Scar 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. We 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. We 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. We 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.

中文翻译：

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表皮干细胞来源的外来体通过下调伤口愈合过程中的转化生长因子-β1促进皮肤再生

在临床环境中，皮肤伤口愈合过程中最大的挑战是可能由肌成纤维细胞聚集引起的疤痕形成。研究表明，表皮干细胞（EPSC）可改善伤口愈合并减少疤痕形成。我们调查了皮肤缺陷大鼠模型中EPSC衍生的外泌体（EPSC-Exos）对皮肤伤口愈合的治疗作用。我们还检查了EPSC-Exos特异性microRNA在抑制人类皮肤成纤维细胞（HDF）向成肌纤维细胞分化中的作用。我们发现EPSC-Exos可提高大鼠的伤口愈合速度并减少疤痕形成。此外，EPSC-Exos改善了皮肤附件，神经和血管的再生水平，以及胶原蛋白的自然分布。此外，我们发现这些功能可能是通过抑制转化生长因子-β1（TGF-β1）及其下游基因的活性来实现的。结果显示，某些特定的微小RNA，包括miR-16，let-7a，miR-425-5p和miR-142-3p，都富含EPSC-Exos。EPSC-Exos特异的microRNA，尤其是miR-425-5p和miR-142-3p，通过降低皮肤成纤维细胞中TGF-β1的表达，在抑制成肌纤维细胞分化中起着至关重要的作用。我们发现了EPSC-Exos特异性microRNA的新功能，这表明EPSC-Exos可能代表一种在临床环境中防止伤口愈合过程中形成疤痕的策略。特别是miR-425-5p和miR-142-3p，通过降低皮肤成纤维细胞中TGF-β1的表达，在抑制成肌纤维细胞分化中起着至关重要的作用。我们发现了EPSC-Exos特异性microRNA的新功能，这表明EPSC-Exos可能代表一种在临床环境中防止伤口愈合过程中形成疤痕的策略。特别是miR-425-5p和miR-142-3p，通过降低皮肤成纤维细胞中TGF-β1的表达，在抑制成肌纤维细胞分化中起着至关重要的作用。我们发现了EPSC-Exos特异性microRNA的新功能，这表明EPSC-Exos可能代表一种在临床环境中防止伤口愈合过程中形成疤痕的策略。