Del Álamo Juan C, Lemons Derek, Serrano Ricardo, Savchenko Alex, Cerignoli Fabio, Bodmer Rolf, Mercola Mark
Department of Mechanical and Aerospace Engineering, University of California, San Diego, 9500 Gilman Drive MC 0411, La Jolla, CA 92093-0411, USA.
Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive MC 0412, La Jolla, CA 92093-0412, USA; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, CA 92037, USA.
Biochim Biophys Acta. 2016 Jul;1863(7 Pt B):1717-27. doi: 10.1016/j.bbamcr.2016.03.003. Epub 2016 Mar 4.
Cardiac drug discovery is hampered by the reliance on non-human animal and cellular models with inadequate throughput and physiological fidelity to accurately identify new targets and test novel therapeutic strategies. Similarly, adverse drug effects on the heart are challenging to model, contributing to costly failure of drugs during development and even after market launch. Human induced pluripotent stem cell derived cardiac tissue represents a potentially powerful means to model aspects of heart physiology relevant to disease and adverse drug effects, providing both the human context and throughput needed to improve the efficiency of drug development. Here we review emerging technologies for high throughput measurements of cardiomyocyte physiology, and comment on the promises and challenges of using iPSC-derived cardiomyocytes to model disease and introduce the human context into early stages of drug discovery. This article is part of a Special Issue entitled: Cardiomyocyte biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
心脏药物研发受到依赖非人类动物和细胞模型的阻碍，这些模型通量不足且生理保真度欠佳，难以准确识别新靶点并测试新的治疗策略。同样，药物对心脏的不良影响难以建模，导致药物在研发过程中甚至上市后出现代价高昂的失败。人诱导多能干细胞衍生的心脏组织是一种潜在的强大手段，可用于模拟与疾病和药物不良影响相关的心脏生理方面，提供改善药物研发效率所需的人体背景和通量。在此，我们综述用于高通量测量心肌细胞生理学的新兴技术，并评论使用诱导多能干细胞衍生的心肌细胞来模拟疾病以及将人体背景引入药物发现早期阶段的前景和挑战。本文是名为《心肌细胞生物学：心脏发育与环境信号整合》特刊的一部分，由马库斯·绍布和休斯·阿布里尔编辑。
