Lieu Deborah K, Turnbull Irene C, Costa Kevin D, Li Ronald A
Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY, United States.
Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, CA, United States.
Drug Discov Today Dis Models. 2012 Winter;9(4):e209-e217. doi: 10.1016/j.ddmod.2012.06.002.
Human cardiomyocytes (CMs) do not proliferate in culture and are difficult to obtain for practical reasons. As such, our understanding of the mechanisms that underlie the physiological and pathophysiological development of the human heart is mostly extrapolated from studies of the mouse and other animal models or heterologus expression of defective gene product(s) in non-human cells. Although these studies provided numerous important insights, much of the exact behavior in human cells remains unexplored given that significant species differences exist. With the derivation of human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSCs) from patients with underlying heart disease, a source of human CMs for disease modeling, cardiotoxicity screening and drug discovery is now available. In this review, we focus our discussion on the use of hESC/ iPSC-derived cardiac cells and tissues for studying various heart rhythm disorders and the associated pro-arrhythmogenic properties in relation to advancements in electrophysiology and tissue engineering.
人类心肌细胞(CMs)在培养中不会增殖,并且由于实际原因难以获取。因此,我们对人类心脏生理和病理生理发育基础机制的理解大多是从对小鼠和其他动物模型的研究,或在非人类细胞中对缺陷基因产物的异源表达推断而来的。尽管这些研究提供了许多重要的见解,但鉴于存在显著的物种差异,人类细胞中许多确切的行为仍未被探索。随着从患有潜在心脏病的患者中获得人类胚胎干细胞(hESC)和诱导多能干细胞(iPSC),现在有了用于疾病建模、心脏毒性筛选和药物发现的人类CMs来源。在这篇综述中,我们将讨论重点放在使用hESC/iPSC衍生的心脏细胞和组织来研究各种心律失常以及与电生理学和组织工程进展相关的促心律失常特性上。