Extracellular vesicle-based therapeutic strategies for spinal cord injury.

Abstract

Spinal cord injury (SCI) is a highly disabling disorder of the central nervous system for which no curative therapy is currently available. In recent years, extracellular vesicles - particularly exosomes - have been investigated as cell-free therapeutic approaches in experimental models, owing to their low immunogenicity, favorable biocompatibility and capacity to traverse the blood-spinal cord barrier under specific conditions or delivery routes. This Review summarizes the therapeutic activities and mechanisms of exosomes from diverse sources - including mesenchymal stem cells, immune cells and neural cells - in SCI repair. Reported mechanisms include modulation of the inflammatory microenvironment; inhibition of apoptosis and pyroptosis; mitigation of ferroptosis; promotion of angiogenesis and axonal regeneration; and restriction of glial scar formation. We also discuss advances aimed at enhancing exosome efficacy through cell preconditioning, engineering strategies and integration with biomaterials. Although exosome-based approaches are promising, challenges remain in standardization, targeted delivery and long-term safety. Future work should elucidate the underlying mechanisms and advance clinical translation to robustly evaluate the therapeutic potential of exosomes for SCI repair.