Chitosan Wound Dressings Incorporating Exosomes Derived from MicroRNA-126-Overexpressing Synovium Mesenchymal Stem Cells Provide Sustained Release of Exosomes and Heal Full-Thickness Skin Defects in a Diabetic Rat Model
Chitosan Wound Dressings Incorporating Exosomes Derived from MicroRNA-126-Overexpressing Synovium Mesenchymal Stem Cells Provide Sustained Release of Exosomes and Heal Full-Thickness Skin Defects in a Diabetic Rat Model
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DOI：
10.5966/sctm.2016-0275
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发表时间：
2017-03-01
影响因子：
6
通讯作者：
Zhang, Chang-Qing
中科院分区：
文献类型：
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作者：
Tao, Shi-Cong;Guo, Shang-Chun;Zhang, Chang-Qing
有必要找到更好的策略来促进伤口愈合，特别是慢性伤口，这仍然是一个挑战。我们发现滑膜间充质干细胞（SMSCs）具有强烈促进成纤维细胞增殖的能力；然而，它们在促进血管生成方面是无效的。我们利用基因过表达技术，过表达microRNA-126-3p (miR-126-3p)，将内皮祖细胞的血管生成能力转移到SMSCs中，促进血管生成。我们测试了一种治疗策略，包括来自mir -126-3p过表达的SMSCs的控释外泌体与壳聚糖的结合。我们的体外结果显示，来自过表达mir -126-3p的SMSCs （SMSC-126-Exos）的外泌体以剂量依赖性的方式刺激了人真皮成纤维细胞和人真皮微血管内皮细胞（HMEC-1）的增殖。此外，SMSC-126-Exos还促进了HMEC-1的迁移和管的形成。在糖尿病大鼠模型中测试该系统，我们发现该方法可以加速再上皮化，激活血管生成，促进体内胶原成熟。这些数据为SMSC-126-Exos治疗皮肤伤口的潜力提供了第一个证据，并表明修饰细胞（例如，通过基因过表达）和使用这些修饰细胞衍生的外显体提供了一种潜在的药物传递系统，并可能为未来的治疗提供无限的可能性。
There is a need to find better strategies to promote wound healing, especially of chronic wounds, which remain a challenge. We found that synovium mesenchymal stem cells (SMSCs) have the ability to strongly promote cell proliferation of fibroblasts; however, they are ineffective at promoting angiogenesis. Using gene overexpression technology, we overexpressed microRNA-126-3p (miR-126-3p) and transferred the angiogenic ability of endothelial progenitor cells to SMSCs, promoting angiogenesis. We tested a therapeutic strategy involving controlled-release exosomes derived from miR-126-3p-overexpressing SMSCs combined with chitosan. Our in vitro results showed that exosomes derived from miR-126-3p-overexpressing SMSCs (SMSC-126-Exos) stimulated the proliferation of human dermal fibroblasts and human dermal microvascular endothelial cells (HMEC-1) in a dose-dependent manner. Furthermore, SMSC-126-Exos also promoted migration and tube formation of HMEC-1. Testing this system in a diabetic rat model, we found that this approach resulted in accelerated reepithelialization, activated angiogenesis, and promotion of collagen maturity in vivo. These data provide the first evidence of the potential of SMSC-126-Exos in treating cutaneous wounds and indicate that modifying the cells-for example, by gene overexpression-and using the exosomes derived from these modified cells provides a potential drug delivery system and could have infinite possibilities for future therapy.