Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis
Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis
复制标题
受过教育的间充质干细胞释放的外泌体通过促进血管生成加速皮肤伤口愈合
DOI：
10.1111/cpr.12830
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发表时间：
2020-07-01
影响因子：
8.5
通讯作者：
Jin, Yan
中科院分区：
文献类型：
--
作者：
Qiu, Xinyu;Liu, Jin;Jin, Yan
目的皮肤是人体与外界环境联系的主要界面，是多种损伤的易感部位。间充质干细胞（MSC）治疗已被广泛应用，并成为一种有前景的治疗策略。化学制剂、缺氧或基因修饰预处理可部分保护间充质干细胞免受损伤，预处理后的间充质干细胞在减轻损伤方面表现出更好的分化、归巢能力、存活和旁分泌作用。本研究的目的是研究从培养的间充质干细胞中提取的外泌体是否有助于加速伤口愈合过程。材料和方法我们从两种培养的间充质干细胞中提取外泌体，并将其用于皮肤伤口愈合模型。研究了外泌体对内皮细胞的促血管生成作用。结果我们首先发现新生儿血清外泌体预处理MSCs后，其生物学功能和治疗效果均有显著改善。此外，我们从培养的MSCs中提取外泌体，并将其用于直接治疗皮肤损伤模型。我们发现，先前经新生儿血清教育的MSCs释放的外泌体在治疗效果上表现更为突出。在机制上，我们发现受体内皮细胞（ECs）是靶向的，外泌体通过调节AKT/eNOS通路促进其功能，促进血管生成。结论：我们的研究结果揭示了从培养的间质干细胞中获得的升级外泌体作为一种有前途的无细胞治疗策略对皮肤伤口愈合的积极作用。
Objectives Skin serves as the major interface between the external environment and body which is liable to many kinds of injuries. Mesenchymal stem cell (MSC) therapy has been widely used and became a promising strategy. Pre-treatment with chemical agents, hypoxia or gene modifications can partially protect MSCs against injury, and the pre-treated MSCs show the improved differentiation, homing capacity, survival and paracrine effects regard to attenuating injury. The aim of this study was to investigate whether the exosomes from the educated MSCs contribute to accelerate wound healing process. Materials and methods We extracted the exosomes from the two educated MSCs and utilized them in the cutaneous wound healing model. The pro-angiogenetic effect of exosomes on endothelial cells was also investigated. Results We firstly found that MSCs pre-treated by exosomes from neonatal serum significantly improved their biological functions and the effect of therapy. Moreover, we extracted the exosomes from the educated MSCs and utilized them to treat the cutaneous wound model directly. We found that the released exosomes from MSCs which educated by neonatal serum before had the more outstanding performance in therapeutic effect. Mechanistically, we revealed that the recipient endothelial cells (ECs) were targeted and the exosomes promoted their functions to enhance angiogenesis via regulating AKT/eNOS pathway. Conclusions Our findings unravelled the positive effect of the upgraded exosomes from the educated MSCs as a promising cell-free therapeutic strategy for cutaneous wound healing.