In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes
In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes
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DOI：
10.1016/j.bbrc.2009.05.073
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发表时间：
2009-08-07
影响因子：
3.1
通讯作者：
Fukuda, Keiichi
中科院分区：
文献类型：
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作者：
Tanaka, Tomofumi;Tohyama, Shugo;Fukuda, Keiichi
致死性室性心律失常尖端扭转型室性心动过速（TdP）是许多心血管和非心血管药物停药或限制使用的最常见原因。缺乏体外模型来检测对人类心脏细胞的促凋亡作用阻碍了新药的开发。我们假设，最近建立的人类诱导多能干细胞（hiPS）细胞可用于体外药物筛选模型。在这项研究中，hiPS细胞被驱动分化为功能性心肌细胞，其表达心脏标志物，包括Nkx2.5，GATA 4和心房钠尿肽。使用多电极测定法分析hiPS衍生的心肌细胞（hiPS-CM）。离子通道抑制剂的应用导致场电位波形的剂量依赖性变化，并且这些变化与在天然心肌细胞中诱导的变化相同。这项研究表明，hiPS-CM代表了心脏电生理学研究和药物筛选的一个有前途的体外模型。(c)2009 Elsevier Inc. All rights reserved.
The lethal ventricular arrhythmia Torsade de pointes (TdP) is the most common reason for the withdrawal or restricted use of many cardiovascular and non-cardiovascular drugs. The lack of an in vitro model to detect pro-arrhythmic effects on human heart cells hinders the development of new drugs. We hypothesized that recently established human induced pluripotent stem (hiPS) cells could be used in an in vitro drug screening model. In this study, hiPS cells were driven to differentiate into functional cardiomyocytes, which expressed cardiac markers including Nkx2.5, GATA4, and atrial natriuretic peptide. The hiPS-derived cardiomyocytes (hiPS-CMs) were analyzed using a multi electrode assay. The application of ion channel inhibitors resulted in dose-dependent changes to the field potential waveform, and these changes were identical to those induced in the native cardiomyocytes. This study shows that hiPS-CMs represent a promising in vitro model for cardiac electrophysiologic studies and drug screening. (c) 2009 Elsevier Inc. All rights reserved.