Transplantation of human adipose derived stem cells with co- overexpressed Leukemia inhibitory factor and beta interferon promote recovery in experimental autoimmune encephalomyelitis (EAE)

Multiple Sclerosis (MS) is the most common demyelinating disease with inflammatory demyelination in central nerve system (CNS). Beside the defect in myelin repair process, the balance change in inflammatory and anti- inflammatory cytokines is one of the most significant factors in MS pathogenesis. This study aimed at evaluating the effects of co-overexpressing beta interferon (IFN-β) and Leukemia inhibitory factor (LIF) in human adipose derived stem cells (IFN-β/LIF-hADSCs) on the experimental autoimmune encephalomyelitis (EAE). 12 days after the induction of EAE on female mice C57Bl/6 with MOG35-55 and the emergence of primary clinical signs, the IFN-β/LIF-hADSCs were injected though the mice tail vein of the EAE mice. The mice were sacrificed after 32 days and the spinal cords of the experimental groups were dissected out for the histopathologic and real time RT-PCR studies. Here, we showed that the clinical scores and infiltration of mononuclear cells of treated mice with IFN-β/LIF-hADSCs were decreased significantly. Remyelination and oligodendrogenesis were significantly increased in the test (IFN-β/LIF-hADSCs) group. The findings revealed that the pattern of inflammatory and anti- inflammatory cytokines gene expression in the IFN-β/LIF-hADSCs group was reversed comparing to control group. Overexpression of LIF as a neurotrophic and IFN-β as an anti-inflammatory cytokine in hADSCs increases the immunomodulatory effect of hADSCs and improves remyelination and oligodendrogenesis in EAE model. This, besides hADSCs capacity for proliferation and differentiation might enhance the treatment efficacy and provide a promising candidate for stem cell-based gene therapy of MS therapy in future.