Synergistic Effects of Hydrogen Peroxide Preconditioning and Valproic Acid on Hepatic Differentiation of Mesenchymal Stem Cells.

INTRODUCTION

Ex vivo preconditioning increases the therapeutic potential of mesenchymal stem cells (MSCs) in terms of antioxidant activity, growth factor production, homing, differentiation, and immunomodulation. Therefore, it is considered an effective strategy to be used before transplantation and therapeutic application of MSCs. Histone deacetylase inhibitor (HDACi), valproic acid (VPA), has been reported to induce hepatic differentiation in MSCs. Although individual studies have shown that preconditioning and epigenetic modification enhance the survival and differentiation of MSCs, the combined effects of these therapies have not been fully explored. This study aims to investigate the combined effect of hydrogen peroxide (HO) preconditioning and HDACi (valproic acid) on the differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into hepatic-like cells.

METHODS

MSCs were first preconditioned with HO and then cultured with VPA. The migration and proliferation potential of the treated cells were evaluated using wound healing and colonyforming unit assays. Furthermore, the expression of hepatic genes ( and proteins (AFP, ALB, TAT) was evaluated in all treated groups.

RESULTS

The combined therapy group exhibited enhanced cell migration and proliferation, as evidenced by wound healing and colony-forming unit assays. Additionally, the combined treatment group showed higher expression of , and hepatic genes and TAT protein, suggesting an improved differentiation of stem cells into hepatocytes.

CONCLUSION

In conclusion, the combination of HO and VPA emerges as an important factor in promoting hepatocyte differentiation. However, further studies are required to optimize this protocol for future therapeutics.