Mitochondrial-Immune Dysfunction in MS: Therapeutic Potential of EV-Mediated Transfer.

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system. In this disease, mitochondrial dysfunction contributes to neurodegeneration, axonal loss, and progressive disability. Extracellular vesicle (EV)-mediated mitochondrial transfer has emerged as a promising cell-free strategy to restore mitochondrial homeostasis and modulate immune responses within the CNS. Preclinical studies, particularly in experimental autoimmune encephalomyelitis models, demonstrate that EV-based delivery of mitochondrial cargo improves cellular bioenergetics. In parallel, this approach reduces oxidative stress and neuroinflammation while supporting remyelination and neuroprotection. This review summarizes the mechanistic rationale, current preclinical evidence, and future translational perspectives of EV-mediated mitochondrial therapy in MS.