Generation and characterization of functional cardiomyocytes using induced pluripotent stem cells derived from human fibroblasts

被引:107
作者
Gai, Hui [1 ]
Leung, Elaine Lai-Han [1 ]
Costantino, Peter D. [2 ]
Aguila, Jerell R. [1 ]
Nguyen, David M. [1 ]
Fink, Louis M. [1 ]
Ward, David C. [1 ]
Ma, Yupo [1 ]
机构
[1] Nevada Canc Inst, Div Lab Med, Las Vegas, NV 89135 USA
[2] Columbia Univ Coll Phys & Surg, Cranial Base Surg, Dept Otolaryngol Head & Neck Surg, New York, NY 10019 USA
基金
美国国家卫生研究院;
关键词
Induced pluripotent stem cells; Embryonic stem cells; Somatic cell reprogramming; Cardiomyocytes; Differentiation; CARDIAC DIFFERENTIATION; LINES; MYOCYTES; INDUCTION;
D O I
10.1016/j.cellbi.2009.08.008
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have successfully developed both spontaneous and inductive cardiomyocyte differentiation of iPS cells reprogrammed from human foreskin fibroblasts. The reprogrammed iPS cells morphologically resemble human cardiomyocytes which can beat. RT-PCR and immunostaining show that cardiac markers are expressed that are comparable to the differentiation pattern of authentic human embryonic stem cells, indicating the existence of both immature and mature differentiated cardiomyocytes. 5-Azacytidine greatly enhanced the efficiency of cardiomyocyte differentiation, whereas dimethylsulfoxide had no effect. Low serum and bone morphogenetic protein-2 marginally improved differentiation efficiency. iPS cell-derived cardiomyocytes changed their beat frequency in response to cardiac drugs, which included ion channel blockers and alpha/beta adrenergic stimulators. Derived cardiomyocytes look promising as an in vitro system for potential drug screen and/or toxicity, making this system closer to practical use in the near future. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1184 / 1193
页数:10
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