Preconditioning enhances neurotrophic factor expression in rat bone marrow mesenchymal stem cells for neuroregenerative applications.

Abstract

Stroke is a leading cause of mortality and disability in adults worldwide. Among the various treatment strategies, cell-based therapies have gained considerable attention due to their regenerative potential. Enhancing the efficacy of stem cells is critical to improve therapeutic outcomes. Dimethyl fumarate (DMF) is one of the drugs that has been recognized for its ability to modulate the paracrine effects of stem cells. This study aimed to investigate the effect of different concentrations of DMF on rat bone marrow mesenchymal stem cells (BM-MSCs). The BM-MSCs viability following treatment with various doses of DMF was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and fluorescein diacetate staining at 24 and 72 hours. After identifying the optimal DMF concentration, BM-MSCs were cultured with selected DMF concentration for 72 hours, and their gene expression profiles of key neurotrophic factors were analyzed using quantitative real-time polymerase chain reaction. Our findings revealed that 1 μM DMF was the optimal concentration for enhancing BM-MSC viability. Treatment with this dose significantly upregulated the expression of brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3, highlighting their potential in promoting neuronal support and regeneration. In contrast, the transcript level of glial-derived neurotrophic factor was significantly reduced, suggesting a selective regulatory effect of DMF on neurotrophic pathways. These findings shed light on the therapeutic promise of DMF in modulating neurotrophic factor expression in BM-MSCs, offering novel insights into its application in regenerative medicine for neurodegenerative conditions.