Mesenchymal stem cells (MSC) represent a promising therapeutic approach for neurological autoimmune diseases; previous studies have shown that treatment with bone marrow-derived MSC induces immune modulation and reduces disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we show that intravenous administration of adipose-derived MSC (ASC) before disease onset significantly reduces the severity of EAE by immune modulation and decreases spinal cord inflammation and demyelination. ASC preferentially home into lymphoid organs, but migrates also inside the CNS. Most importantly, administration of ASC in chronic established EAE significantly ameliorates the disease course and reduces both demyelination and axonal loss, and induce a Th2-type cytokine shift in T cells. Interestingly, a relevant subset of ASC expresses activated alpha4 integrins and adheres to inflamed brain venules in intravital microscopy experiments. Bioluminescence imaging shows that alpha4 integrins control ASC accumulation in inflamed CNS. Importantly, we found that ASC cultures produce basic fibroblast growth factor, brain-derived growth factor and platelet-derived growth factor-AB. Moreover, ASC infiltration within demyelinated areas is accompanied by increased number of endogenous oligodendrocyte progenitors. In conclusion, we show that ASC have clear therapeutic potential by a bimodal mechanism, by suppressing the autoimmune response in early phases of disease as well as by inducing local neuro-regeneration by endogenous progenitors in animals with established disease. Overall our data suggest that ASC represent a valuable tool for stem cell-based therapy in chronic inflammatory diseases of the CNS.
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