Golforoush Pelin, Schneider Michael D
National Heart and Lung Institute, Imperial College London, London, W12 0NN UK.
NPJ Regen Med. 2020 Mar 6;5:4. doi: 10.1038/s41536-020-0090-7. eCollection 2020.
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、相关且具有预测性的模型系统的可用性。相反，对于心肌而言，尽管非人类研究结果令人鼓舞，但缺乏用于指导靶点验证和化合物开发的人类临床前模型可能导致了临床试验失败这一长期存在的问题。相比之下，多能干细胞模型产生的人类心肌细胞最近已应用于安全药理学、表型筛选、靶点验证和高通量分析，促进了心脏药物的发现。在此，我们综述了人类多能干细胞模型在心脏药物发现中的影响，讨论了其应用范围、读数和所采用的疾病模型，以及进一步推进这一富有成效的研究模式所面临的挑战和前景。
