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Enhancing Human Cardiomyocyte Differentiation from Induced Pluripotent Stem Cells with Trichostatin A

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Induced Pluripotent Stem (iPS) Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1357))

Abstract

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 describe a method for enhanced cardiomyocyte production from human iPS cells by treating embryoid bodies with a histone deacetylase inhibitor, trichostatin A (TSA), together with activin A and bone morphogenetic protein (BMP)-4. The resulting cardiomyocytes expressed cardiac-specific transcription factors and contractile proteins at both gene and protein levels. Functionally, the contractile embryoid bodies (EBs) displayed calcium cycling and were responsive to the chronotropic agents isoprenaline (0.1 μM) and carbachol (1 μM). The cardiomyocytes derived from human iPS cells may be used to engineer functional cardiac muscle tissue for studying pathophysiology of cardiac disease, for drug discovery test beds, and potentially for generation of cardiac grafts to surgically replace damaged myocardium.

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Acknowledgment

These studies were supported by grants from the National Heart Foundation and National Health and Medical Research Council of Australia (1024817; 1056589). GJD is a Principal Research Fellow of NHMRC and AP is a Career Development Fellow of NHMRC. Support is also provided by the JR and JO Wicking Trust, Friedreich’s Ataxia Research Association (research grant and 2012 Keith Michael Andrus Cardiac Research Award), Tony and Gwyneth Lennon Foundation, and the Victorian State Government’s Department of Innovation, Industry and Regional Development’s Operational Infrastructure Support Program.

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Authors and Affiliations

  1. Department of Surgery, O’Brien Institute, University of Melbourne, 42 Fitzroy Street, Fitzroy, VIC, 3065, Australia

    Shiang Y. Lim Ph.D., Priyadharshini Sivakumaran, Gregory J. Dusting & Rodney J. Dilley Ph.D.

  2. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia

    Duncan E. Crombie, Gregory J. Dusting & Alice Pébay

  3. Department of Ophthalmology, University of Melbourne, East Melbourne, VIC, Australia

    Duncan E. Crombie, Gregory J. Dusting & Alice Pébay

  4. Ear Science Institute Australia, University of Western Australia, Nedlands, Crawley, WA, Australia

    Rodney J. Dilley Ph.D.

  5. Ear Sciences Centre, School of Surgery, The University of Western Australia (M509), 35 Stirling Highway, Crawley, WA, 6009, Australia

    Rodney J. Dilley Ph.D.

Authors
  1. Shiang Y. Lim Ph.D.
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  2. Priyadharshini Sivakumaran
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  3. Duncan E. Crombie
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  4. Gregory J. Dusting
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  5. Alice Pébay
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  6. Rodney J. Dilley Ph.D.
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Corresponding authors

Correspondence to Shiang Y. Lim Ph.D. or Rodney J. Dilley Ph.D. .

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Editors and Affiliations

  1. Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

    Kursad Turksen

  2. Mount Sinai Hospital Samuel Lunenfeld Research Inst, Toronto, Ontario, Canada

    Andras Nagy

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© 2014 Springer Science+Business Media New York

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Lim, S.Y., Sivakumaran, P., Crombie, D.E., Dusting, G.J., Pébay, A., Dilley, R.J. (2014). Enhancing Human Cardiomyocyte Differentiation from Induced Pluripotent Stem Cells with Trichostatin A. In: Turksen, K., Nagy, A. (eds) Induced Pluripotent Stem (iPS) Cells. Methods in Molecular Biology, vol 1357. Humana Press, New York, NY. https://doi.org/10.1007/7651_2014_160

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  • DOI: https://doi.org/10.1007/7651_2014_160

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3054-8

  • Online ISBN: 978-1-4939-3055-5

  • eBook Packages: Springer Protocols

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