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

Stem Cell Research & Therapy

Ronald A Li²  Kenneth R Boheler³  Maggie Zi Chow¹ 

[1] Department of Physiology, The University of Hong Kong, 4th Floor, 21 Sassoon Road, Laboratory Block, Faculty of Medicine Building, Pokfulam, Hong Kong;Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1234, New York, New York 10029-6574, USA;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

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

Others  :  1147561
DOI  :  10.1186/scrt308

【 摘 要 】

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.

【 授权许可】

   
2013 BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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