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Ca2+ signaling of human pluripotent stem cells-derived cardiomyocytes as compared to adult mammalian cardiomyocytes.
Cell Calcium ( IF 4 ) Pub Date : 2020-06-13 , DOI: 10.1016/j.ceca.2020.102244
Xiao-Hua Zhang 1 , Martin Morad 1
Affiliation  

Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) have been extensively used for in vitro modeling of human cardiovascular disease, drug screening and pharmacotherapy, but little rigorous studies have been reported on their biophysical or Ca2+ signaling properties. There is also considerable concern as to the level of their maturity and whether they can serve as reliable models for adult human cardiac myocytes. Ultrastructural difference such as lack of t-tubular network, their polygonal shapes, disorganized sarcomeric myofilament, and their rhythmic automaticity, among others, have been cited as evidence for immaturity of hiPSC-CMs. In this review, we will deal with Ca2+ signaling, its regulation, and its stage of maturity as compared to the mammalian adult cardiomyocytes. We shall summarize the data on functional aspects of Ca2+signaling and its parameters that include: L-type calcium channel (Cav1.2), ICa-induced Ca2+release, CICR, and its parameters, cardiac Na/Ca exchanger (NCX1), the ryanodine receptors (RyR2), sarco-reticular Ca2+pump, SERCA2a/PLB, and the contribution of mitochondrial Ca2+ to hiPSC-CMs excitation-contraction (EC)-coupling as compared with adult mammalian cardiomyocytes. The comparative studies suggest that qualitatively hiPSC-CMs have similar Ca2+signaling properties as those of adult cardiomyocytes, but quantitative differences do exist. This review, we hope, will allow the readers to judge for themselves to what extent Ca2+signaling of hiPSC-CMs represents the adult form of this signaling pathway, and whether these cells can be used as good models of human cardiomyocytes.



中文翻译:

与成年哺乳动物心肌细胞相比,人多能干细胞衍生的心肌细胞的 Ca2+ 信号传导。

人类诱导多能干细胞衍生的心肌细胞 (hiPSC-CM) 已广泛用于人类心血管疾病的体外建模、药物筛选和药物治疗,但关于其生物物理或 Ca 2+信号传导特性的严格研究鲜有报道。对于它们的成熟度以及它们是否可以作为成人心肌细胞的可靠模型,也存在相当大的担忧。超微结构差异,例如缺乏 t 管状网络、它们的多边形形状、无组织的肌节肌丝及其节律自动性等,已被引用为 hiPSC-CM 不成熟的证据。在本次审查中,我们将处理 Ca 2+与哺乳动物成年心肌细胞相比,信号传导、其调节和成熟阶段。我们将总结 Ca 2+信号及其参数的功能方面的数据,包括:L 型钙通道 (Cav1.2)、I Ca诱导的 Ca 2+释放、CICR 及其参数、心脏 Na/Ca 交换器(NCX1)、兰尼碱受体 (RyR2)、肌网状 Ca 2+泵、SERCA2a/PLB 以及线粒体 Ca 2+与成年哺乳动物心肌细胞相比对 hiPSC-CMs 激发-收缩 (EC) 耦合的贡献。比较研究表明定性hiPSC-CMs 具有相似的 Ca 2+信号特性与成体心肌细胞的信号特性相同,但确实存在数量上的差异。我们希望这篇综述能让读者自己判断hiPSC-CMs 的Ca 2+信号在多大程度上代表了这种信号通路的成体形式,以及这些细胞是否可以用作人类心肌细胞的良好模型。

更新日期:2020-06-23
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