Human bone marrow‐derived mesenchymal stem cells induce Th2‐polarized immune response and promote endogenous repair in animal models of multiple sclerosis

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Abstract
Cell‐based therapies are attractive approaches to promote myelin repair. Recent studies demonstrated a reduction in disease burden in mice with experimental allergic encephalomyelitis (EAE) treated with mouse mesenchymal stem cells (MSCs). Here, we demonstrated human bone marrow‐derived MSCs (BM‐hMSCs) promote functional recovery in both chronic and relapsing‐remitting models of mouse EAE, traced their migration into the injured CNS and assayed their ability to modulate disease progression and the host immune response. Injected BM‐hMSCs accumulated in the CNS, reduced the extent of damage and increased oligodendrocyte lineage cells in lesion areas. The increase in oligodendrocytes in lesions may reflect BM‐hMSC‐induced changes in neural fate determination, since neurospheres from treated animals gave rise to more oligodendrocytes and less astrocytes than nontreated neurospheres. Host immune responses were also influenced by BM‐hMSCs. Inflammatory T‐cells including interferon gamma producing Th1 cells and IL‐17 producing Th17 inflammatory cells and their associated cytokines were reduced along with concomitant increases in IL‐4 producing Th2 cells and anti‐inflammatory cytokines. Together, these data suggest that the BM‐hMSCs represent a viable option for therapeutic approaches.