Sodium Butyrate Pre-Treatment Enhance Differentiation of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) into Hepatocytes and Improve Liver Injury

Abstract

Objective: The treatment of liver failure by stem cell transplantation has attracted growing interest. Herein, we aim to explore the role of sodium butyrate (NaB) in the hepatic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) under liver-specific factors induction in vitro and vivo. Materials & Methods: We isolated BM-MSCs from the mononuclear cell fraction of rabbit bone marrow samples, and identified the cells by Immunophenotypic analysis. We investigated the effects of different concentrations and induction conditions. The histone deacetylase inhibitor NaB induced hepatic differentiation of BM-MSCs under liver-specific factors induction in vitro. Morphological features, liver-specific gene and protein expression, and functional analyses in vitro and vivo were performed to evaluate the hepatic differentiation of BM-MSCs. Results: Our results showed that pre-treated NaB inhibited the expression of liver-specific protein in a dose-dependent manner. The induction efficiency of NaB with 24h pre-treatment was higher than that of NaB continuous intervention. 0.5 mM 24h NaB pre-treated cells can improve liver tissue damage in vivo. And the liver ALB, AAT and the serum TP were significantly increased, while the serum ALT was significantly reduced. Conclusion: Continuous NaB treatment can inhibit BM-MSCs proliferation in a dose-dependent manner at a certain concentration range. 0.5 mM 24h pre-treatment of NaB enhanced differentiation of BM-MSCs into hepatocytes and improves liver injury in vitro and vivo.