人iPSCs-KCs源性外泌体治疗增生性瘢痕的作用及机制研究

增生性瘢痕的临床治疗方法目前尚存在着多种缺陷, iPS细胞和外泌体则为其提供了新的治疗途径。我们前期研究结果表明小鼠iPSCs-KCs（iPS细胞分化获得的角质形成细胞）源性外泌体能够显著性抑制成纤维细胞迁移、胶原以及alpha-SMA 表达。由此我们提出假设：人iPSCs-KCs源性外泌体能够发挥与小鼠iPSCs-KCs源性外泌体相同的作用，从而用于治疗增生性瘢痕。因此本研究聚焦于探明人iPSCs-KCs源性外泌体对人正常皮肤成纤维细胞和增生性瘢痕成纤维细胞增殖、迁移、胶原以及alpha-SMA 表达的调控作用；探寻其中的关键蛋白或（和）miRNA并阐明与 TGF-β1/Smad及Wnt/β-catenin通路可能的相互信号网络；进一步体内实验探讨人iPSCs-KCs源性外泌体在治疗兔耳增生性瘢痕的作用。旨在通过本研究为iPS细胞和外泌体成为增生性瘢痕的临床治疗新策略提供理论研究基础。

The clinical treatment of hypertrophic scars still has a variety of defects. Induced pluripotent stem cell (iPSC) and exosomes could offer the better way to meet the challenge. Recently, we found that mouse iPSCs-KCs (iPSCs-derived keratinocytes) -derived exosomes can significantly inhibit migration , collagen and alpha-SMA expression of fibroblast. Thus, we hypothesized that human iPSCs-KCs derived exosomes can play the same role as mouse iPSCs-KCs derived exosomes in fibroblasts of human normal skin and hypertrophic scars , and are used to treat hypertrophic scars. Therefore, this study focuse on the role of human iPSCs-KCs derived exosomes in the proliferation, migration, collagen and α-SMA expression of fibroblasts. The key proteins or miRNAs of the human iPSCs-KCs derived exosomes will be explored and elucidated with TGF-β1/ Smad and Wnt / β-catenin pathway. Furthermore, the effect of human iPSCs-KCs exosomes on the hypertrophic scars in rabbit ear will be studied. The aim of this study is to provide a theoretical basis for the new clinical treatment of iPS cells and exosomes on the hypertrophic scars.