Dimethyl Fumarate Preconditioning can Reinforce the Therapeutic Potential of Bone Marrow Mesenchymal Stem Cells through Trophic Factor Profile Enhancement.

Abstract

Numerous studies have confirmed the therapeutic efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in addressing neurologic disorders. To date, several preconditioning strategies have been designed to improve the therapeutic potential of these stem cells. This study was designed to evaluate the preconditioning effect of dimethyl fumarate (DMF) on the expression of main trophic factors in human BM-MSCs. Initially, the identity of stem cells was confirmed through the evaluation of surface markers and their capacity for osteogenic and adipogenic differentiation using flow cytometry and differentiation assay, respectively. Subsequently, stem cells were subjected to different concentrations of DMF for 72 hours and their viability was defined by MTT assay. Following 72-hour preconditioning period with 10 µM DMF, gene expression was assessed by quantitative RT-PCR. Our findings demonstrated that the isolated stem cells expressed cardinal MSC surface markers and exhibited osteogenic and adipogenic differentiation potential. MTT results confirmed that 10 µM DMF was an optimal dose for maintaining cell viability. Preconditioning of stem cells with DMF significantly upregulated the expression of BDNF, NGF, and NT-3. Despite a slight increase in transcript level of GDNF and VEGF after DMF preconditioning, this difference was not statistically significant. Our findings suggest that DMF preconditioning can enhance the expression of major neurotrophic factors in human BM-MSCs. Given the curative potential of both BM-MSCs and DMF in various neurological disease models and preconditioning outcomes, their combined use may synergistically enhance their neuroprotective properties.