Li Sen, Chen Gaopeng, Li Ronald A
R. A. Li: 5/F Hong Kong Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road, Pokfulam, Hong Kong.
J Physiol. 2013 Nov 1;591(21):5279-90. doi: 10.1113/jphysiol.2013.256495. Epub 2013 Sep 9.
Loss of cardiomyocytes (CMs), which lack the innate ability to regenerate, due to ageing or pathophysiological conditions (e.g. myocardial infarction or MI) is generally considered irreversible, and can lead to conditions from cardiac arrhythmias to heart failure. Human (h) pluripotent stem cells (PSCs), including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSCs), can self-renew while maintaining their pluripotency to differentiate into all cell types, including CMs. Therefore, hPSCs provide a potential unlimited ex vivo source of human CMs for disease modelling, drug discovery, cardiotoxicity screening and cell-based heart therapies. As a fundamental property of working CMs, Ca(2+) signalling and its role in excitation-contraction coupling are well described. However, the biology of these processes in hPSC-CMs is just becoming understood. Here we review what is known about the immature Ca(2+)-handling properties of hPSC-CMs, at the levels of global transients and sparks, and the underlying molecular basis in relation to the development of various in vitro approaches to drive their maturation.
由于衰老或病理生理状况（如心肌梗死或MI）导致的心肌细胞（CMs）丧失，通常被认为是不可逆的，因为心肌细胞缺乏再生的固有能力，这种丧失会导致从心律失常到心力衰竭等各种病症。人类（h）多能干细胞（PSCs），包括胚胎干细胞（ESC）和诱导多能干细胞（iPSCs），可以自我更新，同时保持其多能性，从而分化为包括心肌细胞在内的所有细胞类型。因此，hPSCs为疾病建模、药物发现、心脏毒性筛选和基于细胞的心脏治疗提供了潜在的无限的体外人类心肌细胞来源。作为工作心肌细胞的一个基本特性，Ca(2+)信号及其在兴奋-收缩偶联中的作用已得到充分描述。然而，hPSC-CMs中这些过程的生物学特性才刚刚开始被了解。在这里，我们回顾了关于hPSC-CMs在整体瞬变和火花水平上未成熟的Ca(2+)处理特性的已知情况，以及与驱动其成熟的各种体外方法发展相关的潜在分子基础。
