Dimethyl fumarate prevents cytotoxicity and apoptosis mediated by oxidative stress in human adipose-derived mesenchymal stem cells.

Abstract

The poor survival rate and undesirable homing of transplanted stem cells are the major challenges in stem cell therapy. Addressing the challenge would improve the therapeutic efficacy of these cells. Dimethyl fumarate (DMF) is an anti-inflammatory drug that exerts its effects through the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Therefore, its cytoprotective effects on human adipose-derived MSCs (hASCs) against various oxidative stresses have been investigated in this study. hASCs were cultured with different concentrations of DMF to evaluate the cytotoxicity of DMF on hASCs using Cell Counting Kit-8 (CCK-8). Besides, the migration ability of the cells after DMF treatment was evaluated using the Transwell method. Furthermore, the expression of HO-1 and NQO-1 was determined using RT-PCR. The cytoprotective effects of DMF on hASCs against the oxidative stress caused by H2O2 and Ultra Violet (UV) were evaluated by assessing cell proliferation and apoptosis. Our results demonstrated that under oxidative stress conditions induced by H2O2 and UV, DMF increased the survival rate and proliferation of the cells and prevented apoptosis. Moreover, the expression of HO-1 and NQO-1 was upregulated in hASCs pretreated with DMF which confirms the activation of the Nrf2 pathway. However, DMF significantly decreased migration in hADSCs (P < 0.0001). Our findings indicate that DMF enhances the proliferation capability and viability of hASCs and prevents their apoptosis in harsh stressful microenvironments. However, the applicability of DMF as a cytoprotective factor for the augmentation of hASCs requires in-depth preclinical and clinical studies.