides a new approach to therapy for skin wounds using microRNA transporters and biomimetic nanoparticles.
Collapse
Affiliation(s)
- Huiyu Peng
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Fangzhou Du
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Jingwen Wang
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Yue Wu
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Qian Wei
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Aoying Chen
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Yuhan Duan
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Shuaiguang Shi
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
| | - Jingzhong Zhang
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
- School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, China
| | - Shuang Yu
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
- School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, China
| |
Collapse
|
|
50
|
Sun Y, Zhang S, Shen Y, Lu H, Zhao X, Wang X, Wang Y, Wang T, Liu B, Yao L, Wen J. Therapeutic application of mesenchymal stem cell-derived exosomes in skin wound healing. Front Bioeng Biotechnol 2024; 12:1428793. [PMID: 39161350 PMCID: PMC11330766 DOI: 10.3389/fbioe.2024.1428793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 07/25/2024] [Indexed: 08/21/2024] Open
Abstract
Wound healing is a complicated obstacle, especially for chronic wounds. Mesenchymal stem cell-derived exosomes may be a promising cell-free approach for treating skin wound healing. Exosomes can accelerate wound healing by attenuating inflammation, promoting angiogenesis, cell proliferation, extracellular matrix production and remodeling. However, many issues, such as off-target effects and high degradation of exosomes in wound sites need to be addressed before applying into clinical therapy. Therefore, the bioengineering technology has been introduced to modify exosomes with greater stability and specific therapeutic property. To prolong the function time and the local concentration of exosomes in the wound bed, the use of biomaterials to load exosomes emerges as a promising strategy. In this review, we summarize the biogenesis and characteristics of exosomes, the role of exosomes in wound healing, and the therapeutic applications of modified-exosomes in wound healing. The challenges and prospects of exosomes in wound healing are also discussed.
Collapse
Affiliation(s)
- Yunhan Sun
- School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Shun Zhang
- School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yukai Shen
- School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Haoyang Lu
- School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xincan Zhao
- School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xin Wang
- School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yongkai Wang
- School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Taiping Wang
- School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Bing Liu
- School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Lan Yao
- Eye Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Jie Wen
- School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| |
Collapse
|