Toxicity testing in the era of induced pluripotent stem cells: A perspective regarding the use of patient-specific induced pluripotent stem cell-derived cardiomyocytes for cardiac safety evaluation
Toxicity testing in the era of induced pluripotent stem cells: A perspective regarding the use of patient-specific induced pluripotent stem cell-derived cardiomyocytes for cardiac safety evaluation
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DOI：
10.1016/j.cotox.2020.04.001
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发表时间：
2020-10-01
影响因子：
4.6
通讯作者：
Pang, Li
中科院分区：
文献类型：
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作者：
Pang, Li
人类诱导多能干细胞衍生的心肌细胞（iPSC-CMs）的发展开辟了一个新时代，以解决改善药物诱导的心脏毒性预测的挑战。人类iPSC-CM可以从具有不同遗传背景和不同疾病状态的个体中产生，这为在群体水平上评估药物诱导的心脏毒性提供了前所未有的机会，最终实现个性化的心脏安全性预测，并允许在分子和细胞水平上对药物诱导的心脏毒性的遗传易感性进行机理分析。本文综述了使用患者特异性iPSC-CM进行心脏安全性评价的成功应用和局限性。还讨论了iPSC-CM的未来发展方向。本综述的目的是促进人类iPSC-CM技术的进一步发展，以解决药物开发中存在的差距，改善患者对治疗药物敏感性的预测，并加强对严重药物不良反应的上市后监测。
The development of human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has opened a new era to address the challenge of improving drug-induced cardiotoxicity prediction. Human iPSC-CMs can be generated from individuals with diverse genetic backgrounds and varying disease status, which provides unprecedented opportunities to assess drug-induced cardiotoxicity at the population level, ultimately, realizing personalized cardiac safety prediction and permitting mechanistic insights into genetic predisposition of drug-induced cardiotoxicity at the molecular and cellular levels. Reviewed herein are successful applications and limitations in using patient-specific iPSC-CMs for cardiac safety evaluation. Future directions for iPSC-CMs are also discussed. The aim of this review is to promote the further development of human iPSC-CM technology to address existing gaps in drug development, improve the prediction of patient susceptibility to therapeutic drugs, and enhance postmarketing surveillance of severe adverse drug reactions.