title: Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow.
abstract: BACKGROUND
  The capability of human mesenchymal stem cells (hMSC) derived of adult bone marrow to undergo in vitro hepatic differentiation was investigated.
  
  
  RESULTS
  Exposure of hMSC to a cocktail of hepatogenic factors [(fibroblast growth factor-4 (FGF-4), hepatocyte growth factor (HGF), insulin-transferrin-sodium-selenite (ITS) and dexamethasone)] failed to induce hepatic differentiation. Sequential exposure to these factors (FGF-4, followed by HGF, followed by HGF+ITS+dexamethasone), however, resembling the order of secretion during liver embryogenesis, induced both glycogen-storage and cytokeratin (CK)18 expression. Additional exposure of the cells to trichostatin A (TSA) considerably improved endodermal differentiation, as evidenced by acquisition of an epithelial morphology, chronological expression of hepatic proteins, including hepatocyte-nuclear factor (HNF)-3beta, alpha-fetoprotein (AFP), CK18, albumin (ALB), HNF1alpha, multidrug resistance-associated protein (MRP)2 and CCAAT-enhancer binding protein (C/EBP)alpha, and functional maturation, i.e. upregulated ALB secretion, urea production and inducible cytochrome P450 (CYP)-dependent activity.
  
  
  CONCLUSIONS
  hMSC are able to undergo mesenchymal-to-epithelial transition. TSA is hereby essential to promote differentiation of hMSC towards functional hepatocyte-like cells.
authors.affiliation: Dept. Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090, Brussels, Belgium. Sarah.Snykers@vub.ac.be
authors.forename: Sarah
authors.initials: S
authors.lastname: Snykers
authors.forename: Tamara
authors.initials: T
authors.lastname: Vanhaecke
authors.forename: Ann
authors.initials: A
authors.lastname: De Becker
authors.forename: Peggy
authors.initials: P
authors.lastname: Papeleu
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vinken
authors.forename: Ivan
authors.initials: I
authors.lastname: Van Riet
authors.forename: Vera
authors.initials: V
authors.lastname: Rogiers
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000166:cytology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D022781:Hepatocytes / Q000166:cytology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D016130:Immunophenotyping; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2
chemical_list: C000715087:ABCC2 protein, human; D006657:Histones; D006877:Hydroxamic Acids; D000089762:Multidrug Resistance-Associated Protein 2; C012589:trichostatin A