Exosomes Derived from miR-126-modified MSCs Promote Angiogenesis and Neurogenesis and Attenuate Apoptosis after Spinal Cord Injury in Rats. (1st January 2020)

• Record Type: Journal Article
• Authors: Huang, Jiang-Hu; Xu, Yang; Yin, Xiao-Ming; Lin, Fei-Yue
• Is Part Of: Neuroscience. Volume 424(2020)
• Page Start: 133
• Page End: 145
• Publication Date: 2020-01-01
• Subjects: BBB Basso, Beattie, and Bresnahan -- BCA bicinchoninic acid -- EXs exosomes -- FBS fetal bovine serum -- HE Hematoxylin-eosin -- HUVECs human umbilical venous endothelial cells -- LEA Lycopersicon esculentum agglutinin -- miR microRNA -- MSCs mesenchymal stem cells -- OGD oxygen glucose deprivation -- PBS phosphate-buffered saline -- PFA paraformaldehyde -- SCI spinal cord injury -- SPRED1 Sprouty-related EVH1 domain-containing protein 1 -- VCV vessel connectivity value -- VN vessel number -- VVF vessel volume fraction -- WB western blotting; miR-126 exosomes -- angiogenesis -- neurogenesis -- apoptosis -- spinal cord injury; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.10.043
• Languages: English
• ISSNs: 0306-4522

Abstract

Graphical abstract: Highlights: miR-126 exosomes efficiently transferred miR-126 to the injured spinal cord. Exosomes containing miR-126 promoted angiogenesis in the spinal cord after SCI by suppressing SPRED1 and PIK3R2. Exosomes containing miR-126 promote neurogenesis and reduce Apoptosis after SCI. Abstract: 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 (SPRED1) 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.