Li Cong, An Yu, Sun Yu, Yang Fan, Xu Quanchen, Wang Zhiguo
The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong Province, 266021, People's Republic of China.
Department of Stomatology, the Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong Province, 266021, People's Republic of China.
Stem Cell Rev Rep. 2022 Aug;18(6):2059-2073. doi: 10.1007/s12015-022-10378-0. Epub 2022 Apr 26.
The differentiation, migration, and proliferation of skin fibroblasts are identified as key factors in cutaneous wound healing. Adipose-derived mesenchymal stem cells (ADMSCs) and their exosomes (ADMSC-Exos) have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms on cutaneous wound healing are still not well understood. In this study, we successfully obtained ADMSC-Exos and found ADMSC-Exos significantly promoted the migration and proliferation of fibroblasts in a dose-dependent manner in vitro. The expression levels of COL-I and COL-III in fibroblasts treated with ADMSC-Exos were significantly increased, while the expression level of α-SMA was decreased. In addition, the enhanced protein expression of WNT2b and β-catenin confirmed the activation of the WNT/β-catenin signaling pathway and the WNT/β-catenin inhibitor (XAV939) reversed the promoting effect of ADMSC-Exos on wound healing and the β-catenin expression. Taken together, our study partially elucidates the mechanism of ADMSC-Exos in wound healing, illustrating the potential of ADMSC-Exos as a new therapeutic approach to promote skin wound healing.
皮肤成纤维细胞的分化、迁移和增殖被认为是皮肤伤口愈合的关键因素。脂肪来源的间充质干细胞（ADMSC）及其外泌体（ADMSC-Exos）被视为组织再生的潜在治疗工具；然而，其在皮肤伤口愈合中的潜在机制仍未完全阐明。在本研究中，我们成功获得了ADMSC-Exos，并发现ADMSC-Exos在体外以剂量依赖的方式显著促进了成纤维细胞的迁移和增殖。用ADMSC-Exos处理的成纤维细胞中COL-I和COL-III的表达水平显著增加，而α-SMA的表达水平降低。此外，WNT2b和β-连环蛋白的蛋白表达增强证实了WNT/β-连环蛋白信号通路的激活，并且WNT/β-连环蛋白抑制剂（XAV939）逆转了ADMSC-Exos对伤口愈合和β-连环蛋白表达的促进作用。综上所述，我们的研究部分阐明了ADMSC-Exos在伤口愈合中的机制，说明了ADMSC-Exos作为促进皮肤伤口愈合的新治疗方法的潜力。
