Exosomes as biomarker-diagnostics and therapeutics for multiple sclerosis: promise, pitfalls, and the rising role of milk-derived exosomes, towards next-generation precision medicine

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the central nervous system (CNS) characterized by inflammation, neurodegeneration, and failed remyelination. Extracellular vesicles (EVs), including exosomes, mediate intercellular communication by shuttling proteins, lipids, and nucleic acids. In MS, EVs participate in antigen presentation, blood–brain barrier (BBB) dysfunction, and neuron–glia crosstalk; their molecular cargo can reflect the cellular state of origin, making them attractive candidates as minimally invasive biomarkers. Parallel advances suggest EVs as promising drug-delivery vehicles capable of targeting the CNS. Mesenchymal stem cell (MSC)-derived exosomes have emerged as particularly promising, suppressing pro-inflammatory microglia, promoting oligodendrocyte maturation, and supporting remyelination in preclinical models. In the broader landscape of neurodegenerative diseases, exosomes exhibit a complex bidirectional regulatory role, serving both as pathological carriers facilitating the transcellular propagation of toxic proteins and as endogenous regulatory systems delivering anti-inflammatory factors and neurotrophic molecules. Among EV sources, milk-derived exosomes (MDEs) are abundant, orally bioavailable, stable in the gastrointestinal tract, and increasingly shown to cross biological barriers and modulate immunity—features that warrant serious consideration for MS diagnostics and therapeutics. Here, we summarize state-of-the-art evidence on the roles of EVs in MS pathobiology, candidate diagnostic signatures, and therapeutic strategies encompassing tolerogenic, anti-inflammatory, and remyelinating approaches. We review MDEs in depth: their composition, isolation rigor, manufacturability from dairy streams, biodistribution, and engineering for CNS targeting. We conclude with a translational roadmap and a critical appraisal of outstanding challenges in standardization, specificity, safety, and regulation, towards next-generation precision medicine in MS.