title: Trichostatin A stabilizes the expression of pluripotent genes in human mesenchymal stem cells during ex vivo expansion.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) have been considered as ideal cells for the treatment of a variety of diseases. However, aging and spontaneous differentiation of MSCs during culture expansion dampen their effectiveness. Previous studies suggest that ex vivo aging of MSCs is largely caused by epigenetic changes particularly a decline of histone H3 acetylation levels in promoter regions of pluripotent genes due to inappropriate growth environment.
  
  
  RESULTS
  In this study, we examined whether histone deacetylase inhibitor trichostatin A (TSA) could suppress the histone H3 deacetylation thus maintaining the primitive property of MSCs. We found that in regular adherent culture, human MSCs became flatter and larger upon successive passaging, while the expression of pluripotent genes such as Oct4, Sox2, Nanog, Rex-1, CD133 and TERT decreased markedly. Administration of low concentrations of TSA in culture significantly suppressed the morphological changes in MSCs otherwise occurred during culture expansion, increased their proliferation while retaining their cell contact growth inhibition property and multipotent differentiation ability. Moreover, TSA stabilized the expression of the above pluripotent genes and histone H3 acetylation levels in K9 and K14 in promoter regions of Oct4, Sox2 and TERT.
  
  
  CONCLUSIONS
  Our results suggest that TSA may serve as an effective culture additive to maintain the primitive feature of MSCs during culture expansion.
authors: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Shandong, China.
authors: Bing
authors: B
authors: Han
authors: Jing
authors: J
authors: Li
authors: Zhilong
authors: Z
authors: Li
authors: Ling
authors: L
authors: Guo
authors: Shan
authors: S
authors: Wang
authors: Peishu
authors: P
authors: Liu
authors: Yaojiong
authors: Y
authors: Wu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A