a Division of Cardiology, Department of Medicine , University of Ottawa Heart Institute , Ottawa , Canada.
b Department of Cellular and Molecular Medicine , University of Ottawa , Ottawa , Canada.
Expert Opin Biol Ther. 2019 Apr;19(4):313-333. doi: 10.1080/14712598.2019.1575359. Epub 2019 Feb 7.
Inherited arrhythmias are an uncommon, but malignant family of cardiac diseases that result from genetic abnormalities in the ion channels and/or structural proteins within cardiomyocytes. Given the inherent differences between species and the limited reproducibility of in vitro heterologous cell models, progress in understanding the mechanisms underlying these malignant diseases has always languished far behind the clinical science and need. The ability to study human induced pluripotent stem cells (iPSCs) derived cardiomyocytes promises to change this paradigm as patient cells have the potential to become testing platforms for disease phenotyping or therapeutic discovery.
This review will outline methods developed to genetically reprogram adult cells into iPSCs, differentiate iPSCs into ex vivo models of adult cardiac tissue and iPSCs-based progress in exploring the mechanisms underlying pro-arrhythmic disease phenotypes.
Despite being discovered less than 15 years ago, several studies have successfully leveraged iPSCs-derived cardiomyocytes to study malignant arrhythmogenic diseases. These models promise to increase our understanding of the pathophysiology underlying these complex diseases and may identify personalized approaches to treatment.
遗传性心律失常是一组罕见但恶性的心脏疾病，源于心肌细胞离子通道和/或结构蛋白的遗传异常。鉴于物种之间的固有差异和体外异源细胞模型的有限可重复性，对这些恶性疾病潜在机制的理解进展一直远远落后于临床科学和需求。研究人类诱导多能干细胞（iPSCs）衍生的心肌细胞的能力有望改变这种模式，因为患者细胞有可能成为疾病表型或治疗发现的测试平台。
本文综述了将成体细胞重编程为 iPSCs 的方法，以及将 iPSCs 分化为成人心脏组织的体外模型，以及基于 iPSCs 的探索致心律失常疾病表型潜在机制的进展。
尽管 iPSCs 发现不到 15 年，但已有多项研究成功地利用 iPSCs 衍生的心肌细胞来研究恶性心律失常疾病。这些模型有望提高我们对这些复杂疾病病理生理学的理解，并可能确定针对个体化治疗的方法。
