Hospital of Stomatology, Jilin University, 1500 Qinghua Rd., Changchun, Jilin, 130021, China.
Jilin Provincial Laboratory of Biomedical Engineering, Jilin University, Changchun, China.
Stem Cell Res Ther. 2021 Aug 3;12(1):434. doi: 10.1186/s13287-021-02517-0.
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.
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.
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-β (TGF-β) 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-β receptor type II (TGFBR2) and TGF-β 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-β1-induced HDF.
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-β receptor inhibition, suggesting that UCB-MSC-exo might represent a novel strategy to prevent scar formation during wound healing.
疤痕形成是皮肤创伤愈合的常见后果，目前尚无有效的治疗方法。脐带血间充质干细胞（UCB-MSCs）可改善伤口愈合；然而，UCB-MSCs 的作用尚不清楚，它们是否能改善疤痕形成也尚未完全阐明。
为了确定 UCB-MSCs 的功能，我们检查和比较了 UCB-MSCs 和 UCB-MSC 衍生的外泌体（UCB-MSC-exo）对大鼠皮肤愈合的治疗效果。此外，还鉴定了 UCB-MSC-exo 中的特异性 miRNA，并研究了它们抑制人真皮成纤维细胞（HDF）分化为肌成纤维细胞的作用。
UCB-MSCs 和 UCB-MSC-exo 均加速伤口闭合；减少疤痕形成；改善皮肤附属物、神经和血管的再生；并调节伤口愈合中胶原纤维的自然分布。此外，UCB-MSC-exo 抑制肌成纤维细胞和胶原 I 的过度形成，并增加皮肤细胞在体内和体外的增殖和迁移。功能分析表明，UCB-MSC 来源的 miRNA 与转化生长因子-β（TGF-β）信号通路密切相关，该通路可诱导肌成纤维细胞分化。我们鉴定了大量在 UCB-MSC-exo 中高度表达的 miRNA。miR-21-5p 和 miR-125b-5p 分别被预测为 TGF-β 受体 II（TGFBR2）和 TGF-β 受体 I（TGFBR1）抑制的贡献者。使用 miRNA 模拟物，我们发现 miR-21-5p 和 miR-125b-5p 对于 TGF-β1 诱导的 HDF 中的抗肌成纤维细胞分化至关重要。
UCB-MSCs 刺激再生性伤口愈合的效果可能是通过外泌体实现的，部分原因是通过 miR-21-5p 和 miR-125b-5p 介导的 TGF-β 受体抑制，这表明 UCB-MSC-exo 可能代表一种预防伤口愈合过程中疤痕形成的新策略。
