Mesenchymal Stem Cell-Based Therapies for Central Nervous System Demyelination: A Review of Nonhuman Models

Background: Demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis (MS), are characterized by the progressive loss of myelin, leading to neurological deficits. Current therapies demonstrate limited efficacy in promoting remyelination. This review evaluates the therapeutic potential of mesenchymal stem cells (MSCs) and their derivatives for promoting remyelination in nonhuman models of CNS demyelination. Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science for studies published between 2020 and 2024. Inclusion criteria focused on in vivo and in vitro studies utilizing MSCs, MSC-conditioned media (MSC-CM), or extracellular vesicles (EVs) within experimental models of CNS demyelination. Results: Twenty-four studies met the inclusion criteria. The majority of these investigations demonstrated that MSCs enhance oligodendrocyte progenitor cell (OPC) proliferation and differentiation into mature oligodendrocytes (OLs). Key markers evaluated included NG2, PDGFRα, Olig2, and MBP. Furthermore, MSC-CM and EVs exhibited significant neuroprotective and immunomodulatory effects. Conclusion: MSC-based therapies exhibit promising regenerative potential within preclinical models of CNS demyelination. These findings support further translational research and the advancement of clinical trials targeting remyelination strategies.