Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Sci Rep. 2016 Sep 12;6:32993. doi: 10.1038/srep32993.
Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair.
组织创伤的修复过程漫长且易形成瘢痕,这是目前临床上亟待解决的难题。脂肪间充质干细胞(adipose mesenchymal stem cells,ASCs)在组织再生中发挥重要作用,最近的研究表明,干细胞分泌的外泌体可能通过旁分泌信号发挥作用。本研究探讨了 ASC 来源的外泌体(ASC-Exos)在皮肤创伤愈合中的作用。我们发现 ASC-Exos 可以被成纤维细胞摄取并内化,以剂量依赖性方式刺激细胞迁移、增殖和胶原合成,增加 N-钙黏蛋白、细胞周期蛋白 1、PCNA 和胶原 I、III 的基因表达。体内示踪实验表明,在小鼠皮肤切口模型中,ASC-Exos 可以募集到软组织创伤区域,并显著加速皮肤创伤愈合。组织学分析表明,外泌体全身给药可在创伤愈合的早期增加胶原 I 和 III 的产生,而在晚期,外泌体可能抑制胶原表达,减少瘢痕形成。综上,我们的研究结果表明,ASC-Exos 通过优化成纤维细胞的特性促进皮肤创伤愈合。本研究结果为 ASC-Exos 在软组织修复中的应用提供了新的视角和治疗策略。