Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-beta receptor inhibition

文献类型： 外文期刊

第一作者： Zhang, Yan

作者： Zhang, Yan;Li, Xiheng;Tang, Liang;Duan, Mengna;Li, Jiang;Zhang, Yan;Li, Xiheng;Tang, Liang;Pan, Yingjin;Liu, Yanhong;Li, Jiang;Zhang, Guokun;Zhang, Guokun

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关键词： Cord blood stem cell transplantation; Exosomes; MicroRNAs; Myofibroblasts; Regeneration; Transforming growth factor beta; Wound healing

期刊名称：STEM CELL RESEARCH & THERAPY （ 影响因子：6.832； 五年影响因子：7.153 ）

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年卷期： 2021 年 12 卷 1 期

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收录情况： SCI

摘要： Background Scar formation is a common consequence of skin wound healing, and no effective treatment exists. Umbilical cord blood mesenchymal stem cells (UCB-MSCs) can improve wound healing; however, the role of UCB-MSCs remains unclear and whether they can ameliorate scar formation has not been fully elucidated. Methods To determine the function of UCB-MSCs, we examined and compared the therapeutic effects of UCB-MSCs and UCB-MSC-derived exosomes (UCB-MSC-exo) on skin healing in rats. Moreover, UCB-MSC-exo-specific miRNAs were identified and their effects in inhibiting the human dermal fibroblast (HDF) differentiation into myofibroblasts were investigated. Results Both UCB-MSCs and UCB-MSC-exo accelerated wound closure; reduced scar formation; improved the regeneration of skin appendages, nerves, and vessels; and regulated the natural distribution of collagen fibers in wound healing. Additionally, UCB-MSC-exo suppressed the excessive formation of myofibroblasts and collagen I and increased the proliferation and migration of skin cells in vivo and in vitro. Functional analysis showed that UCB-MSC-derived miRNAs were closely related to the transforming growth factor-beta (TGF-beta) signaling pathway, which could induce myofibroblast differentiation. We identified abundant miRNAs that were highly expressed in UCB-MSC-exo. miR-21-5p and miR-125b-5p were predicted to contribute to TGF-beta receptor type II (TGFBR2) and TGF-beta receptor type I (TGFBR1) inhibition, respectively. Using miRNA mimics, we found that miR-21-5p and miR-125b-5p were critical for anti-myofibroblast differentiation in the TGF-beta 1-induced HDF. Conclusion The effect of UCB-MSCs in stimulating regenerative wound healing might be achieved through exosomes, which can be, in part, through miR-21-5p- and miR-125b-5p-mediated TGF-beta receptor inhibition, suggesting that UCB-MSC-exo might represent a novel strategy to prevent scar formation during wound healing.

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