High throughput physiological screening of iPSC-derived cardiomyocytes for drug development.
High throughput physiological screening of iPSC-derived cardiomyocytes for drug development.
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IPSC衍生的心肌细胞的高通量生理筛查用于药物开发。
DOI：
10.1016/j.bbamcr.2016.03.003
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Mercola M
中科院分区：
文献类型：
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作者：
Del Álamo JC;Lemons D;Serrano R;Savchenko A;Cerignoli F;Bodmer R;Mercola M
心脏药物发现受到依赖非人类动物和细胞模型的阻碍，这些模型的通量和生理保真度不足，无法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也很难建模，导致药物在开发过程中甚至在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代表了对与疾病和药物不良反应相关的心脏生理学方面进行建模的潜在有力手段，提供了提高药物开发效率所需的人类背景和通量。在这里，我们回顾了心肌细胞生理学高通量测量的新兴技术，并评论了使用iPSC衍生的心肌细胞来模拟疾病的前景和挑战，并将人类背景引入药物发现的早期阶段。
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.