Stem Cell & Regenerative Medicine Consortium, LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong.
Mol Pharm. 2011 Oct 3;8(5):1495-504. doi: 10.1021/mp2002363. Epub 2011 Sep 8.
Heart diseases are a leading cause of mortality worldwide. Terminally differentiated adult cardiomyocytes (CMs) lack the innate ability to regenerate. Their malfunction or significant loss can lead to conditions from cardiac arrhythmias to heart failure. For myocardial repair, cell- and gene-based therapies offer promising alternatives to donor organ transplantation. Human embryonic stem cells (hESCs) can self-renew while maintaining their pluripotency. Direct reprogramming of adult somatic cells to become pluripotent hES-like cells (also known as induced pluripotent stem cells or iPSCs) has been achieved. Both hESCs and iPSCs have been successfully differentiated into genuine human CMs. In this review, we describe our current knowledge of the structure-function properties of hESC/iPSC-CMs, with an emphasis on their electrophysiology and Ca(2+) handling, along with the hurdles faced and potential solutions for translating into clinical and other applications (e.g., disease modeling, cardiotoxicity and drug screening).
心脏病是全球范围内导致死亡的主要原因。终末分化的成年心肌细胞（CMs）缺乏再生的内在能力。它们的功能障碍或大量丧失会导致心律失常到心力衰竭等疾病。对于心肌修复，基于细胞和基因的治疗为供体器官移植提供了有希望的替代方案。人类胚胎干细胞（hESCs）可以自我更新，同时保持其多能性。已经实现了将成年体体细胞直接重编程为多能性 hES 样细胞（也称为诱导多能干细胞或 iPSCs）。hESCs 和 iPSCs 都已成功分化为真正的人类 CMs。在这篇综述中，我们描述了我们目前对 hESC/iPSC-CMs 的结构-功能特性的了解，重点介绍了它们的电生理学和 Ca（2+）处理，以及在转化为临床和其他应用（例如疾病建模、心脏毒性和药物筛选）方面面临的障碍和潜在解决方案。
