Human Amniotic Fluid Stem Cell-Derived Exosomes as a Novel Cell-Free Therapy for Cutaneous Regeneration

文献类型： 外文期刊

第一作者： Zhang, Yan

作者： Zhang, Yan;Yan, Jiaqing;Li, Xiheng;Tang, Liang;Duan, Mengna;Zhang, Yan;Li, Xiheng;Tang, Liang;Liu, Yanhong;Chen, Zhenyu;Li, Jiang;Zhang, Guokun;Zhang, Guokun

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关键词： human amniotic fluid stem cells; exosomes; miRNA; scarring; transforming growth factor; wound healing

期刊名称：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY （ 影响因子：6.684； 五年影响因子：7.219 ）

ISSN： 2296-634X

年卷期： 2021 年 9 卷

页码：

收录情况： SCI

摘要： Adult wound healing often results in fibrotic scarring that is caused by myofibroblast aggregation. Human amniotic fluid stem cells (hAFSCs) exhibit significantly anti-fibrotic scarring properties during wound healing. However, it is little known whether hAFSCs directly or indirectly (paracrine) contribute to this process. Using the full-thickness skin-wounded rats, we investigated the therapeutic potential of hAFSC-derived exosomes (hAFSC-exo). Our results showed that hAFSC-exo accelerated the wound healing rate and improved the regeneration of hair follicles, nerves, and vessels, as well as increased proliferation of cutaneous cells and the natural distribution of collagen during wound healing. Additionally, hAFSC-exo suppressed the excessive aggregation of myofibroblasts and the extracellular matrix. We identified several miRNAs, including let-7-5p, miR-22-3p, miR-27a-3p, miR-21-5p, and miR-23a-3p, that were presented in hAFSC-exo. The functional analysis demonstrated that these hAFSC-exo-miRNAs contribute to the inhibition of the transforming growth factor-beta (TGF-beta) signaling pathway by targeting the TGF-beta receptor type I (TGF-beta R1) and TGF-beta receptor type II (TGF-beta R2). The reduction of TGF-beta R1 and TGF-beta R2 expression induced by hAFSC-exo was also confirmed in the healing tissue. Finally, using mimics of miRNAs, we found that hAFSC-exo-miRNAs were essential for myofibroblast suppression during the TGF-beta 1-induced human dermal fibroblast-to-myofibroblast transition in vitro. In summary, this study is the first to show that exosomal miRNAs used in hAFSC-based therapy inhibit myofibroblast differentiation. Our study suggests that hAFSC-exo may represent a strategic tool for suppressing fibrotic scarring during wound healing.

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