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Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis
Cell Proliferation ( IF 8.5 ) Pub Date : 2020-07-01 , DOI: 10.1111/cpr.12830
Xinyu Qiu 1 , Jin Liu 1, 2 , Chenxi Zheng 1, 3 , Yuting Su 4 , Lili Bao 3 , Bin Zhu 1, 5 , Siying Liu 6 , Lulu Wang 7 , Xiao Wang 8 , Yirong Wang 8 , Wanmin Zhao 1, 3 , Jun Zhou 1 , Zhihong Deng 1 , Shiyu Liu 1 , Yan Jin 1
Affiliation  

Abstract 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.

中文翻译:

从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

摘要 目的皮肤是人体与外界环境的主要界面,容易受到多种伤害。间充质干细胞 (MSC) 疗法已被广泛使用并成为一种有前景的策略。用化学试剂、缺氧或基因修饰预处理可以部分保护 MSC 免受损伤,预处理后的 MSC 在减轻损伤方面表现出改善的分化、归巢能力、存活和旁分泌作用。本研究的目的是调查来自受过教育的 MSC 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个受过训练的 MSC 中提取外泌体,并将它们用于皮肤伤口愈合模型。还研究了外泌体对内皮细胞的促血管生成作用。结果我们首先发现用新生儿血清外泌体预处理的MSCs显着改善了其生物学功能和治疗效果。此外,我们从受过教育的 MSC 中提取外泌体,并利用它们直接治疗皮肤伤口模型。我们发现之前用新生儿血清培养的MSCs释放的外泌体在治疗效果上表现更突出。从机制上讲,我们发现受体内皮细胞(EC)是靶向的,外泌体通过调节 AKT/eNOS 通路促进其功能以增强血管生成。结论我们的研究结果揭示了来自受过教育的 MSC 的升级外泌体作为皮肤伤口愈合的有前途的无细胞治疗策略的积极作用。
更新日期:2020-07-01
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