Human embryonic stem cell-derived cardiomyocytes: drug discovery and safety pharmacology

被引:9
作者
He, Jia-Qiang [1 ]
January, Craig T. [1 ,2 ]
Thomson, James A. [1 ,3 ,4 ,5 ,6 ]
Kamp, Timothy J. [1 ,2 ,6 ]
机构
[1] Cellular Dynam Int Inc, Madison, WI 53711 USA
[2] Univ Wisconsin, Dept Physiol & Med, Madison, WI 53706 USA
[3] Univ Wisconsin, Dept Anat, Madison, WI 53706 USA
[4] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA
[5] Univ Wisconsin, Genome Ctr Wisconsin, Madison, WI 53706 USA
[6] WiCell Res Inst, Madison, WI USA
关键词
action potential; adult stem cell; cardiomyocytes; directed differentiation; drug discovery; electrophysiology; embryoid body; genetic manipulation; hERG; human embryonic stem cell; in vitro cellular assays; QT prolongation;
D O I
10.1517/17460441.2.5.739
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Human embryonic stem cells (hESCs) can provide potentially unlimited quantities of a wide range of human cell types that can be used in drug discovery and development, basic research and regenerative medicine. In this review, the authors describe the differentiation of hESCs into cardiomyocytes and outline the properties of hESC-derived cardiomyocytes (hESC-CMs), including their cardiac-type action potentials and contractile characteristics. In vitro cellular assays using hESC-CMs, which can be genetically engineered to create target-specific reporters as well as human disease models, will have applications at multiple stages of the drug discovery process. Furthermore, cardiac safety pharmacology assays evaluating the risk of proarrhythmic side effects associated with QT prolongation may be enhanced in their predictive value with the use of hESC-CMs.
引用
收藏
页码:739 / 753
页数:15
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