In recent decades, drug development costs have increased by approximately a hundredfold, and yet about 1 in 7 licensed drugs are withdrawn from the market, often due to cardiotoxicity. This review considers whether technologies using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could complement existing assays to improve discovery and safety while reducing socioeconomic costs and assisting with regulatory guidelines on cardiac safety assessments. We draw on lessons from our own work to suggest a panel of 12 drugs that will be useful in testing the suitability of hiPSC-CM platforms to evaluate contractility. We review issues, including maturity versus complexity, consistency, quality, and cost, while considering a potential need to incorporate auxiliary approaches to compensate for limitations in hiPSC-CM technology. We give examples on how coupling hiPSC-CM technologies with Cas9/CRISPR genome engineering is starting to be used to personalize diagnosis, stratify risk, provide mechanistic insights, and identify new pathogenic variants for cardiovascular disease.

中文翻译：

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用人类诱导的多能干细胞衍生心肌细胞解锁个性化生物医学和药物发现：适合目的还是永远难以捉摸？

近几十年来，药物开发成本增加了大约 100 倍，但大约七分之一的许可药物被撤出市场，这通常是由于心脏毒性。本综述考虑了使用人类诱导多能干细胞衍生心肌细胞 (hiPSC-CM) 的技术是否可以补充现有的检测方法，以提高发现和安全性，同时降低社会经济成本并协助制定心脏安全评估的监管指南。我们从我们自己的工作中汲取经验教训，提出一个由 12 种药物组成的小组，这些药物将有助于测试 hiPSC-CM 平台评估收缩性的适用性。我们审查了一些问题，包括成熟度与复杂性、一致性、质量和成本，同时考虑了合并辅助方法以弥补 hiPSC-CM 技术局限性的潜在需求。