Published in:
01-07-2014 | Regenerative Medicine and Stem-cell Therapy (S Wu and P Hsieh, Section Editors)
hiPSC Modeling of Inherited Cardiomyopathies
Authors:
Gwanghyun Jung, PhD, Daniel Bernstein, MD
Published in:
Current Treatment Options in Cardiovascular Medicine
|
Issue 7/2014
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Opinion statement
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.