Exosomes Derived from miR-126-modified MSCs Promote Angiogenesis and Neurogenesis and Attenuate Apoptosis after Spinal Cord Injury in Rats
Exosomes Derived from miR-126-modified MSCs Promote Angiogenesis and Neurogenesis and Attenuate Apoptosis after Spinal Cord Injury in Rats
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DOI：
10.1016/j.neuroscience.2019.10.043
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发表时间：
2020-01-01
期刊：
影响因子：
3.3
通讯作者：
Lin, Fei-Yue
中科院分区：
文献类型：
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作者：
Huang, Jiang-Hu;Xu, Yang;Lin, Fei-Yue
脊髓损伤（SCI）是一种破坏性的神经系统事件，导致不完全或完全丧失自主运动和感觉功能。直到最近，对于脊髓损伤还没有有效的治疗策略。我们之前的研究表明，microRNA (miR)-126促进了脊髓损伤后的血管生成，减轻了炎症；然而，由于miR在体内的递送效率较低，基于miR-126的治疗效果有限。最近，越来越多的证据表明外泌体可以作为一种有价值的治疗载体，将miR递送到中枢神经系统（CNS）。因此，本研究旨在探讨来自间充质干细胞（MSCs）的外泌体是否可用于递送miR-126治疗脊髓损伤。在这项研究中，我们发现MSCs可以将miR-126装载到分泌的外泌体中。在脊髓损伤大鼠模型中，外泌体将miR-126转移到脊髓损伤部位，减少损伤体积，改善脊髓损伤后的功能恢复。此外，装载mir -126的外泌体促进了脊髓损伤后的血管生成。此外，miR-126外泌体促进脊髓损伤后神经发生并减少细胞凋亡。在体外，我们观察到来自mir -126修饰的MSCs的外泌体通过抑制发芽相关EVH1结构域蛋白1 （SPREDI）和磷酸肌醇-3激酶调控亚基2 （PIK3R2）的表达，促进了人脐静脉内皮细胞（HUVECs）的血管生成和迁移。总之，我们的研究表明，转染miR-126的MSCs衍生的外泌体可以促进血管生成和神经发生，抑制细胞凋亡，促进脊髓损伤后的功能恢复。这些发现表明，来自mir -126修饰的MSCs的外泌体可能作为治疗脊髓损伤的一种新的潜在治疗策略。(c) 2019 ibroElsevier Ltd.出版。版权所有。
Spinal cord injury (SCI) is a devastating neurological event that results in incomplete or complete loss of voluntary motor and sensory function. Until recently, there has been no effective curative strategy for SCI. Our previous study showed that microRNA (miR)-126 promoted angiogenesis and attenuated inflammation after SCI; however, the effect of miR-126-based treatment is limited because of the low efficiency of miR delivery in vivo. Recently, accumulating evidence has indicated that exosomes can serve as a valuable therapeutic vehicle for miR delivery to the central nervous system (CNS). Thus, the present study aimed to investigate whether exosomes derived from mesenchymal stem cells (MSCs) can be used to deliver miR-126 to treat SCI. In this study, we found that MSCs can load miR-126 into secreted exosomes. In a rat model of SCI, exosomes transferred miR-126 to the injured site of the spinal cord, reduced the lesion volume and improved functional recovery after SCI. Additionally, miR-126-loaded exosomes promoted angiogenesis post-SCI. Moreover, the administration of miR-126 exosomes promoted neurogenesis and reduced cell apoptosis after SCI. In vitro, we observed that exosomes derived from miR-126-modified MSCs promoted the angiogenesis and migration of human umbilical venous endothelial cells (HUVECs) by inhibiting the expression of Sprouty-related EVH1 domain-containing protein 1 (SPREDI) and phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2). In conclusion, our study demonstrated that exosomes derived from MSCs transfected with miR-126 may promote angiogenesis and neurogenesis, inhibit apoptosis and promote functional recovery after SCI. These findings suggest that exosomes derived from miR-126-modified MSCs may serve as a novel potential therapeutic strategy for treating SCI. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.