MiR499-5P loaded MSC derived exosomes affect oxidative stress and inflammatory response after spinal cord injury by targeting genes.

Spinal cord injury (SCI) is a severe and prevalent disorder of the central nervous system that leads to sensory and motor dysfunction, with approximately 700,000 new cases reported annually. Recently, miRNA-mRNA regulatory networks have garnered significant attention from researchers. Preliminary evidence from animal models and bioinformatic analyses suggests that altered miRNA expression affects critical pathophysiological processes in SCI. Therefore, the miRNA-target gene interaction network holds promise as a potential therapeutic avenue to promote neural recovery post-SCI. In this study, we demonstrated for the first time that MSC-EXO-miR499-5P can protect neurons and promote the recovery of motor function in SCI mice. First, we selected the GSE2599 dataset through bioinformatic analysis and identified differentially expressed genes (DEGs) using the limma package. Subsequently, we focused on the upregulated DEGs enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to oxidative stress, inflammatory responses, and apoptosis. Following the comparative analysis, miR499-5P was selected for further in vitro and in vivo investigations. Subsequent evaluations demonstrated that MSC-EXO-miR499-5P promoted cell growth, alleviated post-injury oxidative stress and inflammation, and contributed to the repair of the spinal cord microenvironment while enhancing functional recovery in SCI mice. In summary, our findings suggest that MSC-EXO containing miR499-5P represents a novel therapeutic approach for the treatment of SCI.