High throughput physiological screening of iPSC-derived cardiomyocytes for drug development

被引:89
|
作者
del Alamo, Juan C. [1 ]
Lemons, Derek [2 ,3 ]
Serrano, Ricardo [1 ]
Savchenko, Alex [2 ,3 ,5 ]
Cerignoli, Fabio [4 ]
Bodmer, Rolf [3 ]
Mercola, Mark [2 ,3 ,5 ]
机构
[1] Univ Calif San Diego, Dept Mech & Aerosp Engn, 9500 Gilman Dr MC 0411, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Bioengn, 9500 Gilman Dr MC 0412, La Jolla, CA 92093 USA
[3] Sanford Burnham Prebys Med Discovery Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA
[4] ACEA Biosci Inc, 6779 Mesa Ridge Rd, San Diego, CA 92121 USA
[5] Stanford Cardiovasc Inst, 265 Campus Dr, Stanford, CA 94305 USA
来源
基金
美国国家科学基金会;
关键词
Drug discovery; High content screening; Cardiomyocyte; Heart; Physiology; Automated microscopy; Particle image velocimetry; PLURIPOTENT STEM-CELLS; ACTION-POTENTIALS; BETA(2)-ADRENERGIC RECEPTORS; ELECTRICAL-ACTIVITY; HEART MESODERM; T-TUBULES; IN-VIVO; VOLTAGE; CALCIUM; CONTRACTILITY;
D O I
10.1016/j.bbamcr.2016.03.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (c) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:1717 / 1727
页数:11
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