Sodium Butyrate Pre-Treatment Enhances Hepatic Differentiation of Bone Marrow Mesenchymal Stem Cells Under Liver-Specific Factors Induction In Vitro

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.

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In vitro hepatic differentiation of human bone marrow mesenchymal stem cells under differential exposure to liver-specific factors

Translational Research ◽

10.1016/j.trsl.2009.05.007 ◽

2009 ◽

Vol 154 (3) ◽

pp. 122-132 ◽

Cited By ~ 49

Author(s):

Mihaela Chivu ◽

Simona O. Dima ◽

Cosmin I. Stancu ◽

Camelia Dobrea ◽

Valentina Uscatescu ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Hepatic Differentiation ◽

Marrow Mesenchymal Stem Cells ◽

Specific Factors ◽

Differential Exposure

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Zebularine Promotes Hepatic Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells by Interfering with p38 MAPK Signaling

Stem Cells International ◽

10.1155/2018/9612512 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Yong-Heng Luo ◽

Juan Chen ◽

En-Hua Xiao ◽

Qiu-Yun Li ◽

Yong-Mei Luo

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Hepatic Differentiation ◽

Urea Production ◽

Marrow Mesenchymal Stem Cells ◽

Hepatocyte Growth

Demethylating agent zebularine is reported to be capable of inducing differentiation of stem cells by activation of methylated genes, though its function in hepatocyte differentiation is unclear. p38 signal pathway is involved in differentiation of hepatocytes and regulating of DNA methyltransferases 1 (DNMT1) expression. However, little is known about the impact of zebularine on bone marrow mesenchymal stem cells (BMMSCs) and p38 signaling during hepatic differentiation. The present study investigated the effects of zebularine on hepatic differentiation of rabbit BMMSCs, as well as the role of p38 on DNMT1 and hepatic differentiation, with the aim of developing a novel strategy for improving derivation of hepatocytes. BMMSCs were treated with zebularine at concentrations of 10, 20, 50, and 100 μM in the presence of hepatocyte growth factor; changes in the levels of hepatic-specific alpha-fetoprotein and albumin were detected and determined by RT-PCR, WB, and immunofluorescence staining. Expression of DNMT1 and phosphorylated p38 as well as urea production and ICG metabolism was also analyzed. Zebularine at concentrations of 10, 20, and 50 μM could not affect cell viability after 48 h. Zebularine treatment leads to an inhibition of DNMT activity and increase of hepatic-specific proteins alpha-fetoprotein and albumin in BMMSCs in vitro; zebularine addition also induced expression of urea production of and ICG metabolism. p38 signal was activated in BMMSCs simulated with HGF; inhibition of p38 facilitated the synthesis of DNMT1 and albumin in cells. Zebularine restrained DNMT1 and phosphorylated p38 which were induced by HGF. Therefore, this study demonstrated that treatment with zebularine exhibited terminal hepatic differentiation of BMMSCs in vitro in association with hepatocyte growth factor; p38 pathway at least partially participates in zebularine-induced hepatic differentiation of rabbit BMMSCs.

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