Epidermal stem cell-derived exosomes promote skin regeneration by downregulating transforming growth factor-β1 in wound healing

Stem Cell Research & Therapy

Yupeng Meng¹  Yan Zhang¹  Ming Qian¹  Haiyang Zhang¹  Mengna Duan²  Guokun Zhang³ 

[1] Department of Prosthodontics, Hospital of Stomatology, Jilin University, 1500 Qinghua Rd., 130021, Changchun, Jilin, China;Department of Prosthodontics, Hospital of Stomatology, Jilin University, 1500 Qinghua Rd., 130021, Changchun, Jilin, China;Jilin Provincial Laboratory of Biomedical Engineering, Jilin University, 1500 Qinghua Rd., 130021, Changchun, Jilin, China;Institute of Antler Science and Product Technology, Changchun Sci-Tech University, 1345 Pudong Rd., 130600, Changchun, Jilin, China;Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences (CAAS), 4899 Juye St., 130112, Changchun, Jilin, China;

关键词: Exosome;    Epidermal stem cells;    MicroRNA;    Myofibroblast;    Transforming growth factor-β1;   

DOI  :  10.1186/s13287-020-01971-6

来源: Springer

【 摘 要 】

BackgroundScar formation, which may be caused by myofibroblast aggregations, is the greatest challenge during skin wound healing in the clinical setting. Studies have indicated that epidermal stem cells (EPSC) improve wound healing and reduce scar formation.MethodsWe investigated the therapeutic effects of EPSC-derived exosomes (EPSC-Exos) on skin wound healing in a skin-defect rat model. We also examined the roles of EPSC-Exos-specific microRNAs in inhibiting the differentiation of human dermal fibroblasts (HDF) into myofibroblasts.ResultsWe found that EPSC-Exos increased the wound healing rate and reduced scar formation in rats. Also, EPSC-Exos improved the regeneration levels of skin appendages, nerves and vessels, as well as the natural distribution of collagen. Furthermore, we found these functions may be achieved by inhibiting the activity of transforming growth factor-β1 (TGF-β1) and its downstream genes. The results showed that some specific microRNAs, including miR-16, let-7a, miR-425-5p and miR-142-3p, were enriched in EPSC-Exos. EPSC-Exos-specific microRNAs, especially miR-425-5p and miR-142-3p, played vital roles in inhibiting myofibroblast differentiation via reducing the TGF-β1 expression in dermal fibroblasts.ConclusionWe found a novel function of EPSC-Exos-specific microRNAs, suggesting that EPSC-Exos might represent a strategy to prevent scar formation during wound healing in the clinical setting.

【 授权许可】

CC BY