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人诱导多能干细胞衍生心肌细胞的兴奋-收缩偶联

Excitation-contraction coupling of human induced pluripotent stem cell-derived cardiomyocytes.

作者信息

Kane Christopher, Couch Liam, Terracciano Cesare M N

机构信息

Laboratory of Cell Electrophysiology, National Heart and Lung Institute, Imperial College London London, UK.

出版信息

Front Cell Dev Biol. 2015 Sep 29;3:59. doi: 10.3389/fcell.2015.00059. eCollection 2015.

Abstract

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold enormous potential in many fields of cardiovascular research. Overcoming many of the limitations of their embryonic counterparts, the application of iPSC-CMs ranges from facilitating investigation of familial cardiac disease and pharmacological toxicity screening to personalized medicine and autologous cardiac cell therapies. The main factor preventing the full realization of this potential is the limited maturity of iPSC-CMs, which display a number of substantial differences in comparison to adult cardiomyocytes. Excitation-contraction (EC) coupling, a fundamental property of cardiomyocytes, is often described in iPSC-CMs as being more analogous to neonatal than adult cardiomyocytes. With Ca(2+) handling linked, directly or indirectly, to almost all other properties of cardiomyocytes, a solid understanding of this process will be crucial to fully realizing the potential of this technology. Here, we discuss the implications of differences in EC coupling when considering the potential applications of human iPSC-CMs in a number of areas as well as detailing the current understanding of this fundamental process in these cells.

摘要

诱导多能干细胞衍生的心肌细胞(iPSC-CMs)在心血管研究的许多领域具有巨大潜力。iPSC-CMs克服了胚胎心肌细胞的许多局限性,其应用范围从促进家族性心脏病的研究、药物毒性筛选到个性化医疗和自体心脏细胞治疗。阻碍充分实现这一潜力的主要因素是iPSC-CMs的成熟度有限,与成年心肌细胞相比,它们表现出许多显著差异。兴奋-收缩(EC)偶联是心肌细胞的一个基本特性,在iPSC-CMs中通常被描述为更类似于新生儿而非成年心肌细胞。由于Ca(2+)处理直接或间接与心肌细胞的几乎所有其他特性相关联,对这一过程的深入理解对于充分实现这项技术的潜力至关重要。在这里,我们讨论在考虑人类iPSC-CMs在多个领域的潜在应用时EC偶联差异的影响,并详细阐述目前对这些细胞中这一基本过程的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2173/4586503/16be7196e664/fcell-03-00059-g0001.jpg

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