hiPSC Modeling of Inherited Cardiomyopathies
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Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a powerful new model system to study the basic mechanisms of inherited cardiomyopathies. hiPSC-CMs have been utilized to model several cardiovascular diseases, achieving the most success in the inherited arrhythmias, including long QT and Timothy syndromes (Moretti et al. N Engl J Med. 363:1397–409, 2010; Yazawa et al. Nature. 471:230–4, 2011) and arrhythmogenic right ventricular dysplasia (ARVD) (Ma et al. Eur Heart J. 34:1122–33, 2013). Recently, studies have applied hiPSC-CMs to the study of both dilated (DCM) (Sun et al. Sci Transl Med. 4:130ra47, 2012) and hypertrophic (HCM) cardiomyopathies (Lan et al. Cell Stem Cell. 12:101–13, 2013; Carvajal-Vergara et al. Nature. 465:808–12, 2010), providing new insights into basic mechanisms of disease. However, hiPSC-CMs do not recapitulate many of the structural and functional aspects of mature human cardiomyocytes, instead mirroring an immature – embryonic or fetal – phenotype. Much work remains in order to better understand these differences, as well as to develop methods to induce hiPSC-CMs into a fully mature phenotype. Despite these limitations, hiPSC-CMs represent the best current in vitro correlate of the human heart and an invaluable tool in the search for mechanisms underlying cardiomyopathy and for screening new pharmacologic therapies.
KeywordsDilated cardiomyopathy Hypertrophic cardiomyopathy Arrhythmia Stem cells Induced pluripotent stem cells Cardiomyocytes Contractility Development
Compliance with Ethics Guidelines
Conflict of Interest
Dr. Gwanghyun Jung received a grant from Spectrum Child Health at Packard Children's Hospital at Stanford.
Dr. Daniel Bernstein received a grant from the National Institutes of Health.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
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