BM-MSCs suppress experimental autoimmune encephalomyelitis by altering miR-۱۹۳, miR-۱۴۶a, miR-۱۵۵, miR-۲۱ and miR-۳۲۶ expression

Background and aim: Multiple Sclerosis (MS) is a demyelinating neurodegenerative disease has immunological, histopathological, and clinical similarities with its animal model, Experimental Autoimmune Encephalomyelitis (EAE). Cell based-therapies signify promising strategies for the treatment of neurological diseases. MSCs effects may be mediated by several ways such as cell-to-cell communication and exosomes. The purpose of this study was to evaluate the therapeutic effect of BM-MSCs administration in the EAE.Materials and method: EAE was induced in C۵۷BL/۶ mice (n=۳۲) by Myelin Oligodendrocyte Glycoprotein (MOG۳۵-۵۵) and then BM-MSCs ۱×۱۰۶ cells administrated. Clinical and weight examinations were performed daily. Inflammation and demyelination by histology of parts of the CNS of mice will be evaluated. Herein, we investigated pro and anti-inflammatory genes expression, as well as miRNAs that are involved in the differentiation and function of Th cells in the control and progression of EAE by Real-time PCR performed.Results: BM.MSCs markedly ameliorated the clinical symptoms, reduced the inflammation and demyelination of the brain in the EAE. Our findings suggest that increased expression of miR-۱۹۳ miR-۱۴۶a and decrease of miR-۱۵۵ and miR-۲۱ miR-۳۲۶ followed by an increase in expression levels of IL-۱۰, TGF-β, and IL-۴ cytokines; however, the amounts of IFN-γ and IL-۲۷ reduced in treatment groups. Likewise associated with suppressing effects on Th۱ and Th۱۷ immune responses, induction of Treg cells, and immunoregulatory responses in treatment groups.Conclusion: These results provide compelling evidence that immune suppression is modulated by MSC-derived exosomes and underscore the value of BM.MSCs and miRNAs by influencing T cell differentiation and reduction of CNS inflammation, demyelination, and local neurodegeneration.

کلیدواژه ها:

MicroRNA ، Neuroinflammation ، Multiple sclerosis ، Experimental autoimmune encephalomyelitis ، T cell differentiation