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人干细胞衍生心肌细胞的功能特性

Functional Characterization of Human Stem Cell-Derived Cardiomyocytes.

作者信息

Kirsch Glenn E, Obejero-Paz Carlos A, Bruening-Wright Andrew

机构信息

ChanTest Corporation, Cleveland, Ohio USA.

出版信息

Curr Protoc Pharmacol. 2014;64:11.12.1-26. doi: 10.1002/0471141755.ph1112s64.

Abstract

Cardiac toxicity is a leading contributor to late-stage attrition in the drug discovery process and to withdrawal of approved from the market. In vitro assays that enable earlier and more accurate testing for cardiac risk provide early stage predictive indicators that aid in mitigating risk. Human cardiomyocytes, the most relevant subjects for early stage testing, are severely limited in supply. But human stem cell-derived cardiomyocytes (SC-hCM) are readily available from commercial sources and are increasingly used in academic research, drug discovery and safety pharmacology. As a result, SC-hCM electrophysiology has become a valuable tool to assess cardiac risk associated with drugs. This unit describes techniques for recording individual currents carried by sodium, calcium and potassium ions, as well as single cell action potentials, and impedance recordings from contracting syncytia of thousands of interconnected cells.

摘要

心脏毒性是药物研发过程中导致后期研发失败以及已批准药物退市的主要原因。能够对心脏风险进行更早、更准确检测的体外试验可提供有助于降低风险的早期预测指标。人类心肌细胞作为早期检测最相关的研究对象,其来源极为有限。但是,从商业渠道可轻松获取人类干细胞衍生的心肌细胞(SC-hCM),并且它们在学术研究、药物研发和安全药理学中的应用越来越广泛。因此,SC-hCM电生理学已成为评估药物相关心脏风险的重要工具。本单元介绍了记录钠、钙和钾离子携带的单个电流以及单细胞动作电位的技术,以及来自数千个相互连接细胞的收缩合胞体的阻抗记录技术。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac3/4138727/93420f9ae7ba/nihms573215f1.jpg

相似文献

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Functional Characterization of Human Stem Cell-Derived Cardiomyocytes.人干细胞衍生心肌细胞的功能特性
Curr Protoc Pharmacol. 2014;64:11.12.1-26. doi: 10.1002/0471141755.ph1112s64.
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本文引用的文献

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Electrophysiology of single cardiac cells.
Physiol Rev. 1958 Jan;38(1):41-76. doi: 10.1152/physrev.1958.38.1.41.
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Cardiac excitation-contraction coupling.心脏兴奋-收缩偶联
Nature. 2002 Jan 10;415(6868):198-205. doi: 10.1038/415198a.

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