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人类诱导多能干细胞高效定向分化为心肌细胞

Highly efficient directed differentiation of human induced pluripotent stem cells into cardiomyocytes.

作者信息

Burridge Paul W, Zambidis Elias T

机构信息

Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

出版信息

Methods Mol Biol. 2013;997:149-61. doi: 10.1007/978-1-62703-348-0_12.

Abstract

Human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes are a novel source of cells for patient-specific cardiotoxicity drug testing, drug discovery, disease modeling, and regenerative medicine. We describe a versatile and cost-effective protocol for in vitro cardiac differentiation that is effective for a wide variety of hiPSC and human embryonic stem cell (hESC) lines. This highly optimized protocol produces contracting human embryoid bodies (hEB) with a near total efficiency of 94.7  ±  2.4% in less than 9 days, and minimizes the variability in cardiac differentiation commonly observed between various hiPSC and hESC lines. The contracting hEB derived using these methods contain high percentages of pure functional cardiomyocytes, highly reproducible electrophysiological profiles, and pharmacologic responsiveness to known cardioactive drugs.

摘要

人诱导多能干细胞(hiPSC)来源的心肌细胞是用于患者特异性心脏毒性药物测试、药物发现、疾病建模和再生医学的新型细胞来源。我们描述了一种通用且经济高效的体外心脏分化方案,该方案对多种hiPSC和人类胚胎干细胞(hESC)系均有效。这种高度优化的方案在不到9天的时间内产生收缩性人类胚状体(hEB),总效率接近94.7±2.4%,并最大限度地减少了不同hiPSC和hESC系之间常见的心脏分化变异性。使用这些方法衍生的收缩性hEB含有高比例的纯功能性心肌细胞、高度可重复的电生理特征以及对已知心脏活性药物的药理反应性。

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