title: Modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells.
abstract: The multi-potentiality of mesenchymal stem cells makes them excellent options for future tissue engineering and clinical therapy, including liver injury. In this study, we investigated the effects of valproic acid (VPA), a direct inhibitor of histone deacetylase (HDAC), on the hepatic differentiation of human bone marrow mesenchymal stem cells (BMMSCs). The cells were found to differentiate into a more homogeneous hepatocyte-like population when pretreated with 5 mM VPA for 72 h. The expression of liver-specific markers was significantly upregulated in the VPA-treated group at the mRNA and protein levels. VPA treatment also significantly enhanced the hepatic functions of the differentiated cells, including glycogen storage, cytochrome P450 activity, AFP and ALB synthesis, and urea production. Further analysis showed that treatment with 5 mM of VPA for 72 h greatly improved the histones H3 and H4 acetylation. These results demonstrated that VPA could considerably improve the hepatic differentiation of human BMMSCs, probably because the chromatin-acetylated state changes upon VPA treatment through its HDAC inhibitory effect. Thus, this study provides a direct research model for producing human hepatocytes for clinical purposes.
authors: Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang Province, PR China.
authors: Xuejun
authors: X
authors: Dong
authors: Ruolang
authors: R
authors: Pan
authors: Hui
authors: H
authors: Zhang
authors: Chao
authors: C
authors: Yang
authors: Jianzhong
authors: J
authors: Shao
authors: Lixin
authors: L
authors: Xiang
mesh_terms: D000107:Acetylation; D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D006657:Histones
references: Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16659-64
references: 15537713
references: Cell. 2004 Mar 5;116(5):639-48
references: 15006347
references: J Immunol Methods. 2005 Oct 20;305(1):39-47
references: 16150456
references: Hepatology. 2004 Dec;40(6):1275-84
references: 15562440
references: Int J Artif Organs. 1994 Feb;17(2):95-106
references: 8039947
references: Adv Cancer Res. 2002;86:41-65
references: 12374280
references: J Hepatol. 2006 Jul;45(1):144-59
references: 16730092
references: J Cell Biochem. 2007 Sep 1;102(1):52-63
references: 17340623
references: Science. 1999 Apr 2;284(5411):143-7
references: 10102814
references: J Cell Mol Med. 2009 Aug;13(8B):2582-2592
references: 18705698
references: Arch Med Res. 2003 Nov-Dec;34(6):600-6
references: 14734100
references: Transfus Clin Biol. 2003 Jun;10(3):103-8
references: 12798841
references: J Cell Biochem. 2007 Feb 1;100(2):362-71
references: 16924670
references: Cytotherapy. 2008;10(7):668-75
references: 18985473
references: Toxicol Sci. 2006 Dec;94(2):330-41; discussion 235-9
references: 16840566
references: J Clin Invest. 2002 May;109(10):1291-302
references: 12021244
references: Mol Cancer. 2006 Dec 11;5:71
references: 17156483
references: Cell Cycle. 2006 Feb;5(3):223-6
references: 16397414
references: Exp Hematol. 2005 Apr;33(4):389-94
references: 15781328
references: Cell Prolif. 2009 Dec;42(6):711-20
references: 19689470
references: Connect Tissue Res. 2007;48(3):132-40
references: 17522996
references: J Cell Biochem. 2005 Oct 15;96(3):533-42
references: 16088945
references: J Biol Chem. 2005 May 20;280(20):19682-8
references: 15764815
references: Gastroenterology. 2007 Mar;132(3):1077-87
references: 17383429