Trichostatin A Enhances Differentiation of Human Induced Pluripotent Stem Cells to Cardiogenic Cells for Cardiac Tissue Engineering
Shiang Y Lim, Priyadharshini Sivakumaran, Duncan E Crombie, Gregory J Dusting, Alice Pebay, Rodney J Dilley
STEM CELLS TRANSLATIONAL MEDICINE | WILEY | Published : 2013
Human induced pluripotent stem (iPS) cells are a promising source of autologous cardiomyocytes to repair and regenerate myocardium for treatment of heart disease. In this study, we have identified a novel strategy to enhance cardiac differentiation of human iPS cells by treating embryoid bodies (EBs) with a histone deacetylase inhibitor, trichostatin A (TSA), together with activin A and bone morphogenetic protein 4 (BMP4). Over a narrow window of concentrations, TSA (1 ng/ml) directed the differentiation of human iPS cells into a cardiomyocyte lineage. TSA also exerted an additive effect with activin A (100 ng/ml) and BMP4 (20 ng/ml). The resulting cardiomyocytes expressed several cardiac-sp..View full abstract
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Awarded by National Health and Medical Research Council of Australia
These studies were supported by grants from National Heart Foundation and National Health and Medical Research Council of Australia (NHMRC 509271, 1024817). D.E.C. is supported by an NHMRC Gustav Nossal Scholarship, G.J.D. is a Principal Research Fellow of the NHMRC; and A.P. is a Career Development Award Fellow of the NHMRC. Support is also provided by the J.R. and J.O. Wicking Trust, Friedreich's Ataxia Research Alliance (research grant and 2012 Keith Michael Andrus Cardiac Research Award), the Tony and Gwyneth Lennon Foundation, and the Victorian State Government's Department of Innovation, Industry and Regional Development's Operational Infrastructure Support Program. We thank John Slavin, Laita Bokhari, and Zerina Lokmic for advising us in teratoma analysis, confocal imaging, and histology, respectively. We thank James A. Thomson (University of Wisconsin) for providing the iPS(Foreskin) cell lines.