Stem Cell-Derived Exosomes Therapy for Spinal Cord Injury: Mechanisms and Prospects

Abstract:

Spinal cord injury (SCI) is a severe neurological condition often leading to enduring motor, sensory, and autonomic dysfunction. Its pathophysiology involves primary mechanical damage followed by secondary injury processes including axonal disruption, demyelination, excitotoxicity, neuroinflammation, vascular dysfunction, and cell death. Effective treatments that restore neurological function remain scarce. Exosomes (Exos) are nanoscale extracellular vesicles that mediate intercellular communication. Evidence indicates that Exos derived from mesenchymal stem cells (MSCs), neural stem cells (NSCs), and other progenitor populations produce therapeutic effects in SCI models. These effects are mediated through modulation of neuroinflammation, inhibition of apoptosis, preservation of vascular integrity, facilitation of local axonal sprouting and adaptive plasticity within spared neural tissue, and promotion of remyelination. Compared with cell-based therapies, Exos offer lower immunogenicity, reduced tumorigenic potential, and improved stability. Nevertheless, clinical translation faces obstacles including Exos heterogeneity, low yield, limited targeting specificity, and lack of standardized isolation and storage protocols. Emerging approaches such as Exos engineering, artificial Exos, and gene delivery systems are under investigation. This review summarizes SCI pathology and evaluates the therapeutic potential, limitations, and future directions of Exos-based interventions. Importantly, existing data suggest that Exos predominantly influence the post-injury microenvironment and enhance adaptive plasticity rather than promoting true long-distance axonal regeneration. This distinction requires rigorous validation in future studies.