Human neural stem cell-derived small extracellular vesicles enhance functional recovery after ischemic stroke through...

Endogenous neural stem cells (ENSCs) have multi-lineage differentiation capabilities and are believed to be a natural resource for treating ischemic stroke. However, persistent ischemia and hypoxic stimulation induce ENSCs death and their differentiation into glial cells, thereby limiting endogenous neural repair. Previous research has shown that human neural stem cell-derived small extracellular vesicles (hNSC-sEVs) can improve the survival and differentiation of ENSCs into neurons in rats with cerebral ischemia. However, the mechanism by which hNSC-sEVs regulate ENSCs remains unknown. Here, we found that hNSC-sEVs may function through miR-362-3p to reduce the expression of melanoma cell adhesion molecule (MCAM) in ENSCs, resulting in their survival and neuronal differentiation. Mechanism investigation demonstrated that miR-362-3p in hNSC-sEVs may target the 3'-untranslated region (3'-UTR) of MCAM mRNA to block MCAM translation and activate the Wnt/β-catenin signaling pathway to promote the survival and neuronal differentiation of ENSCs. In summary, this study explored the role and underlying mechanism of hNSC-sEVs in regulating endogenous nerve repair. Thisprovides a promising therapeutic strategy for the treatment of ischemic stroke.