How Advanced Are Exosomes as Cell-Free Therapeutics for Spinal Cord Injury?

Spinal cord injury (SCI) remains a leading cause of disability worldwide, characterized by complex pathophysiological processes involving primary mechanical damage and secondary cascades of inflammation, oxidative stress, and gliosis. Current cell-based therapies face challenges such as low survival rates, tumorigenicity, and immune rejection. Emerging evidence highlights exosomes-nanoscale extracellular vesicles derived from various cell types-as promising cell-free therapeutic agents. These exosomes mediate intercellular communication by transferring bioactive cargo and exhibit advantages such as low immunogenicity, stability, and blood-spinal cord barrier permeability. This review explores the neuroprotective roles of exosomes from diverse cellular sources in SCI repair. Key mechanisms include regulation of macrophage/microglia polarization, suppression of pyroptosis, promotion of vascularization, inhibition of glial scar formation and enhancement of axonal growth. Challenges remain in optimizing exosome yield, standardization, and clinical translation. Future directions emphasize multi-target therapies, biomarker exploration, and hybrid approaches combining exosomes from multiple. A combination of exosomes with biomaterials or stem cells would amplify the therapeutic effects and reduce the dosage of exosomes. This review underscores the potential of exosome-based therapies to revolutionize SCI treatment by addressing its multifaceted pathophysiology while circumventing risks associated with cell transplantation.