Evaluation of Edaravone effects on the differentiation of human adipose derived stem cells into oligodendrocyte cells in multiple sclerosis disease in rats

Abstract

AIMS: Among all the treatments for Multiple Sclerosis, stem cell transplantation, such as ADSCs, has attracted a great deal of scientific attention. On the other hand, Edaravone, as an antioxidant component, in combination with stem cells, could increase the survival and differentiation potential of stem cells. MAIN METHODS: 42 rats were divided into: Control, Cuprizone (CPZ), Sham, Edaravone (Ed), hADSCs, and Ed/hADSCs groups. Following induction of cuprizone, induced MS model, behavioral tests were designed to evaluate motor function during. Luxal fast blue staining was done to measure the level of demyelination and remyelination. Immunofluorescent staining was used to evaluate the amount of MBP, OLIG2, and MOG proteins. The mRNA levels of human MBP, MOG, and OLIG2 and rat Mbp, Mog, and Olig2 were determined via RT-PCR. KEY FINDINGS: Flow cytometry analysis exhibited that the extracted cells were positive for CD73 (93.8 ± 3) and CD105 (91.6 ± 3), yet negative for CD45 (2.06 ± 0.5). Behavioral tests, unveiled a significant improvement in the Ed (P < 0.001), hADSCs (P < 0.001), and Ed/hADSCs (P < 0.001) groups compared to the others. In the Ed/hADSCs group, the myelin density was significantly higher than that in the Ed treated and hADSCs treated groups (P < 0.01). Edaravone and hADSCs increased the expression of Mbp, Mog, and Olig2 genes in the cuprizone rat models. Moreover, significant differences were seen between the Ed treated and hADSCs treated groups and the Ed/hADSCs group (P < 0.05 for Mbp and Olig2 and P < 0.01 for Mog). SIGNIFICANCE: Edaravone in combination with hADSCs reduced demyelination and increased oligodendrogenesis in the cuprizone rat models.