Induction of hepatic differentiation of mouse bone marrow stromal stem cells by the histone deacetylase inhibitor VPA.

Journal of Cellular and Molecular Medicine
Y ChenGuo-Rong Zhang

Abstract

Bone marrow stromal stem cells (BMSSCs) may have potential to differentiate in vitro and in vivo into hepatocytes. Here, we investigated the effects of valproic acid (VPA) involved in epigenetic modification, a direct inhibitor of histone deacetylase, on hepatic differentiation of mouse BMSSCs. Following the treatment of 2.5 mM VPA for 72 hrs, the in vitro expanded, highly purified and functionally active mouse BMSSCs from bone marrow were either exposed to some well-defined cytokines and growth factors in a sequential way (fibroblast growth factor-4 [FGF-4], followed by HGF, and HGF + OSM + ITS + dexamethasone, resembling the order of secretion during liver embryogenesis) or transplanted (caudal vein) in mice submitted to a protocol of chronic injury (chronic i.p. injection of CCl4). Additional exposure of the cells to VPA considerably improved the in vitro differentiation, as demonstrated by a more homogeneous cell population exhibited epithelial morphology, increasing expression of hepatic special genes and enhanced hepatic functions. Further more, in vivo results indicate that the pre-treatment of VPA significantly increased the homing efficiency of BMSSCs to the site of liver injury and, additionally, for supporting hepati...Continue Reading

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Citations

Aug 28, 2010·Journal of Biomedicine & Biotechnology·Sébastien ChateauvieuxMarc Diederich
Nov 6, 2009·World Journal of Gastroenterology : WJG·Xue-Jun DongJian-Zhong Shao
Jul 9, 2010·World Journal of Gastroenterology : WJG·Xue-Jun DongJian-Zhong Shao
May 6, 2015·The International Journal of Biochemistry & Cell Biology·Arshak R Alexanian
Jun 23, 2019·International Journal of Molecular Sciences·Wachira PantaRangsun Parnpai
Jul 27, 2018·Inflammation·Qiufang DengYongqing Li
Oct 29, 2020·Molecular and Cellular Biochemistry·Saman RashidKanwal Haneef

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