BMSCs differentiated into neurons, astrocytes and oligodendrocytes alleviated the inflammation and demyelination of EAE mice models

Abstract

Multiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity. Currently, effective therapeutic strategy was poorly found in MS. Experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS. Cumulative research have shown that bone marrow mesenchymal stem Cells (BMSCs) transplantation could treat EAE animal models, but the mechanism was divergent. Here, we systematically evaluated whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes to alleviate the symptoms of EAE mice. We used Immunofluorescence staining to detect MAP-2, GFAP, and MBP to evaluate whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes. The effect of BMSCs transplantation on inflammatory infiltration and demyelination in EAE mice were detected by Hematoxylin-Eosin (H&E) and Luxol Fast Blue (LFB) staining, respectively. Inflammatory factors expression was detected by ELISA and RT-qPCR, respectively. Our results showed that BMSCs could be induced to differentiate into neuron cells, astrocytes and oligodendrocyte in vivo and in vitro, and BMSCs transplanted in EAE mice were easier to differentiate than normal mice. Moreover, transplanted BMSCs reduced neurological function scores and disease incidence of EAE mice. BMSCs transplantation alleviated the inflammation and demyelination of EAE mice. Finally, we found that BMSCs transplantation down-regulated the levels of pro-inflammatory factors TNF-α, IL-1β and IFN-γ, and up-regulated the levels of anti-inflammatory factors IL-10 and TGF-β. In conclusion, this study found that BMSCs could alleviate the inflammatory response and demyelination in EAE mice, which may be achieved by the differentiation of BMSCs into neurons, astrocytes and oligodendrocytes in EAE mice.