利用人多能干细胞衍生心肌细胞研究药物诱导的心脏毒性。

Agnes Maillet, Kim Peng Tan, Liam R Brunham
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引用次数: 3

摘要

药物性心脏毒性是药物退出市场最常见的原因之一。管理药物性心脏毒性风险的一个主要障碍是缺乏研究心脏安全性的相关模型。人多能干细胞源性心肌细胞(hPSC-CMs)显示了人类心肌的许多特征,具有无限的供应,在药物发现和心脏毒性筛选方面具有巨大的潜力。本单元描述了如何使用多能干细胞衍生的心肌细胞来研究药物诱导的心脏毒性,以阿霉素为例。我们提出了一个工作流,解释了使用CRISPR/Cas9系统编辑hPSC和将hPSC分化为心肌细胞的过程。我们还报道了药物对活性氧产生、细胞内钙浓度、DNA双链断裂形成、基因表达和hspc - cms电生理特性的影响。©2017 by John Wiley & Sons, Inc。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Use of Human Pluripotent Stem Cell Derived-Cardiomyocytes to Study Drug-Induced Cardiotoxicity.

Drug-induced cardiotoxicity is the one of the most common causes of drug withdrawal from market. A major barrier in managing the risk of drug-induced cardiotoxicity has been the lack of relevant models to study cardiac safety. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have great potential in drug discovery and cardiotoxcity screens as they display many characteristics of the human myocardium and offer unlimited supply. This unit describes how to use pluripotent stem cells derived cardiomyocytes to study drug-induced cardiotoxicty using doxorubicin as an example. We present a workflow that explains procedure for editing hPSC using the CRISPR/Cas9 system and for differentiation of hPSC into cardiomyocytes. We also report protocols to study drug effect on ROS production, intracellular calcium concentration, formation of DNA double strand breaks, gene expression and electrophysiological properties of hPSC-CMs. © 2017 by John Wiley & Sons, Inc.

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