Exosomes as mediators of repair and immunoregulation in multiple sclerosis: a new frontier in cell-free therapy

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system marked by demyelination, inflammation, and progressive neuronal damage. Current immunotherapies reduce relapse frequency but fail to stop silent progression driven by microglial activation or to promote effective remyelination. Mesenchymal stem cells (MSCs) have shown therapeutic promise; however, their clinical use is restricted by issues of survival, distribution, and large-scale production. Increasing evidence indicates that MSC benefits are primarily mediated by their secretome, especially exosomes, nanosized vesicles that carry proteins, lipids, and nucleic acids that modulate immune activity and enhance neuroregeneration. In preclinical models, MSC-derived exosomes suppress pro-inflammatory microglia, increase anti-inflammatory signaling, and stimulate oligodendrocyte maturation and myelin repair. These vesicles can cross the blood-brain barrier, exhibit low immunogenicity, and function as cell-free therapeutics. Early clinical findings in non-neurological disorders confirm their safety, while intranasal administration offers a practical delivery route. Collectively, these insights highlight exosomes as a promising next-generation therapy capable of addressing both inflammation and neurodegeneration in multiple sclerosis.