Neural Stem Cell-Derived Exosomes Protect Spinal Cord Injury by the Transfer of miR-31-5p

Abstract

Traumatic spinal cord injury (SCI) is a catastrophic damage that causes changes in its motor function permanently. Reactive astrocytes is a pathological feature of spinal cord injury (SCI). Exosomes take part in the transportation of miRNAs and play an a novel platform for intercellular communication in the central nervous system (CNS). However, the effect of miRNAs in Neuronal stem cells (NSCs) derived exosomes in SCI was unknown. in vivo SCI model and in vitro experiments were performed to investigate the effects and mechanisms of exosomes. NSCs-derived exosomes promoted motor function recovery by shifting astrocytes from the A1 to A2 phenotype. microarray analysis of miRNA showed that miR-31-5p was the most enriched in NSCs-derived exosomes. Bioinformatics, RIP, and luciferase activity predicted IL34 was the target downstream gene of miR-31-5p. Western bloting examined IL34/STAT3 signaling pathway involved in modulating atrocities by the exosomal miR-31-5p. Rescue experiments evaluate that exosomal miR-31-5p shifting astrocytes A1 to A2 phenotype by inhibiting IL34/STAT3 signaling cascades, and promoted motor function recovery in mice after SCI.