Finding the rhythm of sudden cardiac death: new opportunities using induced pluripotent stem cell-derived cardiomyocytes.
Finding the rhythm of sudden cardiac death: new opportunities using induced pluripotent stem cell-derived cardiomyocytes.
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DOI：
10.1161/circresaha.116.304494
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发表时间：
2015-06-05
影响因子：
20.1
通讯作者：
Wu JC
中科院分区：
文献类型：
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作者：
Sallam K;Li Y;Sager PT;Houser SR;Wu JC
心源性猝死（SCD）是结构性心脏病、基因突变或影响心脏离子通道的获得性疾病患者的常见死亡原因。存在广泛的平台来模拟和研究与SCD相关的疾病。人类临床研究是繁琐的，并且受到可以在人类受试者上进行的调查范围的阻碍。动物模型受限于其与人类心脏电生理的同源程度，包括离子通道表达。最常用的细胞模型是细胞转染模型，它能够模拟单个离子通道的表达，提供对动作电位谱变化的不完全了解。诱导多能干细胞衍生心肌细胞（iPSC-CMs）与成人心肌细胞相似，但不完全相同，为研究导致SCD的心律失常提供了新的平台。各种各样的平台存在表型细胞模型，包括传统和自动化膜片钳，多电极阵列和计算建模。iPSC-CMs已被用于研究长QT综合征、儿茶酚胺能多形性室性心动过速、肥厚性心肌病等遗传性心脏疾病。虽然iPSC-CMs不同于成人心肌细胞，但它们为推进SCD的科学和临床护理提供了一个强大的平台。
Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD.