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Highly Accessed Review

Human pluripotent stem cell-derived cardiomyocytes for heart regeneration, drug discovery and disease modeling: from the genetic, epigenetic, and tissue modeling perspectives

Maggie Zi Chow12, Kenneth R Boheler123 and Ronald A Li124*

Author Affiliations

1 Stem Cell and Regenerative Medicine Consortium, Faculty of Medicine, The University of Hong Kong, 5 Sassoon Road, Hong Kong Jockey Club Building for Interdisciplinary Research, Pokfulam, Hong Kong

2 Department of Physiology, The University of Hong Kong, 4th Floor, 21 Sassoon Road, Laboratory Block, Faculty of Medicine Building, Pokfulam, Hong Kong

3 Molecular Cardiology and Stem Cell Unit, Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA

4 Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1234, New York, New York 10029-6574, USA

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Stem Cell Research & Therapy 2013, 4:97  doi:10.1186/scrt308

Published: 14 August 2013

Abstract

Heart diseases remain a major cause of mortality and morbidity worldwide. However, terminally differentiated human adult cardiomyocytes (CMs) possess a very limited innate ability to regenerate. Directed differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into CMs has enabled clinicians and researchers to pursue the novel therapeutic paradigm of cell-based cardiac regeneration. In addition to tissue engineering and transplantation studies, the need for functional CMs has also prompted researchers to explore molecular pathways and develop strategies to improve the quality, purity and quantity of hESC-derived and iPSC-derived CMs. In this review, we describe various approaches in directed CM differentiation and driven maturation, and discuss potential limitations associated with hESCs and iPSCs, with an emphasis on the role of epigenetic regulation and chromatin remodeling, in the context of the potential and challenges of using hESC-CMs and iPSC-CMs for drug discovery and toxicity screening, disease modeling, and clinical applications.

Keywords:
Human embryonic stem cell; Induced pluripotent stem cell; Cardiomyocyte; Epigenetic regulations; Chromatin remodeling; Histone modification; Regenerative medicine; Cardiac differentiation