Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080, China.
Pflugers Arch. 2021 Jul;473(7):1087-1097. doi: 10.1007/s00424-021-02542-1. Epub 2021 Mar 8.
Heart diseases are prevalent worldwide and account for the highest mortality than any other illness. Although investment in drug discovery and development has increased, the amount of drug approvals has seen a progressive decline. Moreover, adverse side effects to the heart have become the most common reasons for preclinical project cessation, partly due to the lack of suitable humanized preclinical models. Human pluripotent stem cells (hPSCs) have emerged as a powerful non-animal platform to model heart disease, to screen for novel drugs, and to test drug cardiotoxicity in a high-throughput and cost-effective manner. Here, we review and discuss recent breakthroughs in the development of cardiovascular modeling and their current and future applications of hPSC-based drug discovery and testing.
心脏病在全球范围内普遍存在,其死亡率高于其他任何疾病。尽管在药物发现和开发方面的投资有所增加,但药物批准的数量却呈逐步下降趋势。此外,心脏的不良反应已成为临床前项目停止的最常见原因,部分原因是缺乏合适的人源化临床前模型。人类多能干细胞(hPSC)已成为一种强大的非动物平台,可用于模拟心脏病、筛选新型药物,并以高通量且具有成本效益的方式测试药物的心脏毒性。在这里,我们回顾和讨论了心血管建模方面的最新突破,以及基于 hPSC 的药物发现和测试的当前和未来应用。