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Zhao L, Li H, Liu Z, Wang Z, Xu D, Zhang J, Ran J, Mo H, Hu L. Copper ions induces ferroptosis in Staphylococcus aureus and promotes healing of MRSA-induced wound infections. Microbiol Res 2025; 296:128122. [PMID: 40024210 DOI: 10.1016/j.micres.2025.128122] [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: 11/21/2024] [Revised: 01/09/2025] [Accepted: 02/24/2025] [Indexed: 03/04/2025]
Abstract
The emergence of multidrug-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), poses a significant threat to public health, necessitating new antimicrobial strategies. Here, we demonstrate that low doses of copper sulfate (CuSO4) exhibit potent bactericidal effects against both S. aureus and MRSA by inducing ferroptosis. CuSO4 treatment causes bacterial cell membrane perforation, increases intracellular free copper (Cu+) and ferrous ions (Fe2+), elevates reactive oxygen species (ROS) production and lipid peroxidation, and triggers the intracellular Fenton reaction. The use of ROS scavengers, copper chelators, iron chelators, and iron oxidase inhibitors attenuated ROS levels and lipid peroxidation, reducing Cu2+-mediated cell death, confirming the role of ferroptosis. Proteomic analysis revealed that Cu2+ enhances the expression of Fur protein, mediates iron release from intracellular stores, and inhibits glutathione biosynthesis. Furthermore, we developed a sodium alginate hydrogel loaded with CuSO4 (Cu-SA), which significantly improved wound healing and reduced inflammation and organ damage in an MRSA-infected mouse skin model. Our findings suggest that Cu2+-induced ferroptosis offers a promising alternative to traditional antibiotics for treating MRSA infections, providing a novel strategy to combat antibiotic resistance in S. aureus.
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Affiliation(s)
- Lili Zhao
- School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China
| | - Hongbo Li
- School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.
| | - Zhenbin Liu
- School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China
| | - Zhen Wang
- School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China; Shaanxi Agricultural Products Processing Technology Research Institute, Xi'an 710021, China; School of Food Science, Henan Institute of Science and Technology, Xinxiang 453003, China
| | - Dan Xu
- School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China
| | - Jiayi Zhang
- School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China; Shaanxi Agricultural Products Processing Technology Research Institute, Xi'an 710021, China
| | - Junjian Ran
- School of Food Science, Henan Institute of Science and Technology, Xinxiang 453003, China
| | - Haizhen Mo
- School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China
| | - Liangbin Hu
- School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.
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2
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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.
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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.
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3
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Xiang B, Zhang S, Zhao IS, Gan X, Zhang Y. Microenvironmental Modulation for Therapeutic Efficacy of Extracellular Vesicles. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2503027. [PMID: 40145773 PMCID: PMC12079496 DOI: 10.1002/advs.202503027] [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] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 03/04/2025] [Indexed: 03/28/2025]
Abstract
Extracellular vesicles (EVs) hold significant promise for the prevention and treatment of various diseases. However, the translation of EV-based therapies into clinical practice faces considerable challenges, particularly in terms of production yield and therapeutic efficacy. Recent studies have emphasized the heterogeneity of EVs and the influence of parental cell microenvironmental signals on their biogenesis, cargo composition, and therapeutic outcomes. This review offers a comprehensive overview of strategies to optimize the therapeutic efficacy of EVs through physical, biochemical, and mechanical modulation. Additionally, it explores how microenvironmental signals affect EV cargoes and the mechanisms by which these signals can improve therapeutic efficacy. The review also addresses current challenges and potential solutions to accelerate the clinical translation of EV therapies. Ultimately, it highlights the potential of microenvironmental modulation in unlocking the full therapeutic capacity of EVs, providing key insights into their production and clinical use for treating various diseases.
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Affiliation(s)
- Bilu Xiang
- School of DentistryShenzhen University Medical SchoolShenzhen518055China
- Institute of Oral ScienceShenzhen UniversityShenzhen518055China
| | - Shiying Zhang
- School of DentistryShenzhen University Medical SchoolShenzhen518055China
| | - Irene Shuping Zhao
- School of DentistryShenzhen University Medical SchoolShenzhen518055China
- Institute of Oral ScienceShenzhen UniversityShenzhen518055China
| | - Xueqi Gan
- State Key Laboratory of Oral DiseaseNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041China
| | - Yang Zhang
- School of DentistryShenzhen University Medical SchoolShenzhen518055China
- Institute of Oral ScienceShenzhen UniversityShenzhen518055China
- School of Biomedical EngineeringShenzhen University Medical SchoolShenzhen518055China
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4
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Yuan Y, Cao K, Gao P, Wang Y, An W, Dong Y. Extracellular vesicles and bioactive peptides for regenerative medicine in cosmetology. Ageing Res Rev 2025; 107:102712. [PMID: 40032214 DOI: 10.1016/j.arr.2025.102712] [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: 11/08/2024] [Revised: 01/10/2025] [Accepted: 02/25/2025] [Indexed: 03/05/2025]
Abstract
As life quality improves and the life pressure increases, people's awareness of maintaining healthy skin and hair grows. However, the use of bioactive peptides in regenerative medical aesthetics is often constrained by the high molecular weight, which impedes skin penetration. In contrast, extracellular vesicles not only possess regenerative properties but also serve as effective carriers for bioactive peptides. Given their anti-inflammatory and bactericidal properties, capacity to promote angiogenesis, optimize collagen alignment, facilitate re-epithelialization and stimulate hair growth, extracellular vesicles become an emerging and promising solution for skin regeneration treatments. The combination of peptides and extracellular vesicles enhances therapeutic efficacy and improves the bioavailability of bioactive peptides. In this review, we summarize the functions of bioactive peptides and plant- and animal-derived extracellular vesicles in regenerative medicine with cosmetology, along with examples of their combined applications. Additionally, we provide an overview of peptides and extracellular vesicles currently available on the market and in clinical practice, discussing the challenges and solutions associated with their use.
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Affiliation(s)
- Yize Yuan
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
| | - Kailu Cao
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
| | - Peifen Gao
- National Vaccine & Serum Institute, China National Biotech Group, Sinopharm Group, Beijing 101111, China
| | - Yinan Wang
- National Vaccine & Serum Institute, China National Biotech Group, Sinopharm Group, Beijing 101111, China
| | - Wenlin An
- National Vaccine & Serum Institute, China National Biotech Group, Sinopharm Group, Beijing 101111, China.
| | - Yiyang Dong
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
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5
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Keshtkar S, Asvar Z, Najafi H, Heidari M, Kaviani M, Sarvestani FS, Tamaddon AM, Sadati MS, Hamidizadeh N, Azarpira N. Exosomes as natural vectors for therapeutic delivery of bioactive compounds in skin diseases. Front Pharmacol 2025; 16:1485769. [PMID: 40356952 PMCID: PMC12066514 DOI: 10.3389/fphar.2025.1485769] [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: 08/24/2024] [Accepted: 04/07/2025] [Indexed: 05/15/2025] Open
Abstract
Skin diseases are a broad category of diseases and each has complex conditions, which makes it challenging for dermatologists to provide targeted treatment. Exosomes are natural vesicles secreted by cells and play a key role in cell communication. Due to their unique characteristics, including inherent stability, minimal immunogenicity, high biocompatibility, and exceptional ability to penetrate cells, exosomes are being explored as potential delivery vehicles for therapeutics across various diseases including skin problems. Utilizing exosomes for drug delivery in skin diseases can improve treatment outcomes and reduce the side effects of traditional drug delivery methods. Indeed, exosomes can be engineered or utilized as an innovative approach to deliver therapeutic agents such as small molecule drugs, genes, or proteins specifically to affected skin cells. In addition to targeting specific skin cells or tissues, these engineered exosome-based nanocarriers can reduce off-target effects and improve drug efficacy. Hence, this article highlights the transformative potential of this technology in revolutionizing drug delivery in dermatology and improving patient outcomes.
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Affiliation(s)
- Somayeh Keshtkar
- Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Asvar
- Nanotechnology School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Haniyeh Najafi
- Department of Pharmaceutical Nanotechnology, Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mozhdeh Heidari
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Kaviani
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Ali Mohammad Tamaddon
- Department of Pharmaceutical Nanotechnology, Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Sadat Sadati
- Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nasrin Hamidizadeh
- Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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6
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Abbasi R, Alamdari-Mahd G, Maleki-Kakelar H, Momen-Mesgin R, Ahmadi M, Sharafkhani M, Rezaie J. Recent advances in the application of engineered exosomes from mesenchymal stem cells for regenerative medicine. Eur J Pharmacol 2025; 989:177236. [PMID: 39753159 DOI: 10.1016/j.ejphar.2024.177236] [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: 10/25/2024] [Revised: 12/14/2024] [Accepted: 12/23/2024] [Indexed: 01/12/2025]
Abstract
Exosomes, cell-derived vesicles produced by cells, are fascinating and drawing growing interest in biomedical exploration due to their exceptional properties. There is intriguing evidence that exosomes are involved in major biological processes, including diseases and regeneration. Exosomes from mesenchymal stem cells (MSCs) have shown promising outcomes in regenerative medicine. Numerous studies suggest that exosomes have several advantages over conventional synthetic nanocarriers, opening novel frontiers for innovative drug delivery. Regenerative medicine has demonstrated the profound therapeutic outcomes of engineered or loaded exosomes from MSCs. Different methods are being used to modify or/load exosomes. These exosomes can improve cell signaling pathways for bone and cartilage diseases, liver diseases, nerve tissues, kidney diseases, skin tissue, and cardiovascular diseases. Despite extensive research, clinical translation of these exosomes remains a challenge. The optimization of cargo loading methods, efficiency, physiological stability, and the isolation and characterization of exosomes present some challenges. The upcoming examination should include the development of large-scale, quality-controllable production approaches, the modification of drug loading approaches, and numerous in vivo investigations and clinical trials. Here, we provided an informative overview of the extracellular vesicles and modification/loading methods of exosomes. We discuss the last exosome research on regeneration disorders, highlighting the therapeutic applications of MSCs-derived exosomes. We also highlight future directions and challenges, underscoring the significance of addressing the main questions in the field.
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Affiliation(s)
- Reza Abbasi
- Department of Biology, Urmia University, Urmia, Iran
| | - Ghazal Alamdari-Mahd
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Hadi Maleki-Kakelar
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
| | | | - Mahdi Ahmadi
- Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohaddeseh Sharafkhani
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Jafar Rezaie
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
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7
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Morabbi A, Karimian M. Therapeutic potential of exosomal lncRNAs derived from stem cells in wound healing: focusing on mesenchymal stem cells. Stem Cell Res Ther 2025; 16:62. [PMID: 39934913 PMCID: PMC11816792 DOI: 10.1186/s13287-025-04200-0] [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: 07/12/2024] [Accepted: 01/30/2025] [Indexed: 02/13/2025] Open
Abstract
The self-renewal ability and multipotency of stem cells give them great potential for use in wound healing. Stem cell-derived exosomes, owing to their close biological resemblance to their parent cells, offer a more efficient, safer, and economical approach for facilitating cellular communication and interactions within different environments. This potential makes them particularly valuable in the treatment of both acute and chronic wounds, such as lacerations, burns, and diabetic ulcers. Long non-coding RNAs (lncRNAs) enclosed in exosomes, as one of the leading actors of these extracellular microvesicles, through interaction with miRNAs and regulation of various signaling pathways involved in inflammation, angiogenesis, cell proliferation, and migration, could heal the wounds. Exosome-derived lncRNAs from stem cells facilitate extracellular matrix remodeling through interaction between macrophages and fibroblasts. Moreover, alongside regulating the expression of inflammatory cytokines, controlling reactive oxygen species levels, and enhancing autophagic activity, they also modulate immune responses to support wound healing. Regulating the expression of genes and signaling pathways related to angiogenesis, by increasing blood supply and accelerating the delivery of essential substances to the wound environment, is another effect exosomal lncRNAs derived from stem cells for wound healing. These lncRNAs can also enhance skin wound healing by regulating homeostasis, increasing the proliferation and differentiation of cells involved in the wound-healing process, and enhancing fibroblast viability and migration to the injury site. Ultimately, exosome-derived lncRNAs from stem cells offer valuable and novel insights into the molecular mechanisms underlying improved wound healing. They can pave the way for potential therapeutic strategies, fostering further research for a better future. Meanwhile, exosomes derived from mesenchymal stem cells, due to their exceptional regenerative properties, as well as the lncRNAs derived from these exosomes, have emerged as one of the innovative tools in wound healing. This review article aims to narrate the cellular and molecular roles of exosome-derived lncRNAs from stem cells in enhancing wound healing with a focus on mesenchymal stem cells.
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Affiliation(s)
- Ali Morabbi
- Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, 47416-95447, Iran
| | - Mohammad Karimian
- Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, 47416-95447, Iran.
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8
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Feng Z, Yang Y, Liu XZ, Sun HJ, Wen BY, Chen Z, Wei B. Application of cell therapy in rheumatoid Arthritis: Focusing on the immunomodulatory strategies of Mesenchymal stem cells. Int Immunopharmacol 2025; 147:114017. [PMID: 39778278 DOI: 10.1016/j.intimp.2025.114017] [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: 11/16/2024] [Revised: 12/24/2024] [Accepted: 01/02/2025] [Indexed: 01/11/2025]
Abstract
Rheumatoid arthritis (RA) is a common chronic autoimmune disease that primarily affects the joints, leading to synovial inflammation and hyperplasia, which subsequently causes joint pain, swelling, and damage. The microenvironment of RA is characterized by hypoxia, high reactive oxygen species (ROS), low pH, and levels of high inflammatory factors. Traditional treatments only partially alleviate symptoms and often cause various adverse reactions with long-term use. Therefore, there is an urgent need for safer and more effective treatments. In recent years, mesenchymal stem cells (MSCs) have shown significant potential in treating RA due to their diverse immunomodulatory mechanisms. MSCs paracrine a variety of soluble factors to improve the inflammatory microenvironment in RA patients by inhibiting T cell proliferation or inducing T cell differentiation to regulatory T cells (Tregs), inhibiting B cell proliferation and differentiation and immunoglobulin production, prompting macrophage polarization toward an anti-inflammatory phenotype, and inhibiting neutrophil recruitment and preventing the maturation of dendritic cells (DCs). This review summarizes the immunomodulatory effects of MSCs in RA and their application in animal models and clinical trials. Although the immunomodulatory mechanisms of MSCs are not yet fully elucidated, their significant potential in RA treatment has been widely recognized. Future research should further explore the immunomodulatory mechanisms of MSCs and optimize their functions in different pathological microenvironments to develop more effective and safer therapeutic strategies.
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Affiliation(s)
- Zhi Feng
- Institute of Translational Medicine, School of Basic Medical, Hengyang Medical College, University of South China, Hengyang, Hunan 42100l, China
| | - Ying Yang
- Department of Specialty Medicine, School of Public Health, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Xiang-Zhuo Liu
- Institute of Translational Medicine, School of Basic Medical, Hengyang Medical College, University of South China, Hengyang, Hunan 42100l, China
| | - Hui-Jiao Sun
- Institute of Translational Medicine, School of Basic Medical, Hengyang Medical College, University of South China, Hengyang, Hunan 42100l, China
| | - Bo-Ya Wen
- Institute of Translational Medicine, School of Basic Medical, Hengyang Medical College, University of South China, Hengyang, Hunan 42100l, China
| | - Zhi Chen
- Institute of Translational Medicine, School of Basic Medical, Hengyang Medical College, University of South China, Hengyang, Hunan 42100l, China
| | - Bo Wei
- Institute of Translational Medicine, School of Basic Medical, Hengyang Medical College, University of South China, Hengyang, Hunan 42100l, China.
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9
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Yadav VK, Pramanik S, Alghamdi S, Atwah B, Qusty NF, Babalghith AO, Solanki VS, Agarwal N, Gupta N, Niazi P, Patel A, Choudhary N, Zairov R. Therapeutic Innovations in Nanomedicine: Exploring the Potential of Magnetotactic Bacteria and Bacterial Magnetosomes. Int J Nanomedicine 2025; 20:403-444. [PMID: 39816378 PMCID: PMC11734620 DOI: 10.2147/ijn.s462031] [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: 09/24/2024] [Accepted: 12/07/2024] [Indexed: 01/18/2025] Open
Abstract
Nanotechnology has emerged as a revolutionary domain with diverse applications in medicine, and one of the noteworthy developments is the exploration of bacterial magnetosomes acquired from magnetotactic bacteria (MTB) for therapeutic purposes. The demand for natural nanomaterials in the biomedical field is continuously increasing due to their biocompatibility and eco-friendly nature. MTB produces uniform, well-ordered magnetic nanoparticles inside the magnetosomes, drawing attention due to their unique and remarkable features. MTB and magnetosomes have gained popularity in cancer treatment and diagnosis, especially in magnetic resonance imaging. Distinctive features highlighted include advancements in extraction, characterization, and functionalization techniques, alongside breakthroughs in utilizing MTB-based magnetosomes as contrast agents in imaging, biocompatible drug carriers, and tools for minimally invasive therapies. The biocompatible nature, functionalizing of the surface of bacterial magnetosomes, and response to the external magnetic field make them a potential candidate for the theragnostic purpose of MTB and magnetosomes. In the present review, emphasis has been given to the foundation of magnetosomes at a genetic level, mass production of magnetosomes, etc. Further authors have reviewed the various functionalization methods of the magnetosomes for cancer treatment. Finally, the authors have reviewed the recent advancements in MTB and magnetosome-based cancer detection, diagnosis, and treatment. Challenges such as scalability, long-term safety, and clinical translation are also discussed, presenting a roadmap for future research exploiting MTBs and magnetosomes' unique properties.
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Affiliation(s)
- Virendra Kumar Yadav
- Marwadi University Research Center, Department of Microbiology, Faculty of Sciences, Marwadi University, Rajkot, Gujarat, 360003, India
| | - Sheersha Pramanik
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu, 600036, India
| | - Saad Alghamdi
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Banan Atwah
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Naeem F Qusty
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ahmad O Babalghith
- Medical Genetics Department, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Vijendra Singh Solanki
- Department of Chemistry, Institute of Science and Research (ISR), IPS Academy, Indore, India
| | - Neha Agarwal
- Department of Chemistry, Navyug Kanya Mahavidyalaya, University of Lucknow, Lucknow, Uttar Pradesh, India
| | - Nishant Gupta
- Department of Engineering and Medical Devices, River Engineering Pvt Ltd, Ecotech-III, Greater Noida, U.p., India
| | - Parwiz Niazi
- Department of Biology, Faculty of Education, Kandahar University, Kandahar, Afghanistan
| | - Ashish Patel
- Department of Lifesciences, Hemchandracharya North Gujarat University, Patan, Gujarat, 384265, India
| | - Nisha Choudhary
- Department of Lifesciences, Hemchandracharya North Gujarat University, Patan, Gujarat, 384265, India
| | - Rustem Zairov
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center RAS, Kazan, Russian Federation
- Aleksander Butlerov Institute of Chemistry, Kazan Federal University, Kazan, Russian Federation
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10
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Wang Y, Chen H, Xie L, Liu J, Zhang L, Yu J. Swarm Autonomy: From Agent Functionalization to Machine Intelligence. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2025; 37:e2312956. [PMID: 38653192 PMCID: PMC11733729 DOI: 10.1002/adma.202312956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 04/17/2024] [Indexed: 04/25/2024]
Abstract
Swarm behaviors are common in nature, where individual organisms collaborate via perception, communication, and adaptation. Emulating these dynamics, large groups of active agents can self-organize through localized interactions, giving rise to complex swarm behaviors, which exhibit potential for applications across various domains. This review presents a comprehensive summary and perspective of synthetic swarms, to bridge the gap between the microscale individual agents and potential applications of synthetic swarms. It is begun by examining active agents, the fundamental units of synthetic swarms, to understand the origins of their motility and functionality in the presence of external stimuli. Then inter-agent communications and agent-environment communications that contribute to the swarm generation are summarized. Furthermore, the swarm behaviors reported to date and the emergence of machine intelligence within these behaviors are reviewed. Eventually, the applications enabled by distinct synthetic swarms are summarized. By discussing the emergent machine intelligence in swarm behaviors, insights are offered into the design and deployment of autonomous synthetic swarms for real-world applications.
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Affiliation(s)
- Yibin Wang
- School of Science and EngineeringThe Chinese University of Hong KongShenzhen518172China
- Shenzhen Institute of Artificial Intelligence and Robotics for SocietyShenzhen518172China
| | - Hui Chen
- School of Science and EngineeringThe Chinese University of Hong KongShenzhen518172China
- Shenzhen Institute of Artificial Intelligence and Robotics for SocietyShenzhen518172China
| | - Leiming Xie
- School of Science and EngineeringThe Chinese University of Hong KongShenzhen518172China
- Shenzhen Institute of Artificial Intelligence and Robotics for SocietyShenzhen518172China
| | - Jinbo Liu
- School of Science and EngineeringThe Chinese University of Hong KongShenzhen518172China
- Shenzhen Institute of Artificial Intelligence and Robotics for SocietyShenzhen518172China
| | - Li Zhang
- Department of Mechanical and Automation EngineeringThe Chinese University of Hong KongHong Kong999077China
| | - Jiangfan Yu
- School of Science and EngineeringThe Chinese University of Hong KongShenzhen518172China
- Shenzhen Institute of Artificial Intelligence and Robotics for SocietyShenzhen518172China
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11
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Liang QL, Liu H, Wang T, Lau CH, Wang J, Mo ZY, Zhou ZM, Zhou ZY, Zhu H, Chen G, Tong S. UV radiation enhanced encapsulation of superparamagnetic iron oxide nanoparticles (MNPs) in microparticles derived from tumor repopulating cells. Biochem Biophys Res Commun 2024; 741:151050. [PMID: 39586131 DOI: 10.1016/j.bbrc.2024.151050] [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: 09/18/2024] [Revised: 11/06/2024] [Accepted: 11/21/2024] [Indexed: 11/27/2024]
Abstract
Extracellular vesicles (EVs) such as microparticles secreted by the cells can be manipulated and used for delivering therapeutic drugs to target and eradicate cancer cells. However, high encapsulation efficiency and mass production of the microparticles remain difficult to achieve. Efficient and targeted delivery to cancer cells is another hurdle to be addressed. To overcome these issues, we integrated superparamagnetic iron oxide nanoparticles (MNPs) with microparticles. First of all, exposure of highly aggressive tumor-repopulating cells (TRC) to UV radiation dramatically improved microparticle production. These TRC cells were selected from diverse cancer cell lines that are 3D culturing in soft fibrin gel. These microparticles derived from 3D-cultured TRCs have lower membrane stiffness than 2D-cultured cells. Ferrozine assay showed that endocytosis and encapsulation of MNPs during microparticle production were higher in 3D-cultured TRC cells than in 2D cultured cells. Packaging of MNPs into microparticles also enhanced cellular uptake of MNPs without inducing cytotoxicity to treated cells. Compared to the naked MNPs, ex vivo fluorescence imaging shows that mice tail-vein injected with microparticle-encapsulated MNPs displayed continuous increments of intratumoral accumulation of MNPs. Furthermore, MRI images revealed a higher T2 contrast and an uneven distribution of the T2 contrast in the tumor of mice tail-vein injected with microparticle-encapsulated MNPs than naked MNPs. This study provides a new platform for cancer imaging by integrating MNPs and microparticles derived from tumor-repopulating cells.
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Affiliation(s)
- Qing-Le Liang
- Department of Clinical Laboratory Medicine, Chongqing University Jiangjin Hospital, Chongqing, China
| | - He Liu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Tao Wang
- Department of Biology, College of Science, Shantou University, Shantou, Guangdong, China
| | - Cia-Hin Lau
- Department of Biology, College of Science, Shantou University, Shantou, Guangdong, China
| | - Jianchao Wang
- Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Zheng-Ying Mo
- Department of Oncology, Tai-He Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Zhang-Ming Zhou
- Department of Neurosurgery, Dujiangyan Medical Center, Chengdu, China
| | - Zhe-Yu Zhou
- Department of Radiology, Tai-He Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Haibao Zhu
- Department of Biology, College of Science, Shantou University, Shantou, Guangdong, China; Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, Guangdong, China; Shantou Key Laboratory of Marine Microbial Resources and Interactions with Environment, Shantou University, Shantou, Guangdong, China.
| | - Gang Chen
- Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.
| | - Sheng Tong
- Department of Biomedical Engineering, University of Kentucky, USA.
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12
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Nouri S, Shokraneh S, Fatehi Shalamzari P, Ahmed MH, Radi UK, Idan AH, Ebrahimi MJ, Moafi M, Gholizadeh N. Application of Mesenchymal Stem Cells and Exosome alone or Combination Therapy as a Treatment Strategy for Wound Healing. Cell Biochem Biophys 2024; 82:3209-3222. [PMID: 39068609 DOI: 10.1007/s12013-024-01448-w] [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] [Accepted: 07/17/2024] [Indexed: 07/30/2024]
Abstract
The process of wound healing consists of multiple phases, and any disruptions in these phases can lead to the wound becoming chronic and impose heavy financial and psychological costs on the patient and a huge economic burden on the country's healthcare system. Various treatments such as drugs, matrix and scaffolds, blood products, cell therapy, and a combination of these treatments are used for wound healing. The use of mesenchymal stem cells (MSCs) is one of these methods that have produced appropriate responses in the healing of patients' wounds. MSCs by secreting growth factors, cytokines, chemokines, and RNAs elicit changes in cell proliferation, migration, growth, signaling, immunomodulation, and wound re-epithelialization process, and as a result, accelerate wound closure and wound healing. These cells can be isolated from different body sources with different cell characteristics and used directly on the wound site or by injection. In addition, MSCs-derived exosomes have attracted growing attention due to circumventing concerns relating to the direct use of MSCs. To increase the performance of MSCs, they can be used together with other compounds such as platelets, matrices, or scaffolds. This study examined the functions of MSCs in wound healing, as well as the vesicles they secrete, cellular and molecular mechanisms, and combined treatments with MSCs for wound healing.
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Affiliation(s)
- Soheil Nouri
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | | | | | | | - Usama Kadem Radi
- Collage of Pharmacy, National University of Science and Technology, Dhi Qar, 64001, Iraq
| | | | - Mohammad Javad Ebrahimi
- Cell Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maral Moafi
- Cell Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasim Gholizadeh
- Department of Dermatology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
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13
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Soltanmohammadi F, Gharehbaba AM, Zangi AR, Adibkia K, Javadzadeh Y. Current knowledge of hybrid nanoplatforms composed of exosomes and organic/inorganic nanoparticles for disease treatment and cell/tissue imaging. Biomed Pharmacother 2024; 178:117248. [PMID: 39098179 DOI: 10.1016/j.biopha.2024.117248] [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: 05/18/2024] [Revised: 07/30/2024] [Accepted: 07/30/2024] [Indexed: 08/06/2024] Open
Abstract
Exosome-nanoparticle hybrid nanoplatforms, can be prepared by combining exosomes with different types of nanoparticles. The main purpose of combining exosomes with nanoparticles is to overcome the limitations of using each of them as drug delivery systems. Using nanoparticles for drug delivery has some limitations, such as high immunogenicity, poor cellular uptake, low biocompatibility, cytotoxicity, low stability, and rapid clearance by immune cells. However, using exosomes as drug delivery systems also has its own drawbacks, such as poor encapsulation efficiency, low production yield, and the inability to load large molecules. These limitations can be addressed by utilizing hybrid nanoplatforms. Additionally, the use of exosomes allows for targeted delivery within the hybrid system. Exosome-inorganic/organic hybrid nanoparticles may be used for both therapy and diagnosis in the future. This may lead to the development of personalized medicine using hybrid nanoparticles. However, there are a few challenges associated with this. Surface modifications, adding functional groups, surface charge adjustments, and preparing nanoparticles with the desired size are crucial to the possibility of preparing exosome-nanoparticle hybrids. Additional challenges for the successful implementation of hybrid platforms in medical treatments and diagnostics include scaling up the manufacturing process and ensuring consistent quality and reproducibility across various batches. This review focuses on various types of exosome-nanoparticle hybrid systems and also discusses the preparation and loading methods for these hybrid nanoplatforms. Furthermore, the potential applications of these hybrid nanocarriers in drug/gene delivery, disease treatment and diagnosis, and cell/tissue imaging are explained.
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Affiliation(s)
- Fatemeh Soltanmohammadi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Adel Mahmoudi Gharehbaba
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Rajabi Zangi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Khosro Adibkia
- Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yousef Javadzadeh
- Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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14
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Chen Y, Hou S. Targeted treatment of rat AKI induced by rhabdomyolysis using BMSC derived magnetic exosomes and its mechanism. NANOSCALE ADVANCES 2024; 6:4180-4195. [PMID: 39114150 PMCID: PMC11304081 DOI: 10.1039/d4na00334a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 06/11/2024] [Indexed: 08/10/2024]
Abstract
Introduction: rhabdomyolysis (RM) is a serious syndrome. A large area of muscle injury and dissolution induces acute kidney injury (AKI), which results in a high incidence and mortality rate. Exosomes released by mesenchymal stem cells (MSCs) have been used to treat AKI induced by rhabdomyolysis and have shown regenerative effects. However, the most serious drawbacks of these methods are poor targeting and a low enrichment rate after systemic administration. Methods: in this study, we demonstrated that magnetic exosomes derived from bone marrow mesenchymal stem cells (BMSCs) can directly target damaged muscles rather than kidneys using an external magnetic field. Results: magnetic navigation exosomes reduced the dissolution of damaged muscles, greatly reduced the release of cellular contents, slowed the development of AKI. Discussion: in summary, our proposed method can overcome the shortcomings of poor targeting in traditional exosome therapy. Moreover, in the rhabdomyolysis-induced AKI model, we propose for the first time an exosome therapy mode that directly targets damaged muscles through magnetic navigation.
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Affiliation(s)
- Yuling Chen
- Institute of Disaster and Emergency Medicine, Tianjin University Tianjin China
- Tianjin Key Laboratory of Disaster Medicine Technology Tianjin China
| | - Shike Hou
- Institute of Disaster and Emergency Medicine, Tianjin University Tianjin China
- Tianjin Key Laboratory of Disaster Medicine Technology Tianjin China
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15
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Wu D, Zhao X, Xie J, Yuan R, Li Y, Yang Q, Cheng X, Wu C, Wu J, Zhu N. Physical modulation of mesenchymal stem cell exosomes: A new perspective for regenerative medicine. Cell Prolif 2024; 57:e13630. [PMID: 38462759 PMCID: PMC11294442 DOI: 10.1111/cpr.13630] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 01/29/2024] [Accepted: 02/26/2024] [Indexed: 03/12/2024] Open
Abstract
Mesenchymal stem cell-derived exosomes (MSC-Exo) offer promising therapeutic potential for various refractory diseases, presenting a novel therapeutic strategy. However, their clinical application encounters several obstacles, including low natural secretion, uncontrolled biological functions and inherent heterogeneity. On the one hand, physical stimuli can mimic the microenvironment dynamics where MSC-Exo reside. These factors influence not only their secretion but also, significantly, their biological efficacy. Moreover, physical factors can also serve as techniques for engineering exosomes. Therefore, the realm of physical factors assumes a crucial role in modifying MSC-Exo, ultimately facilitating their clinical translation. This review focuses on the research progress in applying physical factors to MSC-Exo, encompassing ultrasound, electrical stimulation, light irradiation, intrinsic physical properties, ionizing radiation, magnetic field, mechanical forces and temperature. We also discuss the current status and potential of physical stimuli-affected MSC-Exo in clinical applications. Furthermore, we address the limitations of recent studies in this field. Based on this, this review provides novel insights to advance the refinement of MSC-Exo as a therapeutic approach in regenerative medicine.
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Affiliation(s)
- Dan Wu
- Department of DermatologyHuashan Hospital, Fudan UniversityShanghaiChina
| | - Xiansheng Zhao
- Department of DermatologyHuashan Hospital, Fudan UniversityShanghaiChina
| | - Jiaheng Xie
- Department of Plastic SurgeryXiangya Hospital, Central South UniversityChangshaHunanChina
| | - Ruoyue Yuan
- Department of DermatologyHuashan Hospital, Fudan UniversityShanghaiChina
| | - Yue Li
- Department of DermatologyHuashan Hospital, Fudan UniversityShanghaiChina
| | - Quyang Yang
- Department of DermatologyHuashan Hospital, Fudan UniversityShanghaiChina
| | - Xiujun Cheng
- Department of DermatologyHuashan Hospital, Fudan UniversityShanghaiChina
| | - Changyue Wu
- Department of DermatologyHuashan Hospital, Fudan UniversityShanghaiChina
| | - Jinyan Wu
- Department of DermatologyChongzhou People's HospitalChengduChina
| | - Ningwen Zhu
- Department of DermatologyHuashan Hospital, Fudan UniversityShanghaiChina
- Department of PlasticReconstructive and Burns Surgery, Huashan Hospital, Fudan UniversityShanghaiChina
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16
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Jiang Z, Chen L, Huang L, Yu S, Lin J, Li M, Gao Y, Yang L. Bioactive Materials That Promote the Homing of Endogenous Mesenchymal Stem Cells to Improve Wound Healing. Int J Nanomedicine 2024; 19:7751-7773. [PMID: 39099796 PMCID: PMC11297574 DOI: 10.2147/ijn.s455469] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 04/23/2024] [Indexed: 08/06/2024] Open
Abstract
Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.
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Affiliation(s)
- Ziwei Jiang
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Lianglong Chen
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Lei Huang
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Shengxiang Yu
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Jiabao Lin
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Mengyao Li
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Yanbin Gao
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Lei Yang
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
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17
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Chen JG, Zhang EC, Wan YY, Huang TY, Wang YC, Jiang HY. Engineered hsa-miR-455-3p-Abundant Extracellular Vesicles Derived from 3D-Cultured Adipose Mesenchymal Stem Cells for Tissue-Engineering Hyaline Cartilage Regeneration. Adv Healthc Mater 2024; 13:e2304194. [PMID: 38508211 DOI: 10.1002/adhm.202304194] [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: 11/28/2023] [Revised: 03/04/2024] [Indexed: 03/22/2024]
Abstract
Efforts are made to enhance the inherent potential of extracellular vesicles (EVs) by utilizing 3D culture platforms and engineered strategies for functional cargo-loading. Three distinct types of adipose mesenchymal stem cells-derived EVs (ADSCs-EVs) are successfully isolated utilizing 3D culture platforms consisting of porous gelatin methacryloyl (PG), PG combined with sericin methacryloyl (PG/SerMA), or PG combined with chondroitin sulfate methacryloyl (PG/ChSMA). These correspond to PG-EVs, PG/SerMA-EVs, and PG/ChSMA-EVs, respectively. Unique microRNA (miRNA) profiles are observed in each type of ADSCs-EVs. Notably, PG-EVs encapsulate higher levels of hsa-miR-455-3p and deliver more hsa-miR-455-3p to chondrocytes, which results in the activation of the hsa-miR-455-3p/PAK2/Smad2/3 axis and the subsequent hyaline cartilage regeneration. Furthermore, the functionality of PG-EVs is optimized through engineered strategies, including agomir/lentivirus transfection, electroporation, and Exo-Fect transfection. These strategies, referred to as Agomir-EVs, Lentivirus-EVs, Electroporation-EVs, and Exo-Fect-EVs, respectively, are ranked based on their efficacy in encapsulating hsa-miR-455-3p, delivering hsa-miR-455-3p to chondrocytes, and promoting cartilage formation via the hsa-miR-455-3p/PAK2/Smad2/3 axis. Notably, Exo-Fect-EVs exhibit the highest efficiency. Collectively, the 3D culture conditions and engineered strategies have an impact on the miRNA profiles and cartilage regeneration capabilities of ADSCs-EVs. The findings provide valuable insights into the mechanisms underlying the promotion of cartilage regeneration by ADSCs-EVs.
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Affiliation(s)
- Jian-Guo Chen
- Chinese Academy of Medical Sciences and Peking Union Medical College Plastic Surgery Hospital and Institute, Shijingshan District, Beijing, 100144, China
| | - En-Chong Zhang
- Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, China
| | - Ying-Ying Wan
- Beijing University of Chinese Medicine, DongFang Hospital, Fengtai District, Beijing, 100078, China
| | - Tian-Yu Huang
- Chinese Academy of Medical Sciences and Peking Union Medical College Plastic Surgery Hospital and Institute, Shijingshan District, Beijing, 100144, China
| | - Yu-Chen Wang
- Chinese Academy of Medical Sciences and Peking Union Medical College Plastic Surgery Hospital and Institute, Shijingshan District, Beijing, 100144, China
| | - Hai-Yue Jiang
- Chinese Academy of Medical Sciences and Peking Union Medical College Plastic Surgery Hospital and Institute, Shijingshan District, Beijing, 100144, China
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18
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Liu X, Xiong J, Li X, Pan H, Osama H. Meta-analysis study of small extracellular vesicle nursing application therapies for healing of wounds and skin regeneration. Arch Dermatol Res 2024; 316:346. [PMID: 38849563 DOI: 10.1007/s00403-024-02992-4] [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: 04/13/2024] [Revised: 04/14/2024] [Accepted: 04/26/2024] [Indexed: 06/09/2024]
Abstract
We designed and performed this meta-analysis to investigate the impact of the application of extracellular small vesicle therapies on regeneration of skin and wound healing. The findings of this study were computed using fixed or random effect models. The mean differences (MDs), and odds ratio (ORs) with their 95% confidence intervals (CIs) were calculated. In this study, 43 publications were included, encompassing 530 animals with artificial wounds. Small extracellular vesicle therapy had a significant greater rate of wound closure (MD, 24.0; 95% CI, 19.98-28.02, P < 0.001), lower scar width (MD, -191.33; 95%CI, -292.26--90.4, P < 0.001), and higher blood vessel density (MD,36.11; 95%CI, 19.02-53.20, P < 0.001) compared to placebo. Our data revealed that small extracellular vesicle therapy had a significantly higher regeneration of skin and healing of wounds based on the results of wound closure rate, lower scar width, and higher blood vessel density compared to placebo. Future studies with larger sample size are needed.
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Affiliation(s)
- Xianping Liu
- Department of NeuroSurgery, The Affiliated Chengdu 363Hospital of Southwest Medical University, No.550, Campus Road, Pi Du District, Chengdu, 611730, Sichuan, China
| | - Jianping Xiong
- Department of NeuroSurgery, The Affiliated Chengdu 363Hospital of Southwest Medical University, No.550, Campus Road, Pi Du District, Chengdu, 611730, Sichuan, China
| | - Xia Li
- Department of NeuroSurgery, The Affiliated Chengdu 363Hospital of Southwest Medical University, No.550, Campus Road, Pi Du District, Chengdu, 611730, Sichuan, China
| | - Haipeng Pan
- Department of NeuroSurgery, The Affiliated Chengdu 363Hospital of Southwest Medical University, No.550, Campus Road, Pi Du District, Chengdu, 611730, Sichuan, China
| | - Hasnaa Osama
- Department of Clinical Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
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19
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Wu H, Yao Z, Li H, Zhang L, Zhao Y, Li Y, Wu Y, Zhang Z, Xie J, Ding F, Zhu H. Improving dermal fibroblast-to-epidermis communications and aging wound repair through extracellular vesicle-mediated delivery of Gstm2 mRNA. J Nanobiotechnology 2024; 22:307. [PMID: 38825668 PMCID: PMC11145791 DOI: 10.1186/s12951-024-02541-1] [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: 10/21/2023] [Accepted: 05/09/2024] [Indexed: 06/04/2024] Open
Abstract
Skin aging is characterized by the disruption of skin homeostasis and impaired skin injury repair. Treatment of aging skin has long been limited by the unclear intervention targets and delivery techniques. Engineering extracellular vesicles (EVs) as an upgraded version of natural EVs holds great potential in regenerative medicine. In this study, we found that the expression of the critical antioxidant and detoxification gene Gstm2 was significantly reduced in aging skin. Thus, we constructed the skin primary fibroblasts-derived EVs encapsulating Gstm2 mRNA (EVsGstm2), and found that EVsGstm2 could significantly improve skin homeostasis and accelerate wound healing in aged mice. Mechanistically, we found that EVsGstm2 alleviated oxidative stress damage of aging dermal fibroblasts by modulating mitochondrial oxidative phosphorylation, and promoted dermal fibroblasts to regulate skin epidermal cell function by paracrine secretion of Nascent Polypeptide-Associated Complex Alpha subunit (NACA). Furthermore, we confirmed that NACA is a novel skin epidermal cell protective molecule that regulates skin epidermal cell turnover through the ROS-ERK-ETS-Cyclin D pathway. Our findings demonstrate the feasibility and efficacy of EVs-mediated delivery of Gstm2 for aged skin treatment and unveil novel roles of GSTM2 and NACA for improving aging skin.
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Affiliation(s)
- Haiyan Wu
- Institute for Regenerative Medicine & Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
| | - Zuochao Yao
- Department of Plastic and Reconstructive Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
| | - Hongkun Li
- Department of Cardiology, Changzhi Medical College Affiliated Heji Hospital, Shanxi, 046000, China
| | - Laihai Zhang
- Department of Cardiothoracic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Yuying Zhao
- Institute for Regenerative Medicine & Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
| | - Yongwei Li
- Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Yating Wu
- Institute for Regenerative Medicine & Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
| | - Zhenchun Zhang
- Institute for Regenerative Medicine & Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
| | - Jiali Xie
- Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Feixue Ding
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People Hospital, School of Medicine, JiaoTong University, Shanghai, 200001, China
| | - Hongming Zhu
- Institute for Regenerative Medicine & Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
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20
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Baruah H, Sarma A, Basak D, Das M. Exosome: From biology to drug delivery. Drug Deliv Transl Res 2024; 14:1480-1516. [PMID: 38252268 DOI: 10.1007/s13346-024-01515-y] [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] [Accepted: 12/27/2023] [Indexed: 01/23/2024]
Abstract
In recent years, different advancements have been observed in nanosized drug delivery systems. Factors such as stability, safety and targeting efficiency cause hindrances in the clinical translation of these synthetic nanocarriers. Therefore, researchers employed endogenous nanocarriers like exosomes as drug delivery vehicles that have an inherent ability to target more efficiently after appropriate functionalization and show higher biocompatibility and less immunogenicity and facilitate penetration through the biological barriers more quickly than the other available carriers. Exosomes are biologically derived lipid bilayer-enclosed nanosized extracellular vesicles (size ranges from 30 to 150 nm) secreted from both prokaryotic and eukaryotic cells and appears significantly in the extracellular space. These EVs (extracellular vesicles) can exist in different sources, including mammals, plants and microorganisms. Different advanced techniques have been introduced for the isolation of exosomes to overcome the existing barriers present with conventional methods. Extensive research on the application of exosomes in therapeutic delivery for treating various diseases related to central nervous system, bone, cancer, skin, etc. has been employed. Several studies are on different stages of clinical trials, and many exosomes patents have been registered.
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Affiliation(s)
- Himakshi Baruah
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India
| | - Anupam Sarma
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India.
| | - Debojeet Basak
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India
| | - Mridusmita Das
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India
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21
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Xu C, Cao JF, Pei Y, Kim Y, Moon H, Fan CQ, Liao MC, Wang XY, Yao F, Zhang YJ, Zhang SH, Zhang J, Li JZ, Kim JS, Ma L, Xie ZJ. Injectable hydrogel harnessing foreskin mesenchymal stem cell-derived extracellular vesicles for treatment of chronic diabetic skin wounds. J Control Release 2024; 370:339-353. [PMID: 38685383 DOI: 10.1016/j.jconrel.2024.04.049] [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: 11/14/2023] [Revised: 04/22/2024] [Accepted: 04/26/2024] [Indexed: 05/02/2024]
Abstract
Chronic skin wounds are a serious complication of diabetes with a high incidence rate, which can lead to disability or even death. Previous studies have shown that mesenchymal stem cells derived extracellular vesicles (EVs) have beneficial effects on wound healing. However, the human foreskin mesenchymal stem cell (FSMSCs)-derived extracellular vesicle (FM-EV) has not yet been isolated and characterized. Furthermore, the limited supply and short lifespan of EVs also hinder their practical use. In this study, we developed an injectable dual-physical cross-linking hydrogel (PSiW) with self-healing, adhesive, and antibacterial properties, using polyvinylpyrrolidone and silicotungstic acid to load FM-EV. The EVs were evenly distributed in the hydrogel and continuously released. In vivo and vitro tests demonstrated that the synergistic effect of EVs and hydrogel could significantly promote the repair of diabetic wounds by regulating macrophage polarization, promoting angiogenesis, and improving the microenvironment. Overall, the obtained EVs-loaded hydrogels developed in this work exhibited promising applicability for the repair of chronic skin wounds in diabetes patients.
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Affiliation(s)
- Chang Xu
- Institute of Pediatrics, Shenzhen Children's Hospital, Clinical Medical College of Southern University of Science and Technology, Shenzhen 518038, China
| | - Jin-Feng Cao
- Beijing Key Laboratory of Wood Science and Engineering, Beijing Forestry University, Beijing 100083, China; Key Laboratory of Wood Material Science and Application (Beijing Forestry University), Ministry of Education, Beijing 100083, China
| | - Yue Pei
- Institute of Pediatrics, Shenzhen Children's Hospital, Clinical Medical College of Southern University of Science and Technology, Shenzhen 518038, China
| | - Yujin Kim
- Department of Chemistry, Korea University, Seoul 02841, Republic of Korea
| | - Huiyeon Moon
- Department of Chemistry, Korea University, Seoul 02841, Republic of Korea
| | - Chui-Qin Fan
- Institute of Pediatrics, Shenzhen Children's Hospital, Clinical Medical College of Southern University of Science and Technology, Shenzhen 518038, China
| | - Mao-Chuan Liao
- Institute of Pediatrics, Shenzhen Children's Hospital, Clinical Medical College of Southern University of Science and Technology, Shenzhen 518038, China
| | - Xing-Yu Wang
- Department of Emergency, ChangYang Tujia Autonomous County People's Hospital, Yichang 443000, China
| | - Fei Yao
- Eye Center of Xiangya Hospital, Central South University, Changsha 410000, China
| | - Yu-Jun Zhang
- Institute of Pediatrics, Shenzhen Children's Hospital, Clinical Medical College of Southern University of Science and Technology, Shenzhen 518038, China
| | - Shao-Hui Zhang
- Institute of Materials Science and Devices, School of Materials Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China
| | - Jian Zhang
- Institute of Materials Science and Devices, School of Materials Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China
| | - Jian-Zhang Li
- Beijing Key Laboratory of Wood Science and Engineering, Beijing Forestry University, Beijing 100083, China; Key Laboratory of Wood Material Science and Application (Beijing Forestry University), Ministry of Education, Beijing 100083, China.
| | - Jong Seung Kim
- Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.
| | - Lian Ma
- Institute of Pediatrics, Shenzhen Children's Hospital, Clinical Medical College of Southern University of Science and Technology, Shenzhen 518038, China; Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen 518038, China; Department of Pediatrics, The Third Affifiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
| | - Zhong-Jian Xie
- Institute of Pediatrics, Shenzhen Children's Hospital, Clinical Medical College of Southern University of Science and Technology, Shenzhen 518038, China; Shenzhen International Institute for Biomedical Research, Shenzhen 518116, Guangdong, China.
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22
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Kumar M, Mahmood S, Chopra S, Bhatia A. Biopolymer based nanoparticles and their therapeutic potential in wound healing - A review. Int J Biol Macromol 2024; 267:131335. [PMID: 38604431 DOI: 10.1016/j.ijbiomac.2024.131335] [Citation(s) in RCA: 27] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 03/11/2024] [Accepted: 04/01/2024] [Indexed: 04/13/2024]
Abstract
Nanoparticles (NPs) have been extensively investigated for their potential in nanomedicine. There is a significant level of enthusiasm about the potential of NPs to bring out a transformative impact on modern healthcare. NPs can serve as effective wound dressings or delivery vehicles due to their antibacterial and pro-wound-healing properties. Biopolymer-based NPs can be manufactured using various food-grade biopolymers, such as proteins, polysaccharides, and synthetic polymers, each offering distinct properties suitable for different applications which include collagen, polycaprolactone, chitosan, alginate, and polylactic acid, etc. Their biodegradable and biocompatible nature renders them ideal nanomaterials for applications in wound healing. Additionally, the nanofibers containing biopolymer-based NPs have shown excellent anti-bacterial and wound healing activity like silver NPs. These NPs represent a paradigm shift in wound healing therapies, offering targeted and personalized solutions for enhanced tissue regeneration and accelerated wound closure. The current review focuses on biopolymer NPs with their applications in wound healing.
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Affiliation(s)
- Mohit Kumar
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda 151001, Punjab, India
| | - Syed Mahmood
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Shruti Chopra
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda 151001, Punjab, India.
| | - Amit Bhatia
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda 151001, Punjab, India.
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23
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Shang S, Zhuang K, Chen J, Zhang M, Jiang S, Li W. A bioactive composite hydrogel dressing that promotes healing of both acute and chronic diabetic skin wounds. Bioact Mater 2024; 34:298-310. [PMID: 38261910 PMCID: PMC10796815 DOI: 10.1016/j.bioactmat.2023.12.026] [Citation(s) in RCA: 26] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/28/2023] [Accepted: 12/29/2023] [Indexed: 01/25/2024] Open
Abstract
Mesenchymal stem cell derived exosomes (MSC-Exos) demonstrate beneficial effects on wound healing via anti-inflammatory and angiogenic properties. Chitosan (CS) exhibits excellent biocompatibility and accelerates cellular migration, adhesion, and proliferation. The ions released from bioactive glass (BG) and titanium dioxide (TiO2) nanoparticles exhibit sustained angiogenic and antibacterial potency. In this study, CMCS-CEBT hydrogel was synthesized from exosomes encapsulated carboxymethyl chitosan (CMCS), chitosan nanoparticles (CS-NPs), BG, and TiO2 nanoparticles for a preliminary evaluation of its impacts on the treatment of full-thickness skin defects, diabetic wounds, and burn skin injury due to burns. In vitro analysis indicated that the hydrogel exhibits excellent cell compatibility, stimulates endothelial cell adhesion and proliferation, and presents anti-inflammatory, angiogenic, and antibacterial activities. In vivo, the composite hydrogel dressing accelerated a wound healing acceleration effect, stimulated angiogenesis, and increased collagen deposition and the expression of anti-inflammatory factors. This innovative composite hydrogel dressing as a potential clinical therapy, utilizing bioactive materials, holds promise as a potential clinical therapy that aims to facilitate the regeneration of acute and chronically damaged skin tissue.
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Affiliation(s)
- Shunlai Shang
- Department of Nephrology, China-Japan Friendship Hospital, Beijing, China
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China
| | - Kaiting Zhuang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China
| | - Jianwen Chen
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China
| | - Ming Zhang
- Department of Nephrology, Affiliated Beijing Chaoyang Hospital of Capital Medical University, Beijing, 100020, China
| | - Shimin Jiang
- Department of Nephrology, China-Japan Friendship Hospital, Beijing, China
| | - Wenge Li
- Department of Nephrology, China-Japan Friendship Hospital, Beijing, China
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24
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Li X, Zhang D, Yu Y, Wang L, Zhao M. Umbilical cord-derived mesenchymal stem cell secretome promotes skin regeneration and rejuvenation: From mechanism to therapeutics. Cell Prolif 2024; 57:e13586. [PMID: 38148579 PMCID: PMC10984109 DOI: 10.1111/cpr.13586] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 10/31/2023] [Accepted: 11/22/2023] [Indexed: 12/28/2023] Open
Abstract
How to effectively repair cutaneous wounds and promote skin rejuvenation has always been a challenging issue for clinical medicine and medical aesthetics. Current conventional medicines exhibit several drawbacks, including limited therapeutic effects, prolonged treatment periods, and high costs. As a novel cell-free therapy, the umbilical cord-derived mesenchymal stem cell (UCMSC) secretome may offer a promising approach for skin regeneration and rejuvenation. The UCMSC secretome is a collection of all proteins secreted by mesenchymal stem cells, including conditioned media, exosomes, and other substances. The UCMSC secretome has numerous abilities to accelerate acute wound healing, including high fibroblast and keratinocyte proliferative activity, pro-angiogenesis, anti-inflammation, anti-fibrosis, and anti-oxidative stress. Its impact on the four stages of wound healing is manifested by inducing the haemostasis phase, inhibiting the inflammation phase, promoting the proliferation phase, and regulating the remodelling phase. Furthermore, it is highly effective in the treatment of chronic wounds, alopecia, aging, and skin homeostasis disturbance. This review focuses on the clinical therapies and application prospects of the UCMSC secretome, encompassing its source, culture, separation, identification, storage, and pretreatment. Additionally, a discussion on the dosage, administration route, efficacy, and biosafety in the clinical situation is presented. This review aims to provide scientific support for the mechanistic investigation and clinical utilisation of the UCMSC secretome in wound healing and skin rejuvenation.
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Affiliation(s)
- Xixian Li
- Department of Plastic SurgeryThe Second Hospital of Dalian Medical UniversityDalianLiaoningChina
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical Physics, Chinese Academy of SciencesDalianLiaoningChina
| | - Dan Zhang
- Department of Plastic SurgeryThe Second Hospital of Dalian Medical UniversityDalianLiaoningChina
| | - Yang Yu
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical Physics, Chinese Academy of SciencesDalianLiaoningChina
| | - Liang Wang
- Research and Teaching Department of Comparative MedicineDalian Medical UniversityDalianLiaoningChina
| | - Muxin Zhao
- Department of Plastic SurgeryThe Second Hospital of Dalian Medical UniversityDalianLiaoningChina
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25
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Song Y, Wu J, Liu Y, Xu N, Bai H, Wang L, Ai J, Li K. The remodeling of ovarian function: targeted delivery strategies for mesenchymal stem cells and their derived extracellular vesicles. Stem Cell Res Ther 2024; 15:90. [PMID: 38539206 PMCID: PMC10976842 DOI: 10.1186/s13287-024-03704-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 03/19/2024] [Indexed: 06/13/2025] Open
Abstract
Premature ovarian insufficiency (POI) is an essential cause of reduced fertility and quality of life in young women. Mesenchymal stem cells (MSCs) and MSCs-derived extracellular vesicles (EVs) have the ability to migrate to damaged tissues and are considered as promising therapeutic approaches for POI. However, the homing ability and therapeutic efficacy of MSCs administered in vivo are still insufficient, and their potential tumorigenicity and multi-differentiation potential also bring many doubts about their safety. The targeting ability and migration efficiency of MSCs can be improved by genetic engineering and surface modification, thereby maximizing their therapeutic efficacy. However, the use of viral vectors also has increased safety concerns. In addition, EVs, which seem to be the current therapeutic alternative to MSCs, are still poorly targeted for distribution, although they have improved in terms of safety. This paper reviews the comparative therapeutic effects of MSCs and their derived EVs on POI, their biodistribution after in vivo administration, and the most important possible ovarian targeting strategies. Difficulties such as homogeneity and yield before clinical application are also discussed. This article will provide new insights into precision therapy and targeted drug delivery for female ovarian diseases.
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Affiliation(s)
- Yinhua Song
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Jiachen Wu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Yang Liu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Na Xu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Hualin Bai
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Lingjuan Wang
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
| | - Jihui Ai
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
| | - Kezhen Li
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
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26
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Zhu D, Hu Y, Kong X, Luo Y, Zhang Y, Wu Y, Tan J, Chen J, Xu T, Zhu L. Enhanced burn wound healing by controlled-release 3D ADMSC-derived exosome-loaded hyaluronan hydrogel. Regen Biomater 2024; 11:rbae035. [PMID: 38628545 PMCID: PMC11018541 DOI: 10.1093/rb/rbae035] [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: 10/29/2023] [Revised: 02/23/2024] [Accepted: 03/17/2024] [Indexed: 04/19/2024] Open
Abstract
Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.
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Affiliation(s)
- Delong Zhu
- Department of Dermatology & Plastic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Ying Hu
- Department of Dermatology & Plastic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Xiangkai Kong
- Department of Dermatology & Plastic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Yuansen Luo
- Department of the Second Plastic Surgery, The First People’s Hospital of Foshan, Foshan 528000, China
| | - Yi Zhang
- Department of Research and Development, Huaqing Zhimei (Shenzhen) Biotechnology Co., Ltd, Shenzhen 518107, People’s Republic of China
| | - Yu Wu
- Department of Dermatology & Plastic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Jiameng Tan
- Department of Dermatology & Plastic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Jianwei Chen
- Center for Bio-Intelligent Manufacturing and Living Matter Bioprinting, Research Institute of Tsinghua University in Shenzhen, Tsinghua University, Shenzhen 518057, People’s Republic of China
| | - Tao Xu
- Center for Bio-Intelligent Manufacturing and Living Matter Bioprinting, Research Institute of Tsinghua University in Shenzhen, Tsinghua University, Shenzhen 518057, People’s Republic of China
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, People’s Republic of China
| | - Lei Zhu
- Department of Dermatology & Plastic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
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27
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Zhang H, Mao Y, Nie Z, Li Q, Wang M, Cai C, Hao W, Shen X, Gu N, Shen W, Song H. Iron Oxide Nanoparticles Engineered Macrophage-Derived Exosomes for Targeted Pathological Angiogenesis Therapy. ACS NANO 2024; 18:7644-7655. [PMID: 38412252 PMCID: PMC10938920 DOI: 10.1021/acsnano.4c00699] [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] [Received: 01/16/2024] [Revised: 02/16/2024] [Accepted: 02/23/2024] [Indexed: 02/29/2024]
Abstract
Engineering exosomes with nanomaterials usually leads to the damage of exosomal membrane and bioactive molecules. Here, pathological angiogenesis targeting exosomes with magnetic imaging, ferroptosis inducing, and immunotherapeutic properties is fabricated using a simple coincubation method with macrophages being the bioreactor. Extremely small iron oxide nanoparticle (ESIONPs) incorporated exosomes (ESIONPs@EXO) are acquired by sorting the secreted exosomes from M1-polarized macrophages induced by ESIONPs. ESIONPs@EXO suppress pathological angiogenesis in vitro and in vivo without toxicity. Furthermore, ESIONPs@EXO target pathological angiogenesis and exhibit an excellent T1-weighted contrast property for magnetic resonance imaging. Mechanistically, ESIONPs@EXO induce ferroptosis and exhibit immunotherapeutic ability toward pathological angiogenesis. These findings demonstrate that a pure biological method engineered ESIONPs@EXO using macrophages shows potential for targeted pathological angiogenesis therapy.
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Affiliation(s)
- Haorui Zhang
- Department
of Ophthalmology, Shanghai Changhai Hospital, Shanghai 200433, P.R. China
| | - Yu Mao
- Nanjing
Key Laboratory for Cardiovascular Information and Health Engineering
Medicine, Institute of Clinical Medicine, Nanjing Drum Tower Hospital,
Medical School, Nanjing University, Nanjing 210093, P.R. China
| | - Zheng Nie
- Department
of Ophthalmology, Shanghai Changhai Hospital, Shanghai 200433, P.R. China
| | - Qing Li
- Department
of Ophthalmology, Shanghai Changhai Hospital, Shanghai 200433, P.R. China
| | - Mengzhu Wang
- Department
of Ophthalmology, Shanghai Changhai Hospital, Shanghai 200433, P.R. China
| | - Chang Cai
- Department
of Ophthalmology, Shanghai Changhai Hospital, Shanghai 200433, P.R. China
| | - Weiju Hao
- University
of Shanghai for Science and Technology, Shanghai 200093, P.R. China
| | - Xi Shen
- Department
of Ophthalmology, Ruijin Hospital, Shanghai
Jiao Tong University School of Medicine, Shanghai 200020, P.R. China
| | - Ning Gu
- Nanjing
Key Laboratory for Cardiovascular Information and Health Engineering
Medicine, Institute of Clinical Medicine, Nanjing Drum Tower Hospital,
Medical School, Nanjing University, Nanjing 210093, P.R. China
| | - Wei Shen
- Department
of Ophthalmology, Shanghai Changhai Hospital, Shanghai 200433, P.R. China
| | - Hongyuan Song
- Department
of Ophthalmology, Shanghai Changhai Hospital, Shanghai 200433, P.R. China
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28
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Liao Y, Zhang Z, Ouyang L, Mi B, Liu G. Engineered Extracellular Vesicles in Wound Healing: Design, Paradigms, and Clinical Application. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2307058. [PMID: 37806763 DOI: 10.1002/smll.202307058] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 09/20/2023] [Indexed: 10/10/2023]
Abstract
The severe quality of life and economic burden imposed by non-healing skin wounds, infection risks, and treatment costs are affecting millions of patients worldwide. To mitigate these challenges, scientists are relentlessly seeking effective treatment measures. In recent years, extracellular vesicles (EVs) have emerged as a promising cell-free therapy strategy, attracting extensive attention from researchers. EVs mediate intercellular communication, possessing excellent biocompatibility and stability. These features make EVs a potential tool for treating a plethora of diseases, including those related to wound repair. However, there is a growing focus on the engineering of EVs to overcome inherent limitations such as low production, relatively fixed content, and targeting capabilities of natural EVs. This engineering could improve both the effectiveness and specificity of EVs in wound repair treatments. In light of this, the present review will introduce the latest progress in the design methods and experimental paradigms of engineered EVs applied in wound repair. Furthermore, it will comprehensively analyze the current clinical research status and prospects of engineered EVs within this field.
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Affiliation(s)
- Yuheng Liao
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Zhenhe Zhang
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Lizhi Ouyang
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Bobin Mi
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Guohui Liu
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
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29
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Jang HJ, Shim KS, Lee J, Park JH, Kang SJ, Shin YM, Lee JB, Baek W, Yoon JK. Engineering of Cell Derived-Nanovesicle as an Alternative to Exosome Therapy. Tissue Eng Regen Med 2024; 21:1-19. [PMID: 38066355 PMCID: PMC10764700 DOI: 10.1007/s13770-023-00610-4] [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: 10/04/2023] [Revised: 10/24/2023] [Accepted: 10/27/2023] [Indexed: 01/04/2024] Open
Abstract
BACKGROUND Exosomes, nano-sized vesicles ranging between 30 and 150 nm secreted by human cells, play a pivotal role in long-range intercellular communication and have attracted significant attention in the field of regenerative medicine. Nevertheless, their limited productivity and cost-effectiveness pose challenges for clinical applications. These issues have recently been addressed by cell-derived nanovesicles (CDNs), which are physically synthesized exosome-mimetic nanovesicles from parent cells, as a promising alternative to exosomes. CDNs exhibit structural, physical, and biological properties similar to exosomes, containing intracellular protein and genetic components encapsulated by the cell plasma membrane. These characteristics allow CDNs to be used as regenerative medicine and therapeutics on their own, or as a drug delivery system. METHODS The paper reviews diverse methods for CDN synthesis, current analysis techniques, and presents engineering strategies to improve lesion targeting efficiency and/or therapeutic efficacy. RESULTS CDNs, with their properties similar to those of exosomes, offer a cost-effective and highly productive alternative due to their non-living biomaterial nature, nano-size, and readiness for use, allowing them to overcome several limitations of conventional cell therapy methods. CONCLUSION Ongoing research and enhancement of CDNs engineering, along with comprehensive safety assessments and stability analysis, exhibit vast potential to advance regenerative medicine by enabling the development of efficient therapeutic interventions.
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Affiliation(s)
- Hye-Jeong Jang
- Department of Systems Biotechnology, Chung-Ang University, Anseong-Si, Gyeonggi-Do, 17546, Republic of Korea
| | - Kyu-Sik Shim
- Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
| | - Jinah Lee
- Department of Biological Science, Research Institute of Women's Health, Brain Korea 21 Project, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - Joo Hyeon Park
- Department of Biological Science, Research Institute of Women's Health, Brain Korea 21 Project, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - Seong-Jun Kang
- Department of Systems Biotechnology, Chung-Ang University, Anseong-Si, Gyeonggi-Do, 17546, Republic of Korea
| | - Young Min Shin
- Department of Biological Science, Research Institute of Women's Health, Brain Korea 21 Project, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - Jung Bok Lee
- Department of Biological Science, Research Institute of Women's Health, Brain Korea 21 Project, Sookmyung Women's University, Seoul, 04310, Republic of Korea.
| | - Wooyeol Baek
- Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
| | - Jeong-Kee Yoon
- Department of Systems Biotechnology, Chung-Ang University, Anseong-Si, Gyeonggi-Do, 17546, Republic of Korea.
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30
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Guo P, Wang Q, Chen L, Dingya K, Wang B. Ultrasound-Responsive Micelle-Encapsulated Mesenchymal Stem Cell-Derived EVs for the Treatment of Lower Limb Microcirculation Disease. ACS OMEGA 2023; 8:49406-49419. [PMID: 38162755 PMCID: PMC10753545 DOI: 10.1021/acsomega.3c08133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/25/2023] [Accepted: 11/27/2023] [Indexed: 01/03/2024]
Abstract
Lower limb microcirculatory ischemic disease is a vascular disorder primarily characterized by limb pain, gangrene, and potential amputation. It can be caused by various factors, such as hyperglycemia, atherosclerosis, and infection. Due to the extremely narrow luminal diameter in lower limb microcirculatory ischemic lesions, both surgical and medical interventions face challenges in achieving satisfactory therapeutic outcomes within the microvessels. Extracellular vesicles derived from mesenchymal stem cells (MSCs-EVs) exhibit promising potential in the treatment of microcirculation ischemic lesions due to their small size and ability to promote angiogenesis. After undergoing substantial losses during the process of EVs transportation, only a minimal fraction of EVs can effectively reach the site of microcirculatory lesions, thereby compromising the therapeutic efficacy for microcirculatory disorders. Herein, an ultrasound-responsive system utilizing 2-(dimethylamino)ethyl methacrylate-b-2-tetrahydropyranyl methacrylate (DMAEMA-b-THPMA) micelles to encapsulate MSCs-EVs has been successfully constructed, with the aim of achieving localized and targeted release of EVs at the site of microcirculatory lesions. The reversible addition-fragmentation chain transfer (RAFT) polymerization method facilitates the successful synthesis of diblock copolymers comprising monomer 2-(dimethylamino)ethyl methacrylate (DMAEMA) and monomer 2-tetrahydropyranyl methacrylate (THPMA). The DMAEMA-b-THPMA micelles exhibit a nanoscale structure, reliable biocompatibility, ultrasound responsiveness, and conspicuous protection of EVs. Furthermore, the implementation of low-energy-density ultrasound can enhance angiogenesis by upregulating the levels of the vascular endothelial growth factor (VEGF). In in vivo experiments, the ultrasound-responsive system of the DMAEMA-b-THPMA micelles and MSCs-EVs synergistically enhances therapeutic efficacy by promoting angiogenesis, improving vascular permeability, and optimizing vascular. In conclusion, this work demonstrates bioapplication of an ultrasound-responsive micellar nanosystem loaded with EVs for the treatment of lower limb microcirculatory ischemic disorders.
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Affiliation(s)
- Peng Guo
- The
Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Qian Wang
- College
of Materials and Chemical Engineering, West
Anhui University, Luan 237012, Anhui, China
| | - Ling Chen
- The
First Affiliated Hospital of Lanzhou University, Lanzhou 730000, Gansu, China
| | - Kun Dingya
- The
Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Bing Wang
- The
Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, Henan, China
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31
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Ren J, Jing X, Liu Y, Liu J, Ning X, Zong M, Zhang R, Cheng H, Cui J, Li B, Wu X. Exosome-based engineering strategies for the diagnosis and treatment of oral and maxillofacial diseases. J Nanobiotechnology 2023; 21:501. [PMID: 38129853 PMCID: PMC10740249 DOI: 10.1186/s12951-023-02277-4] [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: 10/16/2023] [Accepted: 12/15/2023] [Indexed: 12/23/2023] Open
Abstract
Oral and maxillofacial diseases are one of the most prevalent diseases in the world, which not only seriously affect the health of patients' oral and maxillofacial tissues, but also bring serious economic and psychological burdens to patients. Therefore, oral and maxillofacial diseases require effective treatment. Traditional treatments have limited effects. In recent years, nature exosomes have attracted increasing attention due to their ability to diagnose and treat diseases. However, the application of nature exosomes is limited due to low yield, high impurities, lack of targeting, and high cost. Engineered exosomes can be endowed with better comprehensive therapeutic properties by modifying exosomes of parent cells or directly modifying exosomes, and biomaterial loading exosomes. Compared with natural exosomes, these engineered exosomes can achieve more effective diagnosis and treatment of oral and maxillary system diseases, and provide reference and guidance for clinical application. This paper reviews the engineering modification methods of exosomes and the application of engineered exosomes in oral and maxillofacial diseases and looks forward to future research directions.
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Affiliation(s)
- Jianing Ren
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Xuan Jing
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Yingyu Liu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Jinrong Liu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Xiao Ning
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Mingrui Zong
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Ran Zhang
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Huaiyi Cheng
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Jiayu Cui
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Bing Li
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China.
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China.
| | - Xiuping Wu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China.
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China.
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Abbasi R, Mesgin RM, Nazari-Khanamiri F, Abdyazdani N, Imani Z, Talatapeh SP, Nourmohammadi A, Nejati V, Rezaie J. Mesenchymal stem cells-derived exosomes: novel carriers for nanoparticle to combat cancer. Eur J Med Res 2023; 28:579. [PMID: 38071346 PMCID: PMC10709841 DOI: 10.1186/s40001-023-01556-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 11/29/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND The advancement in novel cancer therapeutics brought a platform combining the properties of exosomes with nanoparticles to precision medicine. The novel therapeutic approach aim is cancer-targeted therapy. Exosomes from mesenchymal stem cells (MSCs-Exo) exhibit unique properties in cancer therapies, which makes them an ideal tool for delivering therapeutic agents into tumor cells. The key role of natural MSCs-Exo is controversial in cancer therapy; however, they can be engineered at their surface or cargo to serve as a smart drug delivery system for cancer-targeted therapy. In the last few years, researchers harnessed nanotechnology to enforce MSCs-Exo for cancer management including, tumor cell tracking, imaging, and tumor cell killing. Different nanoparticles such as gold nanoparticles have particularly been incorporated into MSCs-Exo, which showed an efficient accumulation at the site of tumor with improved anticancer impact. These findings indicate that a hybrid of exosomes-nanoparticles may serve as combination therapy for the effective removal of cancers. SHORT CONCLUSION Although exhibiting impressive potential, the use of nanoparticle-loaded MSCs-Exo as a drug-delivery tool has been troubled by some challenges, therefore, translation to clinic prerequisites further scrutiny. In this review, we focus on nanoparticle-loaded MSCs-Exo as a new cancer therapy and discuss engineered MSC-Exo for target therapy.
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Affiliation(s)
- Reza Abbasi
- Department of Biology, Urmia University, Urmia, Iran
| | | | - Fereshteh Nazari-Khanamiri
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Shafa St, Ershad Blvd, Urmia, Iran
| | - Nima Abdyazdani
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zeynab Imani
- Department of Biology, Urmia University, Urmia, Iran
| | | | - Aidin Nourmohammadi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vahid Nejati
- Department of Biology, Urmia University, Urmia, Iran.
| | - Jafar Rezaie
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Shafa St, Ershad Blvd, Urmia, Iran.
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Fan L, Ma X, Liu B, Yang Y, Yang Y, Ren T, Li Y. Antioxidant-Engineered Milk-Derived Extracellular Vesicles for Accelerating Wound Healing via Regulation of the PI3K-AKT Signaling Pathway. Adv Healthc Mater 2023; 12:e2301865. [PMID: 37660257 DOI: 10.1002/adhm.202301865] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 08/17/2023] [Indexed: 09/04/2023]
Abstract
Inspired by the experience of relieving inflammation in infants with milk, antioxidant-engineered milk-derived extracellular vesicles (MEVs) are developed to evaluate their potential for accelerating wound healing. In this work, MEVs with polydopamines (PDA) are engineered using the co-extrusion method. Subsequently, the authors incorporated them into a Schiff-based crosslink hydrogel, forming a skin dosage form that could facilitate the wound healing process. The antioxidant properties of PDA assist in the anti-inflammatory function of engineered MEVs, while the gel provides better skin residency. The PDA@MEVs+GEL formulation exhibits excellent biocompatibility, pro-angiogenic capacity, and antioxidant ability in vitro. Furthermore, in vivo experiments demonstrate its efficacy in wound repair and inflammation inhibition. Mechanistically, PDA@MEVs+GEL simultaneously promotes the growth, migration, and anti-inflammation of 3T3 cells by activating PI3K-AKT pathway. Moreover, PDA@MEVs+GEL exhibits enhanced functionality in promoting wound healing in vivo, attributed to its ability to inhibit inflammation, stimulate angiogenesis, and promote collagen synthesis. In conclusion, this study delves into the mechanism of MEVs and underscores the improved efficacy of engineered extracellular vesicles. Additionally, the feasibility and prospect of engineered MEVs in treating skin wounds are verified, suggesting that antioxidant-engineered MEVs could be a promising therapeutic agent for wound healing applications.
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Affiliation(s)
- Limin Fan
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092, P. R. China
| | - Xiaoyi Ma
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092, P. R. China
| | - Bingbing Liu
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092, P. R. China
| | - Yushan Yang
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092, P. R. China
| | - Yan Yang
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092, P. R. China
| | - Tianbin Ren
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092, P. R. China
| | - Yongyong Li
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092, P. R. China
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34
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Lee CS, Lee M, Na K, Hwang HS. Stem Cell-Derived Extracellular Vesicles for Cancer Therapy and Tissue Engineering Applications. Mol Pharm 2023; 20:5278-5311. [PMID: 37867343 DOI: 10.1021/acs.molpharmaceut.3c00376] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
Recently, stem cells and their secretomes have attracted great attention in biomedical applications, particularly extracellular vesicles (EVs). EVs are secretomes of cells for cell-to-cell communication. They play a role as intercellular messengers as they carry proteins, nucleic acids, lipids, and therapeutic agents. They have also been utilized as drug-delivery vehicles due to their biocompatibility, low immunogenicity, stability, targetability, and engineerable properties. The therapeutic potential of EVs can be further enhanced by surface engineering and modification using functional molecules such as aptamers, peptides, and antibodies. As a consequence, EVs hold great promise as effective delivery vehicles for enhancing treatment efficacy while avoiding side effects. Among various cell types that secrete EVs, stem cells are ideal sources of EVs because stem cells have unique properties such as self-renewal and regenerative potential for transplantation into damaged tissues that can facilitate their regeneration. However, challenges such as immune rejection and ethical considerations remain significant hurdles. Stem cell-derived EVs have been extensively explored as a cell-free approach that bypasses many challenges associated with cell-based therapy in cancer therapy and tissue regeneration. In this review, we summarize and discuss the current knowledge of various types of stem cells as a source of EVs, their engineering, and applications of EVs, focusing on cancer therapy and tissue engineering.
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Affiliation(s)
- Chung-Sung Lee
- Department of Pharmaceutical Engineering, Soonchunhyang University, Asan 31538, Republic of Korea
| | - Min Lee
- Division of Advanced Prosthodontics, University of California, Los Angeles, California 90095, United States
- Department of Bioengineering, University of California, Los Angeles, California 90095, United States
| | - Kun Na
- Department of BioMedical-Chemical Engineering, The Catholic University of Korea, Bucheon 14662, Republic of Korea
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Republic of Korea
| | - Hee Sook Hwang
- Department of Pharmaceutical Engineering, Dankook University, Cheonan 31116, Republic of Korea
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35
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Mehryab F, Taghizadeh F, Goshtasbi N, Merati F, Rabbani S, Haeri A. Exosomes as cutting-edge therapeutics in various biomedical applications: An update on engineering, delivery, and preclinical studies. Biochimie 2023; 213:139-167. [PMID: 37207937 DOI: 10.1016/j.biochi.2023.05.010] [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: 12/24/2022] [Revised: 04/29/2023] [Accepted: 05/16/2023] [Indexed: 05/21/2023]
Abstract
Exosomes are cell-derived nanovesicles, circulating in different body fluids, and acting as an intercellular mechanism. They can be purified from culture media of different cell types and carry an enriched content of various protein and nucleic acid molecules originating from their parental cells. It was indicated that the exosomal cargo can mediate immune responses via many signaling pathways. Over recent years, the therapeutic effects of various exosome types were broadly investigated in many preclinical studies. Herein, we present an update on recent preclinical studies on exosomes as therapeutic and/or delivery agents for various applications. The exosome origin, structural modifications, natural or loaded active ingredients, size, and research outcomes were summarized for various diseases. Overall, the present article provides an overview of the latest exosome research interests and developments to clear the way for the clinical study design and application.
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Affiliation(s)
- Fatemeh Mehryab
- Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Taghizadeh
- Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nazanin Goshtasbi
- Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Faezeh Merati
- Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahram Rabbani
- Research Center for Advanced Technologies in Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Azadeh Haeri
- Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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36
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Daneste H, Mohammadzadeh Boukani L, Ramezani N, Asadi F, Zaidan HK, Sadeghzade A, Ehsannia M, Azarashk A, Gholizadeh N. Combination therapy along with mesenchymal stem cells in wound healing; the state of the art. Adv Med Sci 2023; 68:441-449. [PMID: 37924749 DOI: 10.1016/j.advms.2023.10.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 06/23/2023] [Accepted: 10/17/2023] [Indexed: 11/06/2023]
Abstract
Mesenchymal stem cells (MSCs) are being increasingly used in various therapeutic applications including skin tissue repair and wound healing. The positive effects of the MSCs therapy are largely elicited by immunomodulation, increasing angiogenesis, supporting extracellular matrix (ECM) and thus favoring skin structure. However, the therapeutic competences of MSC-based therapies are somewhat hindered by their apparent modest clinical merits, conferring the need for methods that would rise the efficacy of such therapies. A plethora of reports have shown that therapeutic properties of MSCs could be enhanced with other strategies and compounds like biomaterial and platelet-rich plasma (PRP) to target key possessions of MSCs and properties of adjacent tissues concurrently. Manipulation of cellular stress-response mechanisms to improve cell resistance to oxidative stress prior to or during MSC injection could also improve therapeutic efficacy of MSCs. In the current review, we shed light on the recent advances in MSCs combination therapy with other ingredients and procedures to sustain MSCs-mediated effects in wound healing.
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Affiliation(s)
- Hossein Daneste
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Narges Ramezani
- Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
| | - Fatemeh Asadi
- Department of Genetics, Izeh Branch, Islamic Azad University, Izeh, Iran
| | - Haider Kamil Zaidan
- Department of Medical Laboratories Techniques, Al-Mustaqbal University College, Hillah, Babylon, Iraq
| | - Azita Sadeghzade
- Department of Oral and Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maedeh Ehsannia
- Faculty of Basic Sciences, Islamic Azad University, Tehran East Branch, Tehran, Iran
| | - Ali Azarashk
- Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Nasim Gholizadeh
- Department of Dermatology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
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37
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Ma Y, Brocchini S, Williams GR. Extracellular vesicle-embedded materials. J Control Release 2023; 361:280-296. [PMID: 37536545 DOI: 10.1016/j.jconrel.2023.07.059] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/27/2023] [Accepted: 07/31/2023] [Indexed: 08/05/2023]
Abstract
Extracellular vesicles (EVs) are small membrane-bound vesicles released by cells. EVs are emerging as a promising class of therapeutic entity that could be adapted in formulation due to their lack of immunogenicity and targeting capabilities. EVs have been shown to have similar regenerative and therapeutic effects to their parental cells and also have potential in disease diagnosis. To improve the therapeutic potential of EVs, researchers have developed various strategies for modifying them, including genetic engineering and chemical modifications which have been examined to confer target specificity and prevent rapid clearance after systematic injection. Formulation efforts have focused on utilising hydrogel and nano-formulation strategies to increase the persistence of EV localisation in a specific tissue or organ. Researchers have also used biomaterials or bioscaffolds to deliver EVs directly to disease sites and prolong EV release and exposure. This review provides an in-depth examination of the material design of EV delivery systems, highlighting the impact of the material properties on the molecular interactions and the maintenance of EV stability and function. The various characteristics of materials designed to regulate the stability, release rate and biodistribution of EVs are described. Other aspects of material design, including modification methods to improve the targeting of EVs, are also discussed. This review aims to offer an understanding of the strategies for designing EV delivery systems, and how they can be formulated to make the transition from laboratory research to clinical use.
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Affiliation(s)
- Yingchang Ma
- UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London WC1N 1AX, UK
| | - Steve Brocchini
- UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London WC1N 1AX, UK
| | - Gareth R Williams
- UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London WC1N 1AX, UK.
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38
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Danilushkina AA, Emene CC, Barlev NA, Gomzikova MO. Strategies for Engineering of Extracellular Vesicles. Int J Mol Sci 2023; 24:13247. [PMID: 37686050 PMCID: PMC10488046 DOI: 10.3390/ijms241713247] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/14/2023] [Accepted: 08/17/2023] [Indexed: 09/10/2023] Open
Abstract
Extracellular vesicles (EVs) are membrane vesicles released by cells into the extracellular space. EVs mediate cell-to-cell communication through local and systemic transportation of biomolecules such as DNA, RNA, transcription factors, cytokines, chemokines, enzymes, lipids, and organelles within the human body. EVs gained a particular interest from cancer biology scientists because of their role in the modulation of the tumor microenvironment through delivering bioactive molecules. In this respect, EVs represent an attractive therapeutic target and a means for drug delivery. The advantages of EVs include their biocompatibility, small size, and low immunogenicity. However, there are several limitations that restrict the widespread use of EVs in therapy, namely, their low specificity and payload capacity. Thus, in order to enhance the therapeutic efficacy and delivery specificity, the surface and composition of extracellular vesicles should be modified accordingly. In this review, we describe various approaches to engineering EVs, and further discuss their advantages and disadvantages to promote the application of EVs in clinical practice.
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Affiliation(s)
- Anna A. Danilushkina
- Laboratory of Intercellular Communications, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420021 Kazan, Russia
| | - Charles C. Emene
- Laboratory of Intercellular Communications, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420021 Kazan, Russia
| | - Nicolai A. Barlev
- Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
- Department of Biomedicine, Nazarbayev University School of Medicine, Astana 001000, Kazakhstan
| | - Marina O. Gomzikova
- Laboratory of Intercellular Communications, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420021 Kazan, Russia
- Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
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39
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Ding JY, Chen MJ, Wu LF, Shu GF, Fang SJ, Li ZY, Chu XR, Li XK, Wang ZG, Ji JS. Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges. Mil Med Res 2023; 10:36. [PMID: 37587531 PMCID: PMC10433599 DOI: 10.1186/s40779-023-00472-w] [Citation(s) in RCA: 55] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 07/24/2023] [Indexed: 08/18/2023] Open
Abstract
Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EVs-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks.
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Affiliation(s)
- Jia-Yi Ding
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Institute of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Zhejiang, 323000, Lishui, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China
| | - Min-Jiang Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Institute of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Zhejiang, 323000, Lishui, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China
| | - Ling-Feng Wu
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China
- Clinical College of the Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, Zhejiang, China
| | - Gao-Feng Shu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Institute of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Zhejiang, 323000, Lishui, China
- Clinical College of the Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, Zhejiang, China
| | - Shi-Ji Fang
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Institute of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Zhejiang, 323000, Lishui, China
- Clinical College of the Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, Zhejiang, China
| | - Zhao-Yu Li
- Department of Overseas Education College, Jimei University, Xiamen, 361021, Fujian, China
| | - Xu-Ran Chu
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China
- Department of Medicine II, Internal Medicine, Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, 35392, Giessen, Germany
- Pulmonary and Critical Care, Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, 35392, Giessen, Germany
| | - Xiao-Kun Li
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
| | - Zhou-Guang Wang
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Institute of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Zhejiang, 323000, Lishui, China.
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
| | - Jian-Song Ji
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Institute of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Zhejiang, 323000, Lishui, China.
- Clinical College of the Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, Zhejiang, China.
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Sousa P, Lopes B, Sousa AC, Moreira A, Coelho A, Alvites R, Alves N, Geuna S, Maurício AC. Advancements and Insights in Exosome-Based Therapies for Wound Healing: A Comprehensive Systematic Review (2018-June 2023). Biomedicines 2023; 11:2099. [PMID: 37626596 PMCID: PMC10452374 DOI: 10.3390/biomedicines11082099] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/14/2023] [Accepted: 07/22/2023] [Indexed: 08/27/2023] Open
Abstract
Exosomes have shown promising potential as a therapeutic approach for wound healing. Nevertheless, the translation from experimental studies to commercially available treatments is still lacking. To assess the current state of research in this field, a systematic review was performed involving studies conducted and published over the past five years. A PubMed search was performed for English-language, full-text available papers published from 2018 to June 2023, focusing on exosomes derived from mammalian sources and their application in wound healing, particularly those involving in vivo assays. Out of 531 results, 148 papers were selected for analysis. The findings revealed that exosome-based treatments improve wound healing by increasing angiogenesis, reepithelization, collagen deposition, and decreasing scar formation. Furthermore, there was significant variability in terms of cell sources and types, biomaterials, and administration routes under investigation, indicating the need for further research in this field. Additionally, a comparative examination encompassing diverse cellular origins, types, administration pathways, or biomaterials is imperative. Furthermore, the predominance of rodent-based animal models raises concerns, as there have been limited advancements towards more complex in vivo models and scale-up assays. These constraints underscore the substantial efforts that remain necessary before attaining commercially viable and extensively applicable therapeutic approaches using exosomes.
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Affiliation(s)
- Patrícia Sousa
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - Bruna Lopes
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - Ana Catarina Sousa
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - Alícia Moreira
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - André Coelho
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - Rui Alvites
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
- Instituto Universitário de Ciências da Saúde (CESPU), Avenida Central de Gandra 1317, 4585-116 Paredes, Portugal
| | - Nuno Alves
- Centre for Rapid and Sustainable Product Development, Polytechnic of Leiria, 2430-028 Marinha Grande, Portugal;
| | - Stefano Geuna
- Department of Clinical and Biological Sciences, Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Ospedale San Luigi, 10043 Turin, Italy;
| | - Ana Colette Maurício
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
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Zhu Y, Liao ZF, Mo MH, Xiong XD. Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Vasculopathies and Angiogenesis: Therapeutic Applications and Optimization. Biomolecules 2023; 13:1109. [PMID: 37509145 PMCID: PMC10377109 DOI: 10.3390/biom13071109] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/07/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023] Open
Abstract
Extracellular vesicles (EVs), as part of the cellular secretome, have emerged as essential cell-cell communication regulators in multiple physiological and pathological processes. Previous studies have widely reported that mesenchymal stromal cell-derived EVs (MSC-EVs) have potential therapeutic applications in ischemic diseases or regenerative medicine by accelerating angiogenesis. MSC-EVs also exert beneficial effects on other vasculopathies, including atherosclerosis, aneurysm, vascular restenosis, vascular calcification, vascular leakage, pulmonary hypertension, and diabetic retinopathy. Consequently, the potential of MSC-EVs in regulating vascular homeostasis is attracting increasing interest. In addition to native or naked MSC-EVs, modified MSC-EVs and appropriate biomaterials for delivering MSC-EVs can be introduced to this area to further promote their therapeutic applications. Herein, we outline the functional roles of MSC-EVs in different vasculopathies and angiogenesis to elucidate how MSC-EVs contribute to maintaining vascular system homeostasis. We also discuss the current strategies to optimize their therapeutic effects, which depend on the superior bioactivity, high yield, efficient delivery, and controlled release of MSC-EVs to the desired regions, as well as the challenges that need to be overcome to allow their broad clinical translation.
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Affiliation(s)
- Ying Zhu
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523808, China
- School of Medical Technology, Guangdong Medical University, Dongguan 523808, China
| | - Zhao-Fu Liao
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523808, China
| | - Miao-Hua Mo
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523808, China
| | - Xing-Dong Xiong
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523808, China
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Garima, Sharma D, Kumar A, Mostafavi E. Extracellular vesicle-based biovectors in chronic wound healing: Biogenesis and delivery approaches. MOLECULAR THERAPY. NUCLEIC ACIDS 2023; 32:822-840. [PMID: 37273778 PMCID: PMC10238601 DOI: 10.1016/j.omtn.2023.05.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/29/2023]
Abstract
Chronic wounds remain an unresolved medical issue because of major social and therapeutic repercussions that require extensive focus. Recent related theragnostic focuses only on wound management and is not effectively promoting chronic wound healing. The rising number of patients with either under-healing or over-healing wounds highlights the ineffectiveness of current wound-healing treatments, and thus, there is an unmet need to focus on alternative treatments. To cover this gap, extracellular vesicles (EVs), for targeted delivery of therapeutics, are emerging as a potential therapy to treat both acute and persistent wounds. To address these issues, we explore the core biology of EVs, associated pharmacology, comprehension of immunogenic outcomes, and potential for long-term wound treatment with improved effectiveness and their nonacceptable side effects. Additionally, the therapeutic role of EVs in severe wound infections through biogenetic moderation, in combination with biomaterials (functional in nature), as well as drug carriers that can offer opportunities for the development of new treatments for this long-term condition, are also carefully elaborated, with an emphasis on biomaterial-based drug delivery systems. It is observed that exploring difficulties and potential outcomes of clinical translation of EV-based therapeutics for wound management has the potential to be adopted as a future therapy.
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Affiliation(s)
- Garima
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana 133207, India
| | - Deepika Sharma
- Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Dehradun, India
| | - Arun Kumar
- Department of Pharmacy, School of Health Sciences, Central University of South Bihar, Gaya 824209, India
| | - Ebrahim Mostafavi
- Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
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Qin H, Weng J, Zhou B, Zhang W, Li G, Chen Y, Qi T, Zhu Y, Yu F, Zeng H. Magnesium Ions Promote In Vitro Rat Bone Marrow Stromal Cell Angiogenesis Through Notch Signaling. Biol Trace Elem Res 2023; 201:2823-2842. [PMID: 35870071 DOI: 10.1007/s12011-022-03364-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/15/2022] [Indexed: 11/02/2022]
Abstract
Bone defects are often caused by trauma or surgery and can lead to delayed healing or even bone nonunion, thereby resulting in impaired function of the damaged site. Magnesium ions and related metallic materials play a crucial role in repairing bone defects, but the mechanism remains unclear. In this study, we induced the angiogenic differentiation of bone marrow stromal cells (BMSCs) with different concentrations of magnesium ions. The mechanism was investigated using γ-secretase inhibitor (DAPT) at different time points (7 and 14 days). Angiogenesis, differentiation, migration, and chemotaxis were detected using the tube formation assay, wound-healing assay, and Transwell assay. Besides, we analyzed mRNA expression and the angiogenesis-related protein levels of genes by RT-qPCR and western blot. We discovered that compared with other concentrations, the 5 mM magnesium ion concentration was more conducive to forming tubes. Additionally, hypoxia-inducible factor 1 alpha (Hif-1α) and endothelial nitric oxide (eNOS) expression both increased (p < 0.05). After 7 and 14 days of induction, 5 mM magnesium ion group tube formation, migration, and chemotaxis were enhanced, and the expression of Notch pathway genes increased. Moreover, expression of the Notch target genes hairy and enhancer of split 1 (Hes1) and Hes5 (hairy and enhancer of split 5), as well as the angiogenesis-related genes Hif-1α and eNOS, were enhanced (p < 0.05). However, these trends did not occur when DAPT was applied. This indicates that 5 mM magnesium ion is the optimal concentration for promoting the angiogenesis and differentiation of BMSCs in vitro. By activating the Notch signaling pathway, magnesium ions up-regulate the downstream genes Hes1 and Hes5 and the angiogenesis-related genes Hif-1α and eNOS, thereby promoting the angiogenesis differentiation of BMSCs. Additionally, magnesium ion-induced differentiation enhances the migration and chemotaxis of BMSCs. Thus, we can conclude that magnesium ions and related metallic materials promote angiogenesis to repair bone defects. This provides the rationale for developing artificial magnesium-containing bone materials through tissue engineering.
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Affiliation(s)
- Haotian Qin
- Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, China
| | - Jian Weng
- Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, China
| | - Bo Zhou
- Department of Hand & Microsurgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China
| | - Weifei Zhang
- Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, China
| | - Guoqing Li
- Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, China
| | - Yingqi Chen
- Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, China
| | - Tiantian Qi
- Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, China
| | - Yuanchao Zhu
- Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, China
| | - Fei Yu
- Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
| | - Hui Zeng
- Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
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Bormann D, Gugerell A, Ankersmit HJ, Mildner M. Therapeutic Application of Cell Secretomes in Cutaneous Wound Healing. J Invest Dermatol 2023; 143:893-912. [PMID: 37211377 DOI: 10.1016/j.jid.2023.02.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 02/02/2023] [Accepted: 02/10/2023] [Indexed: 05/23/2023]
Abstract
Although the application of stem cells to chronic wounds emerged as a candidate therapy in the previous century, the mechanism of action remains unclear. Recent evidence has implicated secreted paracrine factors in the regenerative properties of cell-based therapies. In the last two decades, considerable research advances involving the therapeutic potential of stem cell secretomes have expanded the scope of secretome-based therapies beyond stem cell populations. In this study, we review the modes of action of cell secretomes in wound healing, important preconditioning strategies for enhancing their therapeutic efficacy, and clinical trials on secretome-based wound healing.
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Affiliation(s)
- Daniel Bormann
- Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Alfred Gugerell
- Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Hendrik Jan Ankersmit
- Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Michael Mildner
- Department of Dermatology, Medical University of Vienna, Vienna, Austria.
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Lopes D, Lopes J, Pereira-Silva M, Peixoto D, Rabiee N, Veiga F, Moradi O, Guo ZH, Wang XD, Conde J, Makvandi P, Paiva-Santos AC. Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine. Mil Med Res 2023; 10:19. [PMID: 37101293 PMCID: PMC10134679 DOI: 10.1186/s40779-023-00453-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 04/07/2023] [Indexed: 04/28/2023] Open
Abstract
A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes, such as natural cell membranes or subcellular structure-derived membranes. This strategy endows cloaked nanomaterials with improved interfacial properties, superior cell targeting, immune evasion potential, and prolonged duration of systemic circulation. Here, we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials. The structure, properties, and manner in which exosomes communicate with cells are first reviewed. This is followed by a discussion of the types of exosomes and their fabrication methods. We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering, regenerative medicine, imaging, and the treatment of neurodegenerative diseases. Finally, we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.
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Affiliation(s)
- Daniela Lopes
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
| | - Joana Lopes
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
| | - Miguel Pereira-Silva
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
| | - Diana Peixoto
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
| | - Navid Rabiee
- School of Engineering, Macquarie University, Sydney, NSW, 2109, Australia
- Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, 6150, Australia
| | - Francisco Veiga
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
| | - Omid Moradi
- Department of Chemistry, Shahr-e-Qods Branch, Islamic Azad University, Tehran, 374-37515, Iran
| | - Zhan-Hu Guo
- Integrated Composites Laboratory (ICL), Department of Mechanical and Construction Engineering, Northumbria University, Newcastle Upon Tyne, NE1 8ST, UK
| | - Xiang-Dong Wang
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University Shanghai Medical College, Shanghai, 200032, China.
| | - João Conde
- Faculdade de Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal
- Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, Faculdade de Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal
| | - Pooyan Makvandi
- School of Engineering, Institute for Bioengineering, The University of Edinburgh, Edinburgh, EH9 3JL, UK.
| | - Ana Cláudia Paiva-Santos
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal.
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal.
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Ulpiano C, da Silva CL, Monteiro GA. Bioengineered Mesenchymal-Stromal-Cell-Derived Extracellular Vesicles as an Improved Drug Delivery System: Methods and Applications. Biomedicines 2023; 11:biomedicines11041231. [PMID: 37189850 DOI: 10.3390/biomedicines11041231] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/30/2023] [Accepted: 04/12/2023] [Indexed: 05/17/2023] Open
Abstract
Extracellular vesicles (EVs) are cell-derived nano-sized lipid membranous structures that modulate cell-cell communication by transporting a variety of biologically active cellular components. The potential of EVs in delivering functional cargos to targeted cells, their capacity to cross biological barriers, as well as their high modification flexibility, make them promising drug delivery vehicles for cell-free therapies. Mesenchymal stromal cells (MSCs) are known for their great paracrine trophic activity, which is largely sustained by the secretion of EVs. MSC-derived EVs (MSC-EVs) retain important features of the parental cells and can be bioengineered to improve their therapeutic payload and target specificity, demonstrating increased therapeutic potential in numerous pre-clinical animal models, including in the treatment of cancer and several degenerative diseases. Here, we review the fundamentals of EV biology and the bioengineering strategies currently available to maximize the therapeutic value of EVs, focusing on their cargo and surface manipulation. Then, a comprehensive overview of the methods and applications of bioengineered MSC-EVs is presented, while discussing the technical hurdles yet to be addressed before their clinical translation as therapeutic agents.
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Affiliation(s)
- Cristiana Ulpiano
- Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
- Associate Laboratory i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
| | - Cláudia L da Silva
- Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
- Associate Laboratory i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
| | - Gabriel A Monteiro
- Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
- Associate Laboratory i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
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Wang LX, Li YP, Wu SM, Zhang JR, Kong L, Lu B, Liu FW, Li ZY. [Research progress on the role of adipose-derived stem cell exosomes in skin scar formation]. ZHONGHUA SHAO SHANG YU CHUANG MIAN XIU FU ZA ZHI 2023; 39:295-300. [PMID: 37805729 DOI: 10.3760/cma.j.cn501225-20220308-00057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 10/09/2023]
Abstract
The adipose-derived stem cell exosomes are subcellular structures of adipose stem cells. They are nano-sized membrane vesicles that can transport various cell components and act on target cells by paracrine, and they play an important role in the exchanges of substance and information between cells. Scar healing is the commonest way of healing after skin tissue injury. Pathological scar can not only cause movement dysfunction, but also lead to deformity, which affects the appearance of patients and brings life and mental pressure to the patients. In recent years, many researches have shown that the adipose-derived stem cell exosomes contain a variety of bioactive molecules, which play an important role in reducing scar formation and scar-free wound healing, by affecting the proliferation and migration of fibroblasts and the composition of extracellular matrix. This article reviewed the recent literature on the roles and mechanisms of adipose-derived stem cell exosomes in scar formation, and prospected the future application and development of adipose-derived stem cell exosomes in scar treatment.
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Affiliation(s)
- L X Wang
- Basic Medical Science Academy of Air Force Medical University, Xi'an 710032, China
| | - Y P Li
- Department of Oral and Maxillofacial Surgery, the Third Affiliated Hospital of Air Force Medical University, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Xi'an 710032, China
| | - S M Wu
- Department of Oral and Maxillofacial Surgery, the Third Affiliated Hospital of Air Force Medical University, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Xi'an 710032, China
| | - J R Zhang
- Department of Oral and Maxillofacial Surgery, the Third Affiliated Hospital of Air Force Medical University, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Xi'an 710032, China
| | - L Kong
- Department of Oral and Maxillofacial Surgery, the Third Affiliated Hospital of Air Force Medical University, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Xi'an 710032, China
| | - B Lu
- Department of Oral and Maxillofacial Surgery, the Third Affiliated Hospital of Air Force Medical University, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Xi'an 710032, China
| | - F W Liu
- Department of Oral and Maxillofacial Surgery, the Third Affiliated Hospital of Air Force Medical University, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Xi'an 710032, China
| | - Z Y Li
- Department of Oral and Maxillofacial Surgery, the Third Affiliated Hospital of Air Force Medical University, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Xi'an 710032, China
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Joorabloo A, Liu T. Engineering exosome-based biomimetic nanovehicles for wound healing. J Control Release 2023; 356:463-480. [PMID: 36907562 DOI: 10.1016/j.jconrel.2023.03.013] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 03/05/2023] [Accepted: 03/07/2023] [Indexed: 03/14/2023]
Abstract
Complexity and difficulties in wound management are pressing concerns that affect patients' quality of life and may result in tissue infection, necrosis, and loss of local and systemic functions. Hence, novel approaches to accelerate wound healing are being actively explored over the last decade. Exosomes as important mediators of intercellular communications are promising natural nanocarriers due to their biocompatibility, low immunogenicity, drug loading and targeting capacities, and innate stability. More importantly, exosomes are developed as a versatile pharmaceutical engineering platform for wound repair. This review provides an overview of the biological and physiological functions of exosomes derived from a variety of biological origins during wound healing phases, strategies for exosomal engineering, and therapeutic applications in skin regeneration.
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Affiliation(s)
- Alireza Joorabloo
- NICM Health Research Institute, Western Sydney University, Westmead, Australia
| | - Tianqing Liu
- NICM Health Research Institute, Western Sydney University, Westmead, Australia.
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Li H, Li B, Lv D, Li W, Lu Y, Luo G. Biomaterials releasing drug responsively to promote wound healing via regulation of pathological microenvironment. Adv Drug Deliv Rev 2023; 196:114778. [PMID: 36931347 DOI: 10.1016/j.addr.2023.114778] [Citation(s) in RCA: 55] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 12/06/2022] [Accepted: 03/10/2023] [Indexed: 03/17/2023]
Abstract
Wound healing is characterized by complex, orchestrated, spatiotemporal dynamic processes. Recent findings demonstrated suitable local microenvironments were necessities for wound healing. Wound microenvironments include various biological, biochemical and physical factors, which are produced and regulated by endogenous biomediators, exogenous drugs, and external environment. Successful drug delivery to wound is complicated, and need to overcome the destroyed blood supply, persistent inflammation and enzymes, spatiotemporal requirements of special supplements, and easy deactivation of drugs. Triggered by various factors from wound microenvironment itself or external elements, stimuli-responsive biomaterials have tremendous advantages of precise drug delivery and release. Here, we discuss recent advances of stimuli-responsive biomaterials to regulate local microenvironments during wound healing, emphasizing on the design and application of different biomaterials which respond to wound biological/biochemical microenvironments (ROS, pH, enzymes, glucose and glutathione), physical microenvironments (mechanical force, temperature, light, ultrasound, magnetic and electric field), and the combination modes. Moreover, several novel promising drug carriers (microbiota, metal-organic frameworks and microneedles) are also discussed.
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Affiliation(s)
- Haisheng Li
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Buying Li
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Dalun Lv
- Department of Burn and Plastic Surgery, First Affiliated Hospital of Wannan Medical College, Wuhu City, China; Beijing Jayyalife Biological Technology Company, Beijing, China
| | - Wenhong Li
- Beijing Jayyalife Biological Technology Company, Beijing, China
| | - Yifei Lu
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
| | - Gaoxing Luo
- Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
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Amengual-Tugores AM, Ráez-Meseguer C, Forteza-Genestra MA, Monjo M, Ramis JM. Extracellular Vesicle-Based Hydrogels for Wound Healing Applications. Int J Mol Sci 2023; 24:ijms24044104. [PMID: 36835516 PMCID: PMC9967521 DOI: 10.3390/ijms24044104] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
Hydrogels and extracellular vesicle-based therapies have been proposed as emerging therapeutic assets in wound closure. The combination of these elements has given good results in managing chronic and acute wounds. The intrinsic characteristics of the hydrogels in which the extracellular vesicles (EVs) are loaded allow for overcoming barriers, such as the sustained and controlled release of EVs and the maintenance of the pH for their conservation. In addition, EVs can be obtained from different sources and through several isolation methods. However, some barriers must be overcome to transfer this type of therapy to the clinic, for example, the production of hydrogels containing functional EVs and identifying long-term storage conditions for EVs. The aim of this review is to describe the reported EV-based hydrogel combinations, along with the obtained results, and analyze future perspectives.
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Affiliation(s)
- Andreu Miquel Amengual-Tugores
- Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands (UIB), Ctra. Valldemossa km 7.5, 07122 Palma, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Carmen Ráez-Meseguer
- Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands (UIB), Ctra. Valldemossa km 7.5, 07122 Palma, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Maria Antònia Forteza-Genestra
- Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands (UIB), Ctra. Valldemossa km 7.5, 07122 Palma, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Marta Monjo
- Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands (UIB), Ctra. Valldemossa km 7.5, 07122 Palma, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
- Departament de Biologia Fonamental i Ciències de la Salut, University of the Balearic Islands (UIB), 07122 Palma, Spain
- Correspondence: (M.M.); (J.M.R.); Tel.: +34-971-25-96-07 (J.M.R.)
| | - Joana M. Ramis
- Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands (UIB), Ctra. Valldemossa km 7.5, 07122 Palma, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
- Departament de Biologia Fonamental i Ciències de la Salut, University of the Balearic Islands (UIB), 07122 Palma, Spain
- Correspondence: (M.M.); (J.M.R.); Tel.: +34-971-25-96-07 (J.M.R.)
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