Successful drug discovery is ultimately contingent on the availability of workable, relevant, predictive model systems. Conversely, for cardiac muscle, the lack of human preclinical models to inform target validation and compound development has likely contributed to the perennial problem of clinical trial failures, despite encouraging non-human results. By contrast, human cardiomyocytes produced from pluripotent stem cell models have recently been applied to safety pharmacology, phenotypic screening, target validation and high-throughput assays, facilitating cardiac drug discovery. Here, we review the impact of human pluripotent stem cell models in cardiac drug discovery, discussing the range of applications, readouts, and disease models employed, along with the challenges and prospects to advance this fruitful mode of research further.

成功的药物发现最终取决于可行的、相关的预测模型系统的可用性。相反，对于心肌来说，尽管非人类结果令人鼓舞，但缺乏人类临床前模型来指导靶点验证和化合物开发，可能导致了临床试验失败的长期问题。相比之下，由多能干细胞模型产生的人心肌细胞最近已应用于安全药理学、表型筛选、靶标验证和高通量测定，促进了心脏药物的发现。在这里，我们回顾了人类多能干细胞模型在心脏药物发现中的影响，讨论了应用范围、读数和所采用的疾病模型，以及进一步推进这种富有成效的研究模式的挑战和前景。