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Putri PHL, Alamudi SH, Dong X, Fu Y. Extracellular vesicles in age-related diseases: disease pathogenesis, intervention, and biomarker. Stem Cell Res Ther 2025; 16:263. [PMID: 40437603 PMCID: PMC12121224 DOI: 10.1186/s13287-025-04374-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Accepted: 05/02/2025] [Indexed: 06/01/2025] Open
Abstract
Aging is a multifactorial biological process characterized by the irreversible accumulation of molecular damage, leading to an increased risk of age-related diseases. With the global prominent rise in aging populations, elucidating the mechanisms underlying the aging process and developing strategies to combat age-related diseases have become a pressing priority. Extracellular vesicles (EVs) have gained significant attention due to their role in intercellular communication. EVs are known for their ability to deliver biocargoes, such as miRNA, proteins, and lipids, implicating their involvement in disease pathogenesis and intervention. In this review article, we explore the dual role of EVs in age-related diseases: contributing to the pathogenesis of diseases by transferring deleterious molecules, while also offering therapeutic ability by transferring beneficial molecules. We also highlight the application of EVs as biomarkers for early diagnosis of age-related diseases, paving the way for early intervention and precision medicine. Additionally, we discuss how analysing the composition of EVs cargo can provide insights into disease progression. Finally, we address the challenges and future perspectives of EV-based-therapy in clinical translation, including standardization of EVs isolation methods and improving cargo specificity.
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Affiliation(s)
- Puan Haliza Lintang Putri
- BGI Research, Hangzhou, 310030, China
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok, 16242, Indonesia
| | - Samira Husen Alamudi
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok, 16242, Indonesia
| | - Xuan Dong
- BGI Research, Hangzhou, 310030, China
| | - Ying Fu
- BGI Research, Hangzhou, 310030, China.
- Zhejiang University School of Medicine, Hangzhou, 310058, China.
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Xing Z, Yang W, Zhao C, Wang Y, Jiang X, Qian S, Chu Y, Xia J, Wang C, Wang J. Borate-modified recombinant type XVII collagen microneedles loaded with IGF-1 for the treatment of androgenetic alopecia. Int J Biol Macromol 2025; 314:144460. [PMID: 40398062 DOI: 10.1016/j.ijbiomac.2025.144460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 05/16/2025] [Accepted: 05/19/2025] [Indexed: 05/23/2025]
Abstract
Androgenetic alopecia (AGA), the preeminent form of clinical hair loss, poses a significant challenge to patients. Growth factors (GFs) have been investigated for the treatment of hair loss. However, the issue of their optimal intra-dermal delivery remains a formidable obstacle. Type XVII collagen (COL17), which plays a crucial role in regulating the hair follicle aging process, has emerged as a highly promising candidate for hair loss treatment. Considering these constraints, we developed an IGF-1 loaded borate-modified rhCOL17 MN platform (I-mCOL17 MNs) for the treatment of AGA. The mCOL17 MNs are engineered to precisely control the release of bioactive payloads in response to dynamic changes in the microenvironment. A comprehensive investigation was conducted to verify the physicochemical characteristics, as well as the in vitro and in vivo biological activities of the MNs. Our findings demonstrate that, when contrasted with the clinically utilized drug minoxidil, our MN exhibits a remarkable capacity to enhance neovascularization, alleviate tissue-based inflammatory responses, and promote hair regeneration in murine models of AGA. Overall, this MN represents a novel, safer, and more efficient strategy for the treatment of AGA, offering new hope for patients suffering from this prevalent condition.
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Affiliation(s)
- Zheng Xing
- School of Pharmacy & School of Medical and Health Engineering, Changzhou University, Changzhou, Jiangsu 213164, PR China; Department of Pharmacy, The Second People's Hospital of Changzhou, The Third Affliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213004, PR China
| | - Wenhao Yang
- School of Pharmacy & School of Medical and Health Engineering, Changzhou University, Changzhou, Jiangsu 213164, PR China
| | - Chen Zhao
- Department of Pharmacy, The Second People's Hospital of Changzhou, The Third Affliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213004, PR China
| | - Yuhui Wang
- School of Pharmacy & School of Medical and Health Engineering, Changzhou University, Changzhou, Jiangsu 213164, PR China
| | - Xiaolian Jiang
- School of Pharmacy & School of Medical and Health Engineering, Changzhou University, Changzhou, Jiangsu 213164, PR China
| | - Song Qian
- Jiangsu Trautec Medical Technology Co., Ltd, Changzhou, Jiangsu 213200, PR China
| | - Yun Chu
- Jiangsu Trautec Medical Technology Co., Ltd, Changzhou, Jiangsu 213200, PR China
| | - Jiang Xia
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Cheng Wang
- School of Pharmacy & School of Medical and Health Engineering, Changzhou University, Changzhou, Jiangsu 213164, PR China.
| | - Jianhao Wang
- School of Pharmacy & School of Medical and Health Engineering, Changzhou University, Changzhou, Jiangsu 213164, PR China.
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Fu J, Wang D, Liu W, Qi Y, Zhang C, Li H, Cai J, Ji S, Zhang L, Sun F. miR-370-3p Inhibited the Proliferation of Sheep Dermal Papilla Cells by Inhibiting the Expression of SMAD4. Cells 2025; 14:714. [PMID: 40422217 DOI: 10.3390/cells14100714] [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: 04/27/2025] [Revised: 05/12/2025] [Accepted: 05/12/2025] [Indexed: 05/28/2025] Open
Abstract
The proliferation and maturation of hair follicles in follicular papilla cells are predominantly governed by miRNAs, which significantly influence the cell cycle, apoptosis, and proliferation. miR-370-3p has been associated with several biological processes and targets SMAD4, a crucial component in hair follicle development. Tissue expression profiling revealed significant differences in miR-370-3p levels between skin tissues of the two sheep breeds in January and October, as well as between tissues of the Xinji fine-wool sheep and Small-tail Han sheep. SMAD4 exhibited significant differences in tissue-specific expression in the heart, spleen, skin, lungs, and muscles from Xinji fine-wool sheep and Small-tail Han sheep. Bioinformatics analysis and dual-luciferase reporter assays validated the regulatory interaction between miR-370-3p and SMAD4. CCK-8 experiments demonstrated that miR-370-3p's targeting of SMAD4 suppressed cell growth. Cell cycle analysis demonstrated that miR-370-3p's targeting of SMAD4 influenced the cell cycle. Annexin V-FITC/PI dual labeling demonstrated that miR-370-3p's targeting of SMAD4 promoted cell apoptosis. RT-qPCR data demonstrated that miR-370-3p's targeting of SMAD4 elevated the expression of JUN, c-MYC, and TCF7L2 while suppressing β-catenin expression. Western blot (WB) analysis demonstrated that miR-370-3p targeting of SMAD4 significantly promoted c-MYC expression while inhibiting CCND1, CCND2, and β-catenin expression. miR-370-3p and SMAD4 exhibit spatiotemporal expression differences in sheep skin tissues, with widespread expression across various tissues. Furthermore, it confirmed that miR-370-3p targets SMAD4 to inhibit follicular papilla cell proliferation, promote apoptosis, and influence the cell cycle.
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Affiliation(s)
- Jiaqi Fu
- College of Agriculture, Yanbian University, Yanji 133002, China
| | - Dan Wang
- College of Agriculture, Yanbian University, Yanji 133002, China
- Animal Disease Prevention and Control Center of Panshi City, Panshi 132300, China
| | - Wenqing Liu
- College of Agriculture, Yanbian University, Yanji 133002, China
| | - Yu Qi
- College of Agriculture, Yanbian University, Yanji 133002, China
- Animal Biotechnology Institute, Jilin Academy of Agricultural Sciences, Gongzhuling 136100, China
| | - Caihong Zhang
- College of Agriculture, Yanbian University, Yanji 133002, China
- Animal Biotechnology Institute, Jilin Academy of Agricultural Sciences, Gongzhuling 136100, China
| | - Huansong Li
- College of Agriculture, Yanbian University, Yanji 133002, China
| | - Jinshun Cai
- College of Agriculture, Yanbian University, Yanji 133002, China
| | - Shuang Ji
- College of Agriculture, Yanbian University, Yanji 133002, China
| | - Lichun Zhang
- Animal Biotechnology Institute, Jilin Academy of Agricultural Sciences, Gongzhuling 136100, China
| | - Fuliang Sun
- College of Agriculture, Yanbian University, Yanji 133002, China
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Li X, Liu X, Li B, Liu Z, Guo S, Xiong S, Xiao T, Jiao S, Chen Y, Xu Y. Identifying the active components and mechanisms of Persicae Semen in treating androgenetic alopecia: Insights from network pharmacology and experimental evaluations. JOURNAL OF ETHNOPHARMACOLOGY 2025; 347:119755. [PMID: 40220939 DOI: 10.1016/j.jep.2025.119755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/22/2025] [Accepted: 04/04/2025] [Indexed: 04/14/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Androgenic alopecia (AGA) is the most prevalent form of hair loss, which affects self-perception and life satisfaction. Current treatments for AGA are limited. In Traditional Chinese Medicine, Persicae Semen (Taoren, TR) is used in formula to mitigate alopecia. However, the principal active constituents and their mechanisms of action in anti-alopecia effects remain fully undefined. AIM OF THE STUDY This study aimed to elucidate the active constituents and multifaceted mechanisms of TR in AGA treatment through network pharmacology analysis, molecular docking, and experimental validation. MATERIALS AND METHODS The chemical constituents of TR were systematically characterized using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In addition, a comprehensive compound-disease-target interaction network was constructed to elucidate the molecular mechanism underlying its therapeutic effects on AGA. Molecular docking was performed to validate the interactions between the key bioactive components and core targets. Furthermore, a multi-level pharmacological investigation comprising in vitro cellular assays, ex vivo organ studies, and in vivo animal experiments was conducted to preliminarily explore the therapeutic mechanisms by which high-content active compound treated AGA. RESULTS UPLC-Q-TOF-MS analysis identified 32 chemical constituents in TR. Through integrated network pharmacology analysis, six bioactive components and 10 core targets were systematically screened for molecular docking, which revealed therapeutic pathways primarily involved in anti-inflammatory responses, angiogenesis, and hair follicle microenvironment modulation. Given its high abundance and superior bioactivity, amygdalin (Am) was selected as the primary research focus. Combined with the pathological mechanism of the disease, which was confirmed through in vitro and in vivo experiments, Am promoted hair regeneration by regulating genes, proteins and inflammatory factors related to the androgen, Wnt/β-catenin, and vascular endothelial growth factor pathways. CONCLUSIONS In this study the multi-component, multi-target, and multi-pathway mechanisms underlying the therapeutic effects of TR on AGA as well as the molecular mechanism by which Am treats AGA was elucidated. These findings provide substantial theoretical foundations and experimental evidence for the development of novel AGA therapeutics based on TR and its active constituents.
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Affiliation(s)
- Xiaojuan Li
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China; Pharmacy School of Shihezi University, Xinjiang, 832000, China.
| | - Xiaoli Liu
- Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China.
| | - Bin Li
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
| | - Ziyi Liu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
| | - Shiqi Guo
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
| | - Sha Xiong
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
| | - Ting Xiao
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
| | - Siwen Jiao
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
| | - Yu Chen
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
| | - Yuehong Xu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
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Zhang M, Pang X, Kang S, Sui H, Kong X, Wang G, Wang R, Shen G, Tian Q. Minoxidil cyclodextrin inclusion complex-loaded microemulsions and transfersomes for androgen alopecia treatment: a comparative study. Drug Deliv Transl Res 2025:10.1007/s13346-025-01851-7. [PMID: 40210806 DOI: 10.1007/s13346-025-01851-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/30/2025] [Indexed: 04/12/2025]
Abstract
Our MXD/SCD@TF designed by the combination of transfersome and inclusion technology was obviously superior to commercial 2% MXD tincture in treating androgenetic alopecia (AGA) in mice, but its complex preparation and poor stability undoubtedly increased both development and usage costs. In this paper, using our previous alcohol-free low surfactant microemulsion technology with VES as auxiliary oil phase, microemulsions loaded with the inclusion complex of MXD and sulfobutylether-β-cyclodextrin (SBE-β-CD) were prepared, optimized and characterized, and the therapeutic effect on AGA C57BL/6 mice was compared with MXD/SCD@TF. According to the ternary phase diagram, steady-state permeation rate of MXD through SD rat skin and drug retention, MXD/SCD@ME was selected as the optimal prescription, composed of 5.25% oil phase, 9.75% surfactants, 10.20% SBE-β-CD, 1.02% MXD and 73.78% water, which conformed to the characteristics of microemulsion. MXD/SCD@ME had good stability, and the application of inclusion technology increased the MXD loading in microemulsion to nearly 5 times. The results of in vivo skin penetration test and laser confocal scanning visualization showed that MXD/SCD@ME was easier to deliver drugs to deeper skin tissues than MXD/SCD@TF. Hair regeneration study demonstrated that MXD/SCD@ME had higher ability than MXD/SCD@TF in promoting hair growth, prolonging hair growth period, reducing ROS level and promoting cell proliferation of hair follicles. In addition, the blank microemulsion of MXD/SCD@ME had certain therapeutic effect on AGA, indicating the synergistic effect between VES and MXD. All these indicated that MXD/SCD@ME is expected to provide a better choice for pharmacological therapy of MXD on AGA than MXD/SCD@TF.
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Affiliation(s)
- Min Zhang
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, China
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, China
| | - Xiaoya Pang
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, China
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, China
| | - Shuhui Kang
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, China
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, China
| | - Hao Sui
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, China
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, China
| | - Xia Kong
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, China
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, China
| | - Gang Wang
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, China
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, China
| | - Ruixuan Wang
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, China
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, China
| | - Guiqing Shen
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, China
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, China
| | - Qingping Tian
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, China.
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, China.
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Hamida OB, Kim MK, Sung YK, Kim MK, Kwack MH. Hair Regeneration Methods Using Cells Derived from Human Hair Follicles and Challenges to Overcome. Cells 2024; 14:7. [PMID: 39791708 PMCID: PMC11720663 DOI: 10.3390/cells14010007] [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: 11/15/2024] [Revised: 12/12/2024] [Accepted: 12/23/2024] [Indexed: 01/12/2025] Open
Abstract
The hair follicle is a complex of mesenchymal and epithelial cells acquiring different properties and characteristics responsible for fulfilling its inductive and regenerative role. The epidermal and dermal crosstalk induces morphogenesis and maintains hair follicle cycling properties. The hair follicle is enriched with pluripotent stem cells, where dermal papilla (DP) cells and dermal sheath (DS) cells constitute the dermal compartment and the epithelial stem cells existing in the bulge region exert their regenerative role by mediating the epithelial-mesenchymal interaction (EMI). Many studies have developed and focused on various methods to optimize the EMI through in vivo and in vitro approaches for hair regeneration. The culturing of human hair mesenchymal cells resulted in the loss of trichogenicity and inductive properties of DP cells, limiting their potential application in de novo hair follicle generation in vivo. Epithelial stem cells derived from human hair follicles are challenging to isolate and culture, making it difficult to obtain enough cells for hair regeneration purposes. Mesenchymal stem cells and epithelial stem cells derived from human hair follicles lose their ability to form hair follicles during culture, limiting the study of hair follicle formation in vivo. Therefore, many attempts and methods have been developed to overcome these limitations. Here, we review the possible and necessary cell methods and techniques used for human hair follicle regeneration and the restoration of hair follicle cell inductivity in culture.
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Affiliation(s)
- Ons Ben Hamida
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; (O.B.H.); (M.K.K.); (Y.K.S.); (M.K.K.)
| | - Moon Kyu Kim
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; (O.B.H.); (M.K.K.); (Y.K.S.); (M.K.K.)
- Hair Transplantation Center, Kyungpook National University Hospital, Daegu 41944, Republic of Korea
| | - Young Kwan Sung
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; (O.B.H.); (M.K.K.); (Y.K.S.); (M.K.K.)
| | - Min Kyu Kim
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; (O.B.H.); (M.K.K.); (Y.K.S.); (M.K.K.)
| | - Mi Hee Kwack
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; (O.B.H.); (M.K.K.); (Y.K.S.); (M.K.K.)
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Ren Y, Li A, Miao X, Huo L, Qin H, Jiang H, Liu M. Effects of photobiomodulation on human hair dermal papilla cells with various light modes and light parameters. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2024; 262:113080. [PMID: 39689407 DOI: 10.1016/j.jphotobiol.2024.113080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 11/27/2024] [Accepted: 12/04/2024] [Indexed: 12/19/2024]
Abstract
Androgenetic alopecia (AGA) is a prevalent hair loss disorder and influenced by genetic, hormonal, and environmental factors. Minoxidil and finasteride have been widely used for treating AGA. However, the side effects associated with these drugs often lead to poor patient compliance. In contrast, photobiomodulation (PBM), due to its safety and non-invasiveness, holds promising prospects for use. Although the promoting effects of PBM on AGA have been reported, the mechanisms by which PBM affects dermal papilla cells (DPCs) remain largely unknown. Hence, this study explored the impacts of both continuous wave (CW) and pulsed wave (PW) PBM on DPCs, and revealed the underlying actions of light parameters in PBM. Orthogonal experiments were conducted to evaluate the effects of CW PBM on DPCs at varying irradiances and doses, indicating that irradiance was the crucial parameter, as well as cell viability and proliferation were maximized at 8 mW/cm2 and 8 J/cm2. For PW PBM, response surface methodology was employed to determine the influences of duty cycles, frequencies, and doses. The findings highlighted frequency as a primary factor, with the optimum cell viability observed at peak irradiance 10 mW/cm2, duty cycle 80 %, 500 Hz, and 8.8 J/cm2. Notably, PBM could enhance cell viability, proliferation, and migration in DPCs by activating the Wnt/β-Catenin signaling and suppressing Transforming Growth Factor signaling, particularly when applied in pulsed mode. Overall, this study determined the key light parameters that influence PBM effectiveness, further identified the optimal light conditions, and preliminary revealed into the mechanisms of PBM in DPCs, highlighting that PW PBM may be a competitive therapeutic option for alleviating AGA in the future.
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Affiliation(s)
- Yi Ren
- School of information science and technology, Fudan University, 2005th Songhu Rd, Shanghai 200438, China
| | - Angze Li
- School of information science and technology, Fudan University, 2005th Songhu Rd, Shanghai 200438, China
| | - Xiaojing Miao
- School of information science and technology, Fudan University, 2005th Songhu Rd, Shanghai 200438, China
| | - Longfei Huo
- School of information science and technology, Fudan University, 2005th Songhu Rd, Shanghai 200438, China
| | - Haokuan Qin
- Academy for Engineering and Technology, Fudan University, 220th Handan Rd, Shanghai 200433, China
| | - Hui Jiang
- Academy for Engineering and Technology, Fudan University, 220th Handan Rd, Shanghai 200433, China
| | - Muqing Liu
- School of information science and technology, Fudan University, 2005th Songhu Rd, Shanghai 200438, China; Zhongshan Fudan Joint Innovation Center, 6th Xiangxing Rd, Zhongshan City, Guangdong Province 528403, China.
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8
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Wang M, Hong Y, Fu X, Sun X. Advances and applications of biomimetic biomaterials for endogenous skin regeneration. Bioact Mater 2024; 39:492-520. [PMID: 38883311 PMCID: PMC11179177 DOI: 10.1016/j.bioactmat.2024.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 04/11/2024] [Accepted: 04/11/2024] [Indexed: 06/18/2024] Open
Abstract
Endogenous regeneration is becoming an increasingly important strategy for wound healing as it facilitates skin's own regenerative potential for self-healing, thereby avoiding the risks of immune rejection and exogenous infection. However, currently applied biomaterials for inducing endogenous skin regeneration are simplistic in their structure and function, lacking the ability to accurately mimic the intricate tissue structure and regulate the disordered microenvironment. Novel biomimetic biomaterials with precise structure, chemical composition, and biophysical properties offer a promising avenue for achieving perfect endogenous skin regeneration. Here, we outline the recent advances in biomimetic materials induced endogenous skin regeneration from the aspects of structural and functional mimicry, physiological process regulation, and biophysical property design. Furthermore, novel techniques including in situ reprograming, flexible electronic skin, artificial intelligence, single-cell sequencing, and spatial transcriptomics, which have potential to contribute to the development of biomimetic biomaterials are highlighted. Finally, the prospects and challenges of further research and application of biomimetic biomaterials are discussed. This review provides reference to address the clinical problems of rapid and high-quality skin regeneration.
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Affiliation(s)
- Mengyang Wang
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, 100853, PR China
- PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing, 100089, PR China
| | - Yiyue Hong
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, 100853, PR China
- PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing, 100089, PR China
| | - Xiaobing Fu
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, 100853, PR China
- PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing, 100089, PR China
- Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, PR China
| | - Xiaoyan Sun
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, 100853, PR China
- PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing, 100089, PR China
- Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, PR China
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9
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Jiang Z, Cheng H, Qian X, Tu J, Fan C, Pan Y, Lin Z, Chen J, Wang X, Zhang J. The role and mechanism of engineered nanovesicles derived from hair follicle mesenchymal stem cells in the treatment of UVB-induced skin photoaging. J Cosmet Dermatol 2024; 23:3005-3020. [PMID: 38769897 DOI: 10.1111/jocd.16336] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 03/06/2024] [Accepted: 04/10/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are effective in the treatment of skin photoaging; however, their low yield and functional decline with passage progression limit their clinical application. Cell-derived nanovesicles (CNVs) are potential alternatives that can address the limitations of EVs derived from MSCs and are conducive to clinical transformations. Hair follicle mesenchymal stem cells (HFMSCs), a type of MSCs, have demonstrated the function of repairing skin tissues; nevertheless, the efficacy of CNVs from HFMSCs (HFMSC-CNVs) in the treatment of skin photoaging remains unclear. Therefore, ultraviolet radiation B (UVB)-induced photoaging nude mice and human dermal fibroblasts (HDFs) were used as experimental models to investigate the therapeutic effects of HFMSC-CNVs in photoaging models. METHODS HFMSC-CNVs were successfully prepared using the mechanical extrusion method. UVB-induced nude mice and HDFs were used as experimental models of photoaging. Multiple approaches, including hematoxylin-eosin and Masson staining, immunohistochemistry, immunofluorescence, detection of reactive oxygen species (ROS), flow cytometry, western blotting, and other experimental methods, were combined to investigate the possible effects and mechanisms of HFMSC-CNVs in the treatment of skin photoaging. RESULTS In the nude mouse model of skin photoaging, treatment with HFMSC-CNVs reduced UVB-induced skin wrinkles (p < 0.05) and subcutaneous capillary dilation, alleviated epidermis thickening (p < 0.001), and dermal thinning (p < 0.001). Furthermore, HFMSC-CNVs upregulated proliferating cell nuclear antigen (PCNA) expression (p < 0.05) and decreased the levels of ROS, β-galactosidase (β-Gal), and CD86 (p < 0.01). In vitro experiments, treatment with HFMSC-CNVs enhanced the cellular activity of UVB-exposed HDFs (p < 0.05), and reduced ROS levels and the percentage of senescent cells (p < 0.001), and alleviated cell cycle arrest (p < 0.001). HFMSC-CNVs upregulated the expression of Collagen I (Col I), SMAD2/3, transforming growth factor beta (TGF-β), catalase (CAT), glutathione peroxidase-1 (GPX-1), and superoxide dismutase-1 (SOD-1) (p < 0.05) and downregulated the expression of cycle suppressor protein (p53), cell cycle suppressor protein (p21), and matrix metalloproteinase 3 (MMP3) (p < 0.05). CONCLUSION Conclusively, the anti-photoaging properties of HFMSC-CNVs were confirmed both in vivo and in vitro. HFMSC-CNVs exert anti-photoaging effects by alleviating cell cycle arrest, decreasing cellular senescence and macrophage infiltration, promoting cell proliferation and extracellular matrix (ECM) production, and reducing oxidative stress by increasing the activity of antioxidant enzymes.
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Affiliation(s)
- Zhounan Jiang
- Affiliated Hangzhou First People's Hospital, School Of Medicine, Westlake University, Hangzhou, China
- The Second Affiliated Hospital Zhejiang University School Of Medicine, Hangzhou, China
| | - Hanxiao Cheng
- Affiliated Hangzhou First People's Hospital, School Of Medicine, Westlake University, Hangzhou, China
| | - Xifei Qian
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jingyi Tu
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Chongxiang Fan
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yirui Pan
- Affiliated Hangzhou First People's Hospital, School Of Medicine, Westlake University, Hangzhou, China
| | - Zhiwei Lin
- Zhejiang Healthfuture Biomedicine Co., Ltd., Hangzhou, China
| | - Jinyang Chen
- Zhejiang Healthfuture Biomedicine Co., Ltd., Hangzhou, China
| | - Xiangsheng Wang
- Affiliated Hangzhou First People's Hospital, School Of Medicine, Westlake University, Hangzhou, China
| | - Jufang Zhang
- Affiliated Hangzhou First People's Hospital, School Of Medicine, Westlake University, Hangzhou, China
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Cheng M, Ma C, Chen HD, Wu Y, Xu XG. The Roles of Exosomes in Regulating Hair Follicle Growth. Clin Cosmet Investig Dermatol 2024; 17:1603-1612. [PMID: 38984321 PMCID: PMC11232880 DOI: 10.2147/ccid.s465963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 06/08/2024] [Indexed: 07/11/2024]
Abstract
Alopecia is considered a widespread yet troubling health issue, with limited treatment options. As membranous structures derived from cells carrying proteins, nucleic acids and lipids, exosomes functionally medicate intercellular communication and alter the responses of recipient cells, resulting in disease restraint or promotion. Exosomes have broad prospects in diagnosis and treatment of diseases. Studies using animal models and at the cellular level have clearly shown that exosomes from several types of cells, including dermal papilla cells and mesenchymal stem cells, have a notable capacity to promote hair growth, suggesting that exosomes may provide a new option to treat alopecia. Here, we present a thorough review of the most recent progress in the application of exosomes to hair growth.
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Affiliation(s)
- Ming Cheng
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110000, People’s Republic of China
- Key Laboratory of Immunodermatology, Ministry of Education and NHC; National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, Shenyang, 110000, People’s Republic of China
| | - Cong Ma
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110000, People’s Republic of China
- Key Laboratory of Immunodermatology, Ministry of Education and NHC; National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, Shenyang, 110000, People’s Republic of China
- Department of Dermatology and Sexually Transmitted Diseases, The First Hospital of Inner Mongolia University for Nationalities, Tongliao, 028000, People’s Republic of China
| | - Hong-Duo Chen
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110000, People’s Republic of China
- Key Laboratory of Immunodermatology, Ministry of Education and NHC; National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, Shenyang, 110000, People’s Republic of China
| | - Yan Wu
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110000, People’s Republic of China
- Key Laboratory of Immunodermatology, Ministry of Education and NHC; National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, Shenyang, 110000, People’s Republic of China
| | - Xue-Gang Xu
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110000, People’s Republic of China
- Key Laboratory of Immunodermatology, Ministry of Education and NHC; National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, Shenyang, 110000, People’s Republic of China
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11
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Zhang W, Hou Y, Yin S, Miao Q, Lee K, Zhou X, Wang Y. Advanced gene nanocarriers/scaffolds in nonviral-mediated delivery system for tissue regeneration and repair. J Nanobiotechnology 2024; 22:376. [PMID: 38926780 PMCID: PMC11200991 DOI: 10.1186/s12951-024-02580-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 05/24/2024] [Indexed: 06/28/2024] Open
Abstract
Tissue regeneration technology has been rapidly developed and widely applied in tissue engineering and repair. Compared with traditional approaches like surgical treatment, the rising gene therapy is able to have a durable effect on tissue regeneration, such as impaired bone regeneration, articular cartilage repair and cancer-resected tissue repair. Gene therapy can also facilitate the production of in situ therapeutic factors, thus minimizing the diffusion or loss of gene complexes and enabling spatiotemporally controlled release of gene products for tissue regeneration. Among different gene delivery vectors and supportive gene-activated matrices, advanced gene/drug nanocarriers attract exceptional attraction due to their tunable physiochemical properties, as well as excellent adaptive performance in gene therapy for tissue regeneration, such as bone, cartilage, blood vessel, nerve and cancer-resected tissue repair. This paper reviews the recent advances on nonviral-mediated gene delivery systems with an emphasis on the important role of advanced nanocarriers in gene therapy and tissue regeneration.
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Affiliation(s)
- Wanheng Zhang
- Institute of Geriatrics, School of Medicine, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Shanghai University, Shanghai, 200444, China
- Department of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China
| | - Yan Hou
- Institute of Geriatrics, School of Medicine, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Shanghai University, Shanghai, 200444, China
- Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), Shanghai University, Shanghai, 200444, China
| | - Shiyi Yin
- Department of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China
| | - Qi Miao
- Department of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China
| | - Kyubae Lee
- Department of Biomedical Materials, Konyang University, Daejeon, 35365, Republic of Korea
| | - Xiaojian Zhou
- Department of Pediatrics, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China.
| | - Yongtao Wang
- Institute of Geriatrics, School of Medicine, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Shanghai University, Shanghai, 200444, China.
- Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), Shanghai University, Shanghai, 200444, China.
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Si Y, Hayat MA, Hu J. NSPCs-ES: mechanisms and functional impact on central nervous system diseases. Biomed Mater 2024; 19:042011. [PMID: 38916246 DOI: 10.1088/1748-605x/ad5819] [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: 01/04/2024] [Accepted: 06/13/2024] [Indexed: 06/26/2024]
Abstract
Patients with central neuronal damage may suffer severe consequences, but effective therapies remain unclear. Previous research has established the transplantation of neural stem cells that generate new neurons to replace damaged ones. In a new field of scientific research, the extracellular secretion of NPSCs (NSPCs-ES) has been identified as an alternative to current chemical drugs. Many preclinical studies have shown that NSPCs-ES are effective in models of various central nervous system diseases (CNS) injuries, from maintaining functional structures at the cellular level to providing anti-inflammatory functions at the molecular level, as well as improving memory and motor functions, reducing apoptosis in neurons, and mediating multiple signaling pathways. The NSPC-ES can travel to the damaged tissue and exert a broad range of therapeutic effects by supporting and nourishing damaged neurons. However, gene editing and cell engineering techniques have recently improved therapeutic efficacy by modifying NSPCs-ES. Consequently, future research and application of NSPCs-ES may provide a novel strategy for the treatment of CNS diseases in the future. In this review, we summarize the current progress on these aspects.
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Affiliation(s)
- Yu Si
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, People's Republic of China
- Institute of Cerebrovascular Disease, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, People's Republic of China
| | - Muhammad Abid Hayat
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, People's Republic of China
- Institute of Cerebrovascular Disease, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, People's Republic of China
| | - Jiabo Hu
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, People's Republic of China
- Institute of Cerebrovascular Disease, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, People's Republic of China
- Zhenjiang Blood Center, Zhenjiang, Jiangsu 212013, People's Republic of China
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13
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Lousada MB, Edelkamp J, Lachnit T, Fehrholz M, Pastar I, Jimenez F, Erdmann H, Bosch TCG, Paus R. Spatial Distribution and Functional Impact of Human Scalp Hair Follicle Microbiota. J Invest Dermatol 2024; 144:1353-1367.e15. [PMID: 38070726 DOI: 10.1016/j.jid.2023.11.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 10/17/2023] [Accepted: 11/01/2023] [Indexed: 02/26/2024]
Abstract
Human hair follicles (HFs) constitute a unique microbiota habitat that differs substantially from the skin surface. Traditional HF sampling methods fail to eliminate skin microbiota contaminants or assess the HF microbiota incompletely, and microbiota functions in human HF physiology remain ill explored. Therefore, we used laser-capture microdissection, metagenomic shotgun sequencing, and FISH to characterize the human scalp HF microbiota in defined anatomical compartments. This revealed significant compartment-, tissue lineage-, and donor age-dependent variations in microbiota composition. Greatest abundance variations between HF compartments were observed for viruses, archaea, Staphylococcus epidermidis, Cutibacterium acnes, and Malassezia restricta, with the latter 2 being the most abundant viable HF colonizers (as tested by propidium monoazide assay) and, surprisingly, most abundant in the HF mesenchyme. Transfection of organ-cultured human scalp HFs with S. epidermidis-specific lytic bacteriophages ex vivo downregulated transcription of genes known to regulate HF growth and development, metabolism, and melanogenesis, suggesting that selected microbial products may modulate HF functions. Indeed, HF treatment with butyrate, a metabolite of S. epidermidis and other HF microbiota, delayed catagen and promoted autophagy, mitochondrial activity, and gp100 and dermcidin expression ex vivo. Thus, human HF microbiota show spatial variations in abundance and modulate the physiology of their host, which invites therapeutic targeting.
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Affiliation(s)
- Marta B Lousada
- Monasterium Laboratory, Münster, Germany; Zoological Institute, Christian Albrechts University in Kiel, Kiel, Germany
| | | | - Tim Lachnit
- Zoological Institute, Christian Albrechts University in Kiel, Kiel, Germany
| | | | - Irena Pastar
- Dr Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Francisco Jimenez
- Mediteknia Skin & Hair Lab, Las Palmas de Gran Canaria, Spain; Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain
| | | | - Thomas C G Bosch
- Zoological Institute, Christian Albrechts University in Kiel, Kiel, Germany
| | - Ralf Paus
- Monasterium Laboratory, Münster, Germany; Dr Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA; CUTANEON, Hamburg, Germany.
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Liu X, Kong X, Xu L, Su Y, Xu S, Pang X, Wang R, Ma Y, Tian Q, Han L. Synergistic therapeutic effect of ginsenoside Rg3 modified minoxidil transfersomes (MXD-Rg3@TFs) on androgenic alopecia in C57BL/6 mice. Int J Pharm 2024; 654:123963. [PMID: 38430952 DOI: 10.1016/j.ijpharm.2024.123963] [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: 10/11/2023] [Revised: 02/14/2024] [Accepted: 02/28/2024] [Indexed: 03/05/2024]
Abstract
Inflammation in hair follicles will reduce the effectiveness of minoxidil (MXD) in the treatment of androgen alopecia (AGA) caused by elevated androgen levels. To target multiple physiological and pathological processes in AGA, a novel natural bioactive compound modified transfersomes (MXD-Rg3@TFs) was prepared to replace cholesterol that may disrupt hair growth, with ginsenosides Rg3 (Rg3) that have anti-inflammatory effects on AGA. The effects of MXD, Rg3 and their combination on AGA were evaluated using dihydrotestosterone (DHT) induced human dermal papilla cells (DPCs), and the results showed that the combination of MXD and Rg3 can significantly promote the proliferation, reduce the level of intracellular ROS and inflammatory factors, and inhibit the aging of DHT induced DPCs. Compared with cholesterol membrane transfersomes (MXD-Ch@TFs), MXD-Rg3@TFs has similar deformability, smaller particle size and better stability. MXD-Rg3@TFs has also significant advantages in shortening telogen phase and prolonging the growth period of hair follicles in C57BL/6 mice than MXD-Ch@TFs and commercial MXD tincture. The prominent ability of MXD-Rg3@TFs to inhibit the conversion of testosterone to DHT and reduce the level of inflammatory factors suggested that Rg3 and MXD in MXD-Rg3@TFs have synergistic effect on AGA therapy. MXD-Ch@TFs with no irritation to C57BL/6 mice skin is expected to reduce the dose of MXD and shorten the treatment time, which would undoubtedly provide a promising therapeutic option for treatment of AGA.
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Affiliation(s)
- Xiaxia Liu
- School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; School of Pharmacy & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China
| | - Xia Kong
- School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China
| | - Li Xu
- School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China
| | - Yonghui Su
- School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; School of Pharmacy & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China
| | - Shanshan Xu
- School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; School of Pharmacy & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China
| | - Xiaoya Pang
- School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China
| | - Ruifen Wang
- School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; School of Pharmacy & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China
| | - Yihan Ma
- School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; School of Pharmacy & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China
| | - Qingping Tian
- School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China.
| | - Liwen Han
- School of Pharmacy & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China.
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Jiang Y, Yu M, Song ZF, Wei ZY, Huang J, Qian HY. Targeted Delivery of Mesenchymal Stem Cell-Derived Bioinspired Exosome-Mimetic Nanovesicles with Platelet Membrane Fusion for Atherosclerotic Treatment. Int J Nanomedicine 2024; 19:2553-2571. [PMID: 38505171 PMCID: PMC10949310 DOI: 10.2147/ijn.s452824] [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: 12/13/2023] [Accepted: 03/05/2024] [Indexed: 03/21/2024] Open
Abstract
Purpose Accumulating evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes hold significant potential for the treatment of atherosclerosis. However, large-scale production and organ-specific targeting of exosomes are still challenges for further clinical applications. This study aims to explore the targeted efficiency and therapeutic potential of biomimetic platelet membrane-coated exosome-mimetic nanovesicles (P-ENVs) in atherosclerosis. Methods To produce exosome-mimetic nanovesicles (ENVs), MSCs were successively extruded through polycarbonate porous membranes. P-ENVs were engineered by fusing MSC-derived ENVs with platelet membranes and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. The stability and safety of P-ENVs were also assessed. The targeted efficacy of P-ENVs was evaluated using an in vivo imaging system (IVIS) spectrum imaging system and immunofluorescence. Histological analyses, Oil Red O (ORO) staining, and Western blot were used to investigate the anti-atherosclerotic effectiveness of P-ENVs. Results Both ENVs and P-ENVs exhibited similar characteristics to exosomes. Subsequent miRNA sequencing of P-ENVs revealed their potential to mitigate atherosclerosis by influencing biological processes related to cholesterol metabolism. In an ApoE-/- mice model, the intravenous administration of P-ENVs exhibited enhanced targeting of atherosclerotic plaques, resulting in a significant reduction in lipid deposition and necrotic core area. Our in vitro experiments showed that P-ENVs promoted cholesterol efflux and reduced total cholesterol content in foam cells. Further analysis revealed that P-ENVs attenuated intracellular cholesterol accumulation by upregulating the expression of the critical cholesterol transporters ABCA1 and ABCG1. Conclusion This study highlighted the potential of P-ENVs as a novel nano-drug delivery platform for enhancing drug delivery efficiency while concurrently mitigating adverse reactions in atherosclerotic therapy.
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Affiliation(s)
- Yu Jiang
- Center for Coronary Heart Disease, Department of Cardiology, Fu Wai Hospital, National Center for Cardiovascular Diseases of China, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Miao Yu
- Center for Coronary Heart Disease, Department of Cardiology, Fu Wai Hospital, National Center for Cardiovascular Diseases of China, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Zhi-Feng Song
- Center for Coronary Heart Disease, Department of Cardiology, Fu Wai Hospital, National Center for Cardiovascular Diseases of China, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Zhi-Yao Wei
- Center for Coronary Heart Disease, Department of Cardiology, Fu Wai Hospital, National Center for Cardiovascular Diseases of China, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Ji Huang
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, National Clinical Research Center for Cardiovascular Diseases, Beijing, People’s Republic of China
| | - Hai-Yan Qian
- Center for Coronary Heart Disease, Department of Cardiology, Fu Wai Hospital, National Center for Cardiovascular Diseases of China, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
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Tan F, Li X, Wang Z, Li J, Shahzad K, Zheng J. Clinical applications of stem cell-derived exosomes. Signal Transduct Target Ther 2024; 9:17. [PMID: 38212307 PMCID: PMC10784577 DOI: 10.1038/s41392-023-01704-0] [Citation(s) in RCA: 178] [Impact Index Per Article: 178.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 10/15/2023] [Accepted: 11/12/2023] [Indexed: 01/13/2024] Open
Abstract
Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery, it nevertheless comes with inescapable drawbacks that might limit its clinical translation. Compared to stem cells, stem cell-derived exosomes possess numerous advantages, such as non-immunogenicity, non-infusion toxicity, easy access, effortless preservation, and freedom from tumorigenic potential and ethical issues. Exosomes can inherit similar therapeutic effects from their parental cells such as embryonic stem cells and adult stem cells through vertical delivery of their pluripotency or multipotency. After a thorough search and meticulous dissection of relevant literature from the last five years, we present this comprehensive, up-to-date, specialty-specific and disease-oriented review to highlight the surgical application and potential of stem cell-derived exosomes. Exosomes derived from stem cells (e.g., embryonic, induced pluripotent, hematopoietic, mesenchymal, neural, and endothelial stem cells) are capable of treating numerous diseases encountered in orthopedic surgery, neurosurgery, plastic surgery, general surgery, cardiothoracic surgery, urology, head and neck surgery, ophthalmology, and obstetrics and gynecology. The diverse therapeutic effects of stem cells-derived exosomes are a hierarchical translation through tissue-specific responses, and cell-specific molecular signaling pathways. In this review, we highlight stem cell-derived exosomes as a viable and potent alternative to stem cell-based therapy in managing various surgical conditions. We recommend that future research combines wisdoms from surgeons, nanomedicine practitioners, and stem cell researchers in this relevant and intriguing research area.
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Affiliation(s)
- Fei Tan
- Department of ORL-HNS, Shanghai Fourth People's Hospital, and School of Medicine, Tongji University, Shanghai, China.
- Plasma Medicine and Surgical Implants Center, Tongji University, Shanghai, China.
- The Royal College of Surgeons in Ireland, Dublin, Ireland.
- The Royal College of Surgeons of England, London, UK.
| | - Xuran Li
- Department of ORL-HNS, Shanghai Fourth People's Hospital, and School of Medicine, Tongji University, Shanghai, China
- Plasma Medicine and Surgical Implants Center, Tongji University, Shanghai, China
| | - Zhao Wang
- Department of ORL-HNS, Shanghai Fourth People's Hospital, and School of Medicine, Tongji University, Shanghai, China
| | - Jiaojiao Li
- Department of ORL-HNS, Shanghai Fourth People's Hospital, and School of Medicine, Tongji University, Shanghai, China
- Plasma Medicine and Surgical Implants Center, Tongji University, Shanghai, China
| | - Khawar Shahzad
- Department of ORL-HNS, Shanghai Fourth People's Hospital, and School of Medicine, Tongji University, Shanghai, China
- Plasma Medicine and Surgical Implants Center, Tongji University, Shanghai, China
| | - Jialin Zheng
- Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China
- Shanghai Frontiers Science Center of Nanocatalytic Medicine, Tongji University, Shanghai, China
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Correia M, Lopes J, Lopes D, Melero A, Makvandi P, Veiga F, Coelho JFJ, Fonseca AC, Paiva-Santos AC. Nanotechnology-based techniques for hair follicle regeneration. Biomaterials 2023; 302:122348. [PMID: 37866013 DOI: 10.1016/j.biomaterials.2023.122348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 09/26/2023] [Accepted: 10/05/2023] [Indexed: 10/24/2023]
Abstract
The hair follicle (HF) is a multicellular complex structure of the skin that contains a reservoir of multipotent stem cells. Traditional hair repair methods such as drug therapies, hair transplantation, and stem cell therapy have limitations. Advances in nanotechnology offer new approaches for HF regeneration, including controlled drug release and HF-specific targeting. Until recently, embryogenesis was thought to be the only mechanism for forming hair follicles. However, in recent years, the phenomenon of wound-induced hair neogenesis (WIHN) or de novo HF regeneration has gained attention as it can occur under certain conditions in wound beds. This review covers HF-specific targeting strategies, with particular emphasis on currently used nanotechnology-based strategies for both hair loss-related diseases and HF regeneration. HF regeneration is discussed in several modalities: modulation of the hair cycle, stimulation of progenitor cells and signaling pathways, tissue engineering, WIHN, and gene therapy. The HF has been identified as an ideal target for nanotechnology-based strategies for hair regeneration. However, some regulatory challenges may delay the development of HF regeneration nanotechnology based-strategies, which will be lastly discussed.
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Affiliation(s)
- Mafalda Correia
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - Joana Lopes
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - Daniela Lopes
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - Ana Melero
- Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia (Campus de Burjassot), Av. Vicente A. Estelles s/n, 46100, Burjassot, Valencia, Spain
| | - Pooyan Makvandi
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, 324000, Quzhou, Zhejiang, China
| | - Francisco Veiga
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - Jorge F J Coelho
- CEMMPRE - Department of Chemical Engineering, University of Coimbra, 3030-790, Coimbra, Portugal
| | - Ana C Fonseca
- CEMMPRE - Department of Chemical Engineering, University of Coimbra, 3030-790, Coimbra, Portugal.
| | - Ana Cláudia Paiva-Santos
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal.
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Sun M, Yang J, Fan Y, Zhang Y, Sun J, Hu M, Sun K, Zhang J. Beyond Extracellular Vesicles: Hybrid Membrane Nanovesicles as Emerging Advanced Tools for Biomedical Applications. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2303617. [PMID: 37749882 PMCID: PMC10646251 DOI: 10.1002/advs.202303617] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 08/02/2023] [Indexed: 09/27/2023]
Abstract
Extracellular vesicles (EVs), involved in essential physiological and pathological processes of the organism, have emerged as powerful tools for disease treatment owing to their unique natural biological characteristics and artificially acquired advantages. However, the limited targeting ability, insufficient production yield, and low drug-loading capability of natural simplex EVs have greatly hindered their development in clinical translation. Therefore, the establishment of multifunctional hybrid membrane nanovesicles (HMNVs) with favorable adaptability and flexibility has become the key to expanding the practical application of EVs. This timely review summarizes the current progress of HMNVs for biomedical applications. Different HMNVs preparation strategies including physical, chemical, and chimera approaches are first discussed. This review then individually describes the diverse types of HMNVs based on homologous or heterologous cell membrane substances, a fusion of cell membrane and liposome, as well as a fusion of cell membrane and bacterial membrane. Subsequently, a specific emphasis is placed on the highlight of biological applications of the HMNVs toward various diseases with representative examples. Finally, ongoing challenges and prospects of the currently developed HMNVs in clinical translational applications are briefly presented. This review will not only stimulate broad interest among researchers from diverse disciplines but also provide valuable insights for the development of promising nanoplatforms in precision medicine.
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Affiliation(s)
- Meng Sun
- Key Laboratory of Molecular Medicine and BiotherapySchool of Life SciencesBeijing Institute of TechnologyBeijing100081P. R. China
| | - Jiani Yang
- Key Laboratory of Molecular Medicine and BiotherapySchool of Life SciencesBeijing Institute of TechnologyBeijing100081P. R. China
| | - Yueyun Fan
- Key Laboratory of Molecular Medicine and BiotherapySchool of Life SciencesBeijing Institute of TechnologyBeijing100081P. R. China
| | - Yinfeng Zhang
- International Medical CenterBeijing Friendship HospitalCapital Medical UniversityBeijing100050P. R. China
| | - Jian Sun
- Department of Hepatobiliary SurgeryJinan University First Affiliated HospitalGuangzhou510630P. R. China
| | - Min Hu
- Department of Hepatobiliary SurgeryJinan University First Affiliated HospitalGuangzhou510630P. R. China
| | - Ke Sun
- Department of Urinary surgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China
| | - Jinfeng Zhang
- Key Laboratory of Molecular Medicine and BiotherapySchool of Life SciencesBeijing Institute of TechnologyBeijing100081P. R. China
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Wang L, Qiao S, Xia R, Liu Y, Hu Y, Wu Y, Zhou J, Liang G, Tian T, Cao L. Mesenchymal stromal cell-derived magnetic nanovesicles for enhanced skin retention and hair follicle growth. Cytotherapy 2023; 25:1176-1185. [PMID: 37516947 DOI: 10.1016/j.jcyt.2023.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 06/29/2023] [Accepted: 07/05/2023] [Indexed: 07/31/2023]
Abstract
BACKGROUND AIMS Extracellular vesicles and exosome-mimetic nanovesicles (NVs) derived from mesenchymal stromal cells (MSCs) have emerged as promising to promote hair growth. However, short local skin retention after subcutaneous administration hinders their clinical applications. METHODS In this study, we prepared magnetic nanovesicles (MNVs) from iron oxide nanoparticle-incorporated MSCs. MNVs contained more therapeutic growth factors than NVs derived from naive MSCs, and their localization and internalization were manipulated by external magnetic field. RESULTS Following the subcutaneous injection of MNVs into a mouse model of depilation-induced hair regeneration, the magnetic attraction increased their skin retention. Then, the cellular proliferation and β-catenin signaling in hair follicles (HF) were markedly enhanced by MNV injection and magnetic field application. Furthermore, an acceleration of HF growth was revealed by histological analysis. CONCLUSIONS The proposed strategy can enhance the therapeutic potential of MSC-derived NVs for hair regeneration and other dermatological diseases.
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Affiliation(s)
- Lei Wang
- Department of Dermatology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China
| | - Shuya Qiao
- Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Rushan Xia
- Department of Dermatology, Jiangnan University Medical Center, Wuxi, Jiangsu, China
| | - Yiwen Liu
- Department of Dermatology, Jiangnan University Medical Center, Wuxi, Jiangsu, China
| | - Yifei Hu
- Department of Dermatology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China
| | - Yajuan Wu
- Department of Dermatology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China
| | - Junhao Zhou
- Department of Dermatology, Jiangnan University Medical Center, Wuxi, Jiangsu, China
| | - Gaofeng Liang
- School of Basic Medical Sciences, Henan University of Science & Technology, Luoyang, Henan, China
| | - Tian Tian
- Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Lei Cao
- Department of Dermatology, Jiangnan University Medical Center, Wuxi, Jiangsu, China.
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Kang MS, Park TE, Jo HJ, Kang MS, Lee SB, Hong SW, Kim KS, Han DW. Recent Trends in Macromolecule-Based Approaches for Hair Loss Treatment. Macromol Biosci 2023; 23:e2300148. [PMID: 37245081 DOI: 10.1002/mabi.202300148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/21/2023] [Indexed: 05/29/2023]
Abstract
Macromolecules are large, complex molecules composed of smaller subunits known as monomers. The four primary categories of macromolecules found in living organisms are carbohydrates, lipids, proteins, and nucleic acids; they also encompass a broad range of natural and synthetic polymers. Recent studies have shown that biologically active macromolecules can help regenerate hair, providing a potential solution for current hair regeneration therapies. This review examines the latest developments in the use of macromolecules for the treatment of hair loss. The fundamental principles of hair follicle (HF) morphogenesis, hair shaft (HS) development, hair cycle regulation, and alopecia have been introduced. Microneedle (MN) and nanoparticle (NP) delivery systems are innovative treatments for hair loss. Additionally, the application of macromolecule-based tissue-engineered scaffolds for the in vitro and in vivo neogenesis of HFs is discussed. Furthermore, a new research direction is explored wherein artificial skin platforms are adopted as a promising screening method for hair loss treatment drugs. Through these multifaceted approaches, promising aspects of macromolecules for future hair loss treatments are identified.
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Affiliation(s)
- Moon Sung Kang
- Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, 46241, Republic of Korea
| | - Tae Eon Park
- School of Chemical Engineering, Pusan National University, Busan, 46241, Republic of Korea
| | - Hyo Jung Jo
- Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, 46241, Republic of Korea
| | - Min Seok Kang
- School of Chemical Engineering, Pusan National University, Busan, 46241, Republic of Korea
| | - Su Bin Lee
- School of Chemical Engineering, Pusan National University, Busan, 46241, Republic of Korea
| | - Suck Won Hong
- Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, 46241, Republic of Korea
- Engineering Research Center for Color-Modulated Extra-Sensory Perception Technology, Pusan National University, Busan, 46241, Republic of Korea
| | - Ki Su Kim
- School of Chemical Engineering, Pusan National University, Busan, 46241, Republic of Korea
- Institute of Advanced Organic Materials, Pusan National University, Busan, 46241, Republic of Korea
| | - Dong-Wook Han
- Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, 46241, Republic of Korea
- BIO-IT Fusion Technology Research Institute, Pusan National University, Busan, 46241, Republic of Korea
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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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Liang X, Li C, Song J, Liu A, Wang C, Wang W, Kang Y, Sun D, Qian J, Zhang X. HucMSC-Exo Promote Mucosal Healing in Experimental Colitis by Accelerating Intestinal Stem Cells and Epithelium Regeneration via Wnt Signaling Pathway. Int J Nanomedicine 2023; 18:2799-2818. [PMID: 37256205 PMCID: PMC10226545 DOI: 10.2147/ijn.s402179] [Citation(s) in RCA: 12] [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: 01/31/2023] [Accepted: 05/19/2023] [Indexed: 06/01/2023] Open
Abstract
BACKGROUND Mucosal healing has emerged as a crucial therapeutic goal for inflammatory bowel diseases (IBD). Exosomes (Exo) as a potential acellular candidate for stem cell therapy might be competent to promote mucosal healing, while its mechanism remains unexplored. METHODS Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) were subjected to experimental colitis mice intraperitoneally to estimate the role in mucosal healing and the regeneration of intestinal stem cells (ISCs) and epithelium. The intestinal organoid model of IBD was constructed utilizing tumor necrosis factor (TNF)-α for subsequent function analysis in vitro. Transcriptome sequencing was performed to decipher the underlying mechanism and Wnt-C59, an oral Wnt inhibitor, was used to confirm that further. Finally, the potential specific components of hucMSC‑exo were investigated based on several existing miRNA expression datasets. RESULTS HucMSC-exo showed striking potential for mucosal healing in colitis mice, characterized by decreased histopathological injuries and neutrophil infiltration as well as improved epithelial integrity. HucMSC-exo up-regulated the expression of leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a specific marker for ISCs and accelerated the proliferation of intestinal epithelium. HucMSC-exo endowed intestinal organoids with more excellent capacity to grow and bud under TNF-α stimulation. More than that, the fact that hucMSC-exo activated the canonical Wnt signaling pathway to promote mucosal healing was uncovered by not only RNA-sequencing but also relevant experimental data. Finally, bioinformatics analysis of the existing miRNA expression datasets indicated that several miRNAs abundant in hucMSC-exo involved widely in regeneration or repair related biological processes and Wnt signaling pathway might be one of the most important signal transduction pathways. CONCLUSION Our results suggested that hucMSC-exo could facilitate mucosal healing in experimental colitis by accelerating ISCs and intestinal epithelium regeneration via transferring key miRNAs, which was dependent on the activation of Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Xiaonan Liang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, People’s Republic of China
| | - Chenyang Li
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, People’s Republic of China
| | - Jia Song
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, People’s Republic of China
| | - Airu Liu
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, People’s Republic of China
| | - Chen Wang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, People’s Republic of China
| | - Wenxin Wang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, People’s Republic of China
| | - Yaxing Kang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, People’s Republic of China
- Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China
| | - Donglei Sun
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, People’s Republic of China
| | - Jiaming Qian
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, People’s Republic of China
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Xiaolan Zhang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, People’s Republic of China
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Rong Y, Wang Z, Tang P, Wang J, Ji C, Chang J, Zhu Y, Ye W, Bai J, Liu W, Yin G, Yu L, Zhou X, Cai W. Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury. Bioact Mater 2023; 23:328-342. [PMID: 36474657 PMCID: PMC9706413 DOI: 10.1016/j.bioactmat.2022.11.011] [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: 04/25/2022] [Revised: 10/26/2022] [Accepted: 11/16/2022] [Indexed: 11/26/2022] Open
Abstract
Spinal cord injury (SCI) is a severe disease of the nervous system that causes irreparable damage and loss of function, for which no effective treatments are available to date. Engineered extracellular vesicles (EVs) carrying therapeutic molecules hold promise as an alternative SCI therapy depending on the specific functionalized EVs and the appropriate engineering strategy. In this study, we demonstrated the design of a drug delivery system of peptide CAQK-modified, siRNA-loaded EVs (C-EVs-siRNA) for SCI-targeted therapy. The peptide CAQK was anchored through a chemical modification to the membranes of EVs isolated from induced neural stem cells (iNSCs). CCL2-siRNA was then loaded into the EVs through electroporation. The modified EVs still maintained the basic properties of EVs and showed favorable targeting and therapeutic effects in vitro and in vivo. C-EVs-siRNA specifically delivered siRNA to the SCI region and was taken up by target cells. C-EVs-siRNA used the inherent anti-inflammatory and neuroreparative functions of iNSCs-derived EVs in synergy with the loaded siRNA, thus enhancing the therapeutic effect against SCI. The combination of targeted modified EVs and siRNA effectively regulated the microenvironmental disturbance after SCI, promoted the transformation of microglia/macrophages from M1 to M2 and limited the negative effects of the inflammatory response and neuronal injury on functional recovery in mice after SCI. Thus, engineered EVs are a potentially feasible and efficacious treatment for SCI, and may also be used to develop targeted treatments for other diseases.
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Affiliation(s)
- Yuluo Rong
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Zhuanghui Wang
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Pengyu Tang
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Jiaxing Wang
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Chengyue Ji
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Jie Chang
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Yufeng Zhu
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Wu Ye
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Jianling Bai
- Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Wei Liu
- Department of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China
| | - Guoyong Yin
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Lipeng Yu
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Xuhui Zhou
- Department of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China
- Department of Orthopedics, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, Shanghai, 200003, China
| | - Weihua Cai
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
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Zou W, Zhang J, Li Z, Zhou Y, Zhou S, Liu G. A novel therapeutic approach for allergic rhinitis by exosome-mimetic nanovesicles derived from mesenchymal stem cells to restore nasal mucosal epithelial barrier. Med Hypotheses 2023. [DOI: 10.1016/j.mehy.2023.111046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/13/2023]
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Fu H, Li W, Weng Z, Huang Z, Liu J, Mao Q, Ding B. Water extract of cacumen platycladi promotes hair growth through the Akt/GSK3β/β-catenin signaling pathway. Front Pharmacol 2023; 14:1038039. [PMID: 36891275 PMCID: PMC9986263 DOI: 10.3389/fphar.2023.1038039] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 02/09/2023] [Indexed: 02/22/2023] Open
Abstract
Cacumen Platycladi (CP) consists of the dried needles of Platycladus orientalis L.) Franco. It was clinically demonstrated that it effectively regenerates hair, but the underlying mechanism remains unknown. Thus, we employed shaved mice to verify the hair growth-promoting capability of the water extract of Cacumen Platycladi (WECP). The morphological and histological analyses revealed that WECP application could significantly promote hair growth and hair follicles (HFs) construction, in comparison to that of control group. Additionally, the skin thickness and hair bulb diameter were significantly increased by the application of WECP in a dose-dependent manner. Besides, the high dose of WECP also showed an effect similar to that of finasteride. In an in vitro assay, WECP stimulated dermal papilla cells (DPCs) proliferation and migration. Moreover, the upregulation of cyclins (cyclin D1, cyclin-dependent kinase 2 (CDK2), and cyclin-dependent kinase 4 (CDK4)) and downregulation of P21 in WECP-treated cell assays have been evaluated. We identified the ingredients of WECP using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) and endeavored to predict their relevant molecular mechanisms by network analysis. We found that the Akt (serine/threonine protein kinase) signaling pathway might be a crucial target of WECP. It has been demonstrated that WECP treatment activated the phosphorylation of Akt and glycogen synthase kinase-3-beta (GSK3β), promoted β-Catenin and Wnt10b accumulation, and upregulated the expression of lymphoid enhancer-binding factor 1 (LEF1), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF1). We also found that WECP significantly altered the expression levels of apoptosis-related genes in mouse dorsal skin. The enhancement capability of WECP on DPCs proliferation and migration could be abrogated by the Akt-specific inhibitor MK-2206 2HCl. These results suggested that WECP might promote hair growth by modulating DPCs proliferation and migration through the regulation of the Akt/GSK3β/β-Catenin signaling pathway.
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Affiliation(s)
- Hangjie Fu
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.,Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Wenxia Li
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhiwei Weng
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.,Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhiguang Huang
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.,Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jinyuan Liu
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.,Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qingqing Mao
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.,Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Bin Ding
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.,Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
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26
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Zhang B, Gong J, He L, Khan A, Xiong T, Shen H, Li Z. Exosomes based advancements for application in medical aesthetics. Front Bioeng Biotechnol 2022; 10:1083640. [PMID: 36605254 PMCID: PMC9810265 DOI: 10.3389/fbioe.2022.1083640] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 12/05/2022] [Indexed: 01/07/2023] Open
Abstract
Beauty is an eternal pursuit of all people. Wound repair, anti-aging, inhibiting hyperpigmentation and hair loss are the main demands for medical aesthetics. At present, the repair and remodeling of human body shape and function in medical aesthetics are often achieved by injection of antioxidants, hyaluronic acid and botulinum toxin, stem cell therapy. However, there are some challenges, such as difficulty controlling the injection dose, abnormal local contour, increased foreign body sensation, and the risk of tumor occurrence and deformity induced by stem cell therapy. Exosomes are tiny vesicles secreted by cells, which are rich in proteins, nucleic acids and other bioactive molecules. They have the characteristics of low immunogenicity and strong tissue penetration, making them ideal for applications in medical aesthetics. However, their low yield, strong heterogeneity, and long-term preservation still hinder their application in medical aesthetics. In this review, we summarize the mechanism of action, administration methods, engineered production and preservation technologies for exosomes in medical aesthetics in recent years to further promote their research and industrialization in the field of medical aesthetics.
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Affiliation(s)
- Bin Zhang
- College of Life Science, Yangtze University, Jingzhou, China
- Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Jianmin Gong
- College of Life Science, Yangtze University, Jingzhou, China
- Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Lei He
- Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Adeel Khan
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, Nanjing, China
| | - Tao Xiong
- College of Life Science, Yangtze University, Jingzhou, China
| | - Han Shen
- Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Zhiyang Li
- Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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27
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Rajendran RL, Gangadaran P, Kwack MH, Oh JM, Hong CM, Jeyaraman M, Sung YK, Lee J, Ahn BC. Engineered Nanovesicles from Fibroblasts Modulate Dermal Papillae Cells In Vitro and Promote Human Hair Follicle Growth Ex Vivo. Cells 2022; 11:4066. [PMID: 36552830 PMCID: PMC9777471 DOI: 10.3390/cells11244066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 11/27/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
Alopecia is a common medical condition affecting both sexes. Dermal papilla (DP) cells are the primary source of hair regeneration in alopecia patients. Therapeutic applications of extracellular vesicles (EVs) are restricted by low yields, high costs, and their time-consuming collection process. Thus, engineered nanovesicles (eNVs) have emerged as suitable therapeutic biomaterials in translational medicine. We isolated eNVs by the serial extrusion of fibroblasts (FBs) using polycarbonate membrane filters and serial and ultracentrifugation. We studied the internalization, proliferation, and migration of human DP cells in the presence and absence of FB-eNVs. The therapeutic potential of FB-eNVs was studied on ex vivo organ cultures of human hair follicles (HFs) from three human participants. FB-eNVs (2.5, 5, 7.5, and 10 µg/mL) significantly enhanced DP cell proliferation, with the maximum effect observed at 7.5 µg/mL. FB-eNVs (5 and 10 µg/mL) significantly enhanced the migration of DP cells at 36 h. Western blotting results suggested that FB-eNVs contain vascular endothelial growth factor (VEGF)-a. FB-eNV treatment increased the levels of PCNA, pAKT, pERK, and VEGF-receptor-2 (VEGFR2) in DP cells. Moreover, FB-eNVs increased the human HF shaft size in a short duration ex vivo. Altogether, FB-eNVs are promising therapeutic candidates for alopecia.
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Affiliation(s)
- Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Mi Hee Kwack
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Ji Min Oh
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Chae Moon Hong
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, Republic of Korea
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute University, Chennai 600056, Tamil Nadu, India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, Uttar Pradesh, India
| | - Young Kwan Sung
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Jaetae Lee
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, Republic of Korea
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, Republic of Korea
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28
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Li J, Zhao B, Dai Y, Zhang X, Chen Y, Wu X. Exosomes Derived from Dermal Papilla Cells Mediate Hair Follicle Stem Cell Proliferation through the Wnt3a/ β-Catenin Signaling Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:9042345. [PMID: 36388171 PMCID: PMC9663250 DOI: 10.1155/2022/9042345] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/25/2022] [Accepted: 10/14/2022] [Indexed: 08/18/2023]
Abstract
Both hair follicle stem cells (HFSC) and dermal papilla cells (DPC) are essential for hair follicle growth and proliferation. In this study, HFSCs and DPCs that made signature proteins like KRT14, KRT15, KRT19, α-SMA, and Versican were obtained. Cell coculture systems between HFSCs and DPCs were used to measure the increased PCNA protein content in HFSCs. Additionally, exosomes from dermal papilla cells (DPC-Exos), the overexpression and silencing of Wnt3a, could regulate the Wnt/β-catenin signaling pathway downstream genes. After collecting DPC-ExosOE-Wnt3a, the treatment of HFSC with DPC-ExosOE-Wnt3a showed that DPC-ExosOE-Wnt3a could upregulate the mRNA expression of downstream genes in the Wnt/β-catenin signaling pathway and that DPC-ExosOE-Wnt3a enhanced the proliferation of HFSCs while inhibiting their apoptosis. These findings suggest that DPC-Exos could regulate HFSC cell proliferation via the Wnt3a/β-catenin signaling pathway. This research offers novel concepts for the molecular breeding and efficient production of Angora rabbits, as well as for the treatment of human hair problems.
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Affiliation(s)
- Jiali Li
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
| | - Bohao Zhao
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
- Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yingying Dai
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
| | - Xiyu Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yang Chen
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
- Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou, Jiangsu, China
| | - Xinsheng Wu
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
- Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou, Jiangsu, China
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29
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Du Y, Wang H, Yang Y, Zhang J, Huang Y, Fan S, Gu C, Shangguan L, Lin X. Extracellular Vesicle Mimetics: Preparation from Top-Down Approaches and Biological Functions. Adv Healthc Mater 2022; 11:e2200142. [PMID: 35899756 DOI: 10.1002/adhm.202200142] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 07/15/2022] [Indexed: 01/27/2023]
Abstract
Extracellular vesicles (EVs) have attracted attention as delivery vehicles due to their structure, composition, and unique properties in regeneration and immunomodulation. However, difficulties during production and isolation processes of EVs limit their large-scale clinical applications. EV mimetics (EVMs), prepared via top-down strategies that improve the yield of nanoparticles while retaining biological properties similar to those of EVs have been used to address these limitations. Herein, the preparation of EVMs is reviewed and their characteristics in terms of structure, composition, targeting ability, cellular uptake mechanism, and immunogenicity, as well as their strengths, limitations, and future clinical application prospects as EV alternatives are summarized.
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Affiliation(s)
- Yuan Du
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310020, China.,Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Hongyi Wang
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310020, China.,Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Yang Yang
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310020, China.,Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Jianfeng Zhang
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310020, China
| | - Yue Huang
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310020, China
| | - Shunwu Fan
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310020, China.,Hangzhou OrigO Biotechnology Co. Ltd., Hangzhou, 311200, China
| | - Chenhui Gu
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310020, China.,Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.,Hangzhou OrigO Biotechnology Co. Ltd., Hangzhou, 311200, China
| | - Liqing Shangguan
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310020, China.,Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Xianfeng Lin
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310020, China.,Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.,Hangzhou OrigO Biotechnology Co. Ltd., Hangzhou, 311200, China
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30
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Sheng X, Wang S, Huang M, Fan K, Wang J, Lu Q. Bioinformatics Analysis of the Key Genes and Pathways in Multiple Myeloma. Int J Gen Med 2022; 15:6999-7016. [PMID: 36090706 PMCID: PMC9462443 DOI: 10.2147/ijgm.s377321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 08/19/2022] [Indexed: 11/23/2022] Open
Abstract
Objective To study the differentially expressed genes between multiple myeloma and healthy whole blood samples by bioinformatics analysis, find out the key genes involved in the occurrence, development and prognosis of multiple myeloma, and analyze and predict their functions. Methods The gene chip data GSE146649 was downloaded from the GEO expression database. The gene chip data GSE146649 was analyzed by R language to obtain the genes with different expression in multiple myeloma and healthy samples, and the cluster analysis heat map was constructed. At the same time, the protein-protein interaction (PPI) networks of these DEGs were established by STRING and Cytoscape software. The gene co-expression module was constructed by weighted correlation network analysis (WGCNA). The hub genes were identified from key gene and central gene. TCGA database was used to analyze the expression of differentially expressed genes in patients with multiple myeloma. Finally, the expression level of TNFSF11 in whole blood samples from patients with multiple myeloma was analyzed by RT qPCR. Results We identified four genes (TNFSF11, FGF2, SGMS2, IGFBP7) as hub genes of multiple myeloma. Then, TCGA database was used to analyze the survival of TNFSF11, FGF2, SGMS2 and IGFBP7 in patients with multiple myeloma. Finally, the expression level of TNFSF11 in whole blood samples from patients with multiple myeloma was analyzed by RT qPCR. Conclusion The study suggests that TNFSF11, FGF2, SGMS2 and IGFBP7 are important research targets to explore the pathogenesis, diagnosis and treatment of multiple myeloma.
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Affiliation(s)
- Xinge Sheng
- Department of Hematology, Zhongshan Hospital Xiamen University, Xiamen, People’s Republic of China
- Clinical Medicine Department, School of Medicine, Xiamen University, Xiamen, People’s Republic of China
| | - Shuo Wang
- Clinical Medicine Department, School of Medicine, Xiamen University, Xiamen, People’s Republic of China
| | - Meijiao Huang
- Department of Hematology, Zhongshan Hospital Xiamen University, Xiamen, People’s Republic of China
| | - Kaiwen Fan
- Department of Hematology, Zhongshan Hospital Xiamen University, Xiamen, People’s Republic of China
- Clinical Medicine Department, School of Medicine, Xiamen University, Xiamen, People’s Republic of China
| | - Jiaqi Wang
- Department of Hematology, Zhongshan Hospital Xiamen University, Xiamen, People’s Republic of China
- Clinical Medicine Department, School of Medicine, Xiamen University, Xiamen, People’s Republic of China
| | - Quanyi Lu
- Department of Hematology, Zhongshan Hospital Xiamen University, Xiamen, People’s Republic of China
- Clinical Medicine Department, School of Medicine, Xiamen University, Xiamen, People’s Republic of China
- Correspondence: Quanyi Lu, Tel +86 13600959425, Email
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31
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Kim HY, Kwon S, Um W, Shin S, Kim CH, Park JH, Kim BS. Functional Extracellular Vesicles for Regenerative Medicine. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2106569. [PMID: 35322545 DOI: 10.1002/smll.202106569] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 02/22/2022] [Indexed: 06/14/2023]
Abstract
The unique biological characteristics and promising clinical potential of extracellular vesicles (EVs) have galvanized EV applications for regenerative medicine. Recognized as important mediators of intercellular communication, naturally secreted EVs have the potential, as innate biotherapeutics, to promote tissue regeneration. Although EVs have emerged as novel therapeutic agents, challenges related to the clinical transition have led to further functionalization. In recent years, various engineering approaches such as preconditioning, drug loading, and surface modification have been developed to potentiate the therapeutic outcomes of EVs. Also, limitations of natural EVs have been addressed by the development of artificial EVs that offer advantages in terms of production yield and isolation methodologies. In this review, an updated overview of current techniques is provided for the functionalization of natural EVs and recent advances in artificial EVs, particularly in the scope of regenerative medicine.
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Affiliation(s)
- Han Young Kim
- Department of Biomedical-Chemical Engineering, The Catholic University of Korea, Bucheon, 14662, Republic of Korea
| | - Seunglee Kwon
- School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Wooram Um
- School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Sol Shin
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Republic of Korea
| | - Chan Ho Kim
- School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Jae Hyung Park
- School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Republic of Korea
- Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Byung-Soo Kim
- School of Chemical and Biological Engineering, Interdisciplinary Program of Bioengineering, Institute of Chemical Processes, Institute of Engineering Research, BioMAX, Seoul National University, Seoul, 08826, Republic of Korea
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32
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Rajendran RL, Gangadaran P, Kwack MH, Oh JM, Hong CM, Sung YK, Lee J, Ahn BC. Application of extracellular vesicles from mesenchymal stem cells promotes hair growth by regulating human dermal cells and follicles. World J Stem Cells 2022; 14:527-538. [PMID: 36157528 PMCID: PMC9350621 DOI: 10.4252/wjsc.v14.i7.527] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 05/19/2022] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Dermal papillae (DP) and outer root sheath (ORS) cells play important roles in hair growth and regeneration by regulating the activity of hair follicle (HF) cells. AIM To investigate the effects of human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) on DP and ORS cells as well as HFs. EVs are known to regulate various cellular functions. However, the effects of hMSC-EVs on hair growth, particularly on human-derived HF cells (DP and ORS cells), and the possible mechanisms underlying these effects are unknown. METHODS hMSC-EVs were isolated and characterized using transmission electron micro scopy, nanoparticle tracking analysis, western blotting, and flow cytometry. The activation of DP and ORS cells was analyzed using cellular proliferation, migration, western blotting, and real-time polymerase chain reaction. HF growth was evaluated ex vivo using human HFs. RESULTS Wnt3a is present in a class of hMSC-EVs and associated with the EV membrane. hMSC-EVs promote the proliferation of DP and ORS cells. Moreover, they translocate β-catenin into the nucleus of DP cells by increasing the expression of β-catenin target transcription factors (Axin2, EP2 and LEF1) in DP cells. Treatment with hMSC-EVs also promoted the migration of ORS cells and enhanced the expression of keratin (K) differentiation markers (K6, K16, K17, and K75) in ORS cells. Furthermore, treatment with hMSC-EVs increases hair shaft elongation in cultured human HFs. CONCLUSION These findings suggest that hMSC-EVs are potential candidates for further preclinical and clinical studies on hair loss treatment.
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Affiliation(s)
- Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Mi Hee Kwack
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Ji Min Oh
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Chae Moon Hong
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea
| | - Young Kwan Sung
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Jaetae Lee
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea.
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33
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Gangadaran P, Rajendran RL, Kwack MH, Jeyaraman M, Hong CM, Sung YK, Ahn BC. Application of Cell-Derived Extracellular Vesicles and Engineered Nanovesicles for Hair Growth: From Mechanisms to Therapeutics. Front Cell Dev Biol 2022; 10:963278. [PMID: 35912106 PMCID: PMC9329781 DOI: 10.3389/fcell.2022.963278] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 06/24/2022] [Indexed: 11/16/2022] Open
Abstract
Hair loss is one of the most common disorders that affect both male and female patients. Cell-derived nanovesicles (CDVs) are natural extracellular vesicles and engineered nanovesicles that can carry various biologicals materials such as proteins, lipids, mRNA, miRNA, and DNA. These vesicles can communicate with local or distant cells and are capable of delivering endogenous materials and exogenous drugs for regenerative therapies. Recent studies revealed that CDVs can serve as new treatment strategies for hair growth. Herein, we review current knowledge on the role of CDVs in applications to hair growth. The in-depth understanding of the mechanisms by which CDVs enable therapeutic effects for hair growth may accelerate successful clinical translation of these vesicles for treating hair loss.
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Affiliation(s)
- Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Mi Hee Kwack
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu, South Korea
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Madhan Jeyaraman
- Department of Orthopaedics, Faculty of Medicine, Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Noida, India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, India
| | - Chae Moon Hong
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Young Kwan Sung
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu, South Korea
- Department of Immunology, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu, South Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea
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Kazi T, Nagata A, Nakagawa T, Matsuzaki T, Inui S. Dermal Papilla Cell-Derived Extracellular Vesicles Increase Hair Inductive Gene Expression in Adipose Stem Cells via β-Catenin Activation. Cells 2022; 11:202. [PMID: 35053317 PMCID: PMC8773911 DOI: 10.3390/cells11020202] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 01/02/2022] [Accepted: 01/04/2022] [Indexed: 01/06/2023] Open
Abstract
Recently, extracellular vesicle (EV)-mediated cell differentiation has gained attention in developmental biology due to genetic exchange between donor cells and recipient cells via transfer of mRNA and miRNA. EVs, also known as exosomes, play a role in maintaining paracrine cell communication and can induce cell proliferation and differentiation. However, it remains unclear whether adipose-derived stem cells (ASCs) can adopt dermal papilla (DP)-like properties with dermal papilla cell-derived extracellular vesicles (DPC-EVs). To understand the effect of DPC-EVs on cell differentiation, DPC-EVs were characterized and incubated with ASCs, of monolayer and spheroid cell cultures, in combination with the CAO1/2FP medium specialized for dermal papilla cells (DPCs). DPC-like properties in ASCs were initially evaluated by comparing several genes and proteins with those of DPCs via real-time PCR analysis and immunostaining, respectively. We also evaluated the presence of hair growth-related microRNAs (miRNAs), specifically mir-214-5P, mir-218-5p, and mir-195-5P. Here, we found that miRNA expression patterns varied in DPC-EVs from passage 4 (P4) or P5. In addition, DPC-EVs in combination with CAP1/2FP accelerated ASC proliferation at low concentrations and propagated hair inductive gene expression for versican (vcan), alpha-smooth muscle actin (α-sma), osteopontin (opn), and N-Cam (ncam). Comparison between the expression of hair inductive genes (vcan, α-sma, ctnb, and others), the protein VCAN, α-SMA and β-Catenin (CTNB), and hair inductive miRNAs (mir-214-5P, mir-218-5p, and mir-195-5p) of DPC-EVs revealed similarities between P4 DPC-EVs-treated ASCs and DPCs. We concluded that early passage DPC-EVs, in combination with CAP1/2FP, enabled ASCs to transdifferentiate into DPC-like cells.
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Affiliation(s)
- Taheruzzaman Kazi
- Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (A.N.); (T.N.); (S.I.)
| | - Abir Nagata
- Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (A.N.); (T.N.); (S.I.)
| | - Takatoshi Nakagawa
- Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (A.N.); (T.N.); (S.I.)
| | - Takashi Matsuzaki
- Department of Biological Science, Faculty of Life and Environment Science, Shimane University, Shimane 690-0823, Japan
| | - Shigeki Inui
- Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (A.N.); (T.N.); (S.I.)
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35
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Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct Target Ther 2022; 7:3. [PMID: 34980884 PMCID: PMC8724284 DOI: 10.1038/s41392-021-00762-6] [Citation(s) in RCA: 1106] [Impact Index Per Article: 368.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/28/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
The Wnt/β-catenin pathway comprises a family of proteins that play critical roles in embryonic development and adult tissue homeostasis. The deregulation of Wnt/β-catenin signalling often leads to various serious diseases, including cancer and non-cancer diseases. Although many articles have reviewed Wnt/β-catenin from various aspects, a systematic review encompassing the origin, composition, function, and clinical trials of the Wnt/β-catenin signalling pathway in tumour and diseases is lacking. In this article, we comprehensively review the Wnt/β-catenin pathway from the above five aspects in combination with the latest research. Finally, we propose challenges and opportunities for the development of small-molecular compounds targeting the Wnt signalling pathway in disease treatment.
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36
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Villarreal-Leal RA, Healey GD, Corradetti B. Biomimetic immunomodulation strategies for effective tissue repair and restoration. Adv Drug Deliv Rev 2021; 179:113913. [PMID: 34371087 DOI: 10.1016/j.addr.2021.113913] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 07/21/2021] [Accepted: 07/30/2021] [Indexed: 12/12/2022]
Abstract
Inflammation plays a central role in wound healing following injury or disease and is mediated by a precise cascade of cellular and molecular events. Unresolved inflammatory processes lead to chronic inflammation and fibrosis, which can result in prolonged wound healing lasting months or years that hampers tissue function. Therapeutic interventions mediated by immunomodulatory drugs, cells, or biomaterials, are therefore most effective during the inflammatory phase of wound healing when a pro-regenerative environment is essential. In this review, we discuss the advantages of exploiting knowledge of the native tissue microenvironment to develop therapeutics capable of modulating the immune response and promoting functional tissue repair. In particular, we provide examples of the most recent biomimetic platforms proposed to accomplish this goal, with an emphasis on those able to induce macrophage polarization towards a pro-regenerative phenotype.
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37
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Rajendran RL, Gangadaran P, Kwack MH, Oh JM, Hong CM, Gopal A, Sung YK, Lee J, Ahn BC. Engineered extracellular vesicle mimetics from macrophage promotes hair growth in mice and promotes human hair follicle growth. Exp Cell Res 2021; 409:112887. [PMID: 34678305 DOI: 10.1016/j.yexcr.2021.112887] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 10/15/2021] [Accepted: 10/18/2021] [Indexed: 12/14/2022]
Abstract
Recent studies clearly show that cell-derived extracellular vesicles (EVs, including exosomes) can promote hair growth. However, large-scale production of EVs remains a big hurdle. Recently, extracellular vesicle mimetics (EMs) engineered by extrusion through various membranes are emerging as a complementary approach for large-scale production. In this study, to investigate their ability to induce hair growth, we generated macrophage-engineered EMs (MAC-EMs) that activated the human dermal papilla (DP) cells in vitro. MAC-EMs intradermally injected into the skin of C57BL/6 mice were retained for up to 72 h. Microscopy imaging revealed that MAC-EMs were predominately internalized into hair follicles. The MAC-EMs treatment induced hair regrowth in mice and hair shaft elongation in a human hair follicle, suggesting the potential of MAC-EMs as an alternative to EVs to overcome clinical limitation.
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Affiliation(s)
- Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Mi Hee Kwack
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Ji Min Oh
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Chae Moon Hong
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Arunnehru Gopal
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Young Kwan Sung
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Jaetae Lee
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.
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38
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Li Y, Xiao Q, Tang J, Xiong L, Li L. Extracellular Vesicles: Emerging Therapeutics in Cutaneous Lesions. Int J Nanomedicine 2021; 16:6183-6202. [PMID: 34522095 PMCID: PMC8434831 DOI: 10.2147/ijn.s322356] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 08/17/2021] [Indexed: 02/05/2023] Open
Abstract
Extracellular vesicles (EVs), as nanoscale membranous vesicles containing DNAs, RNAs, lipids and proteins, have emerged as promising diagnostic and therapeutic agents for skin diseases. Here, we summarize the basic physiology of the skin and the biological characteristic of EVs. Further, we describe the applications of EVs in the treatment of dermatological conditions such as skin infection, inflammatory skin diseases, skin repair and rejuvenation and skin cancer. In particular, plant-derived EVs and clinical trials are discussed. In addition, challenges and perspectives related to the preclinical and clinical applications of EVs are highlighted.
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Affiliation(s)
- Yu Li
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,Cosmetics Safety and Efficacy Evaluation Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,NMPA Key Laboratory for Human Evaluation and Big Data of Cosmetics, Chengdu, 610041, People's Republic of China
| | - Qing Xiao
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,Cosmetics Safety and Efficacy Evaluation Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,NMPA Key Laboratory for Human Evaluation and Big Data of Cosmetics, Chengdu, 610041, People's Republic of China
| | - Jie Tang
- Cosmetics Safety and Efficacy Evaluation Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,NMPA Key Laboratory for Human Evaluation and Big Data of Cosmetics, Chengdu, 610041, People's Republic of China.,Sichuan Engineering Technology Research Center of Cosmetic, Chengdu, 610041, People's Republic of China
| | - Lidan Xiong
- Cosmetics Safety and Efficacy Evaluation Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,NMPA Key Laboratory for Human Evaluation and Big Data of Cosmetics, Chengdu, 610041, People's Republic of China.,Sichuan Engineering Technology Research Center of Cosmetic, Chengdu, 610041, People's Republic of China
| | - Li Li
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,Cosmetics Safety and Efficacy Evaluation Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,NMPA Key Laboratory for Human Evaluation and Big Data of Cosmetics, Chengdu, 610041, People's Republic of China.,Sichuan Engineering Technology Research Center of Cosmetic, Chengdu, 610041, People's Republic of China
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