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人源干细胞诱导分化的功能性心肌细胞与高效微电极阵列系统的联合应用:一种用于药物开发的理想的混合模型检测方法。

Combination of functional cardiomyocytes derived from human stem cells and a highly-efficient microelectrode array system: an ideal hybrid model assay for drug development.

机构信息

ReproCELL Inc., KDX Shin-yokohama 381 Bldg, Kohoku-ku Yokoham, Kanagawa, Japan.

出版信息

Curr Stem Cell Res Ther. 2010 Sep;5(3):227-32. doi: 10.2174/157488810791824502.

DOI:10.2174/157488810791824502
PMID:20214558
Abstract

Human pluripotential stem cells including both embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC) possess self-renewing potency and pluripotentency and can differentiate into virtually any somatic cell type. These features are a distinct advantage for the generation of specific types of human tissue cells in vitro for continuous use in drug development. Recently, an assay system for drug-induced QT interval prolongation using hESC/hiPSC-derived cardiomyocytes and microelectrode arrays (MEA) has been developed. Drug-induced QT interval prolongation (DIQTIP) can lead to sudden cardiac death and is a major safety concern for the drug industry. Regulatory authorities such as the US FDA and the European Medicines Agency require in-vitro testing of all drug candidates to identify potential risk of DIQTIP prior to clinical trials. To reduce the risk of DIQTIP, a routine assay system for in vitro electrophysiological properties using cell-based assays is effective and necessary in early phase of drug discovery. This review discusses developments over the last couple of years for a qualified drug testing method and provides some examples of how hESC/hiPSC-derived cardiomyocytes are beginning to find a practical use for drug discovery and development.

摘要

人多能干细胞包括胚胎干细胞(hESC)和诱导多能干细胞(hiPSC),具有自我更新能力和多能性,可以分化为几乎任何体细胞类型。这些特性对于体外生成特定类型的人类组织细胞以持续用于药物开发具有明显优势。最近,开发了一种使用 hESC/hiPSC 衍生的心肌细胞和微电极阵列(MEA)的药物诱导 QT 间期延长(DIQTIP)检测系统。药物诱导的 QT 间期延长(DIQTIP)可导致心脏性猝死,是药物行业的主要安全关注点。美国 FDA 和欧洲药品管理局等监管机构要求对所有候选药物进行体外测试,以在临床试验前确定潜在的 DIQTIP 风险。为降低 DIQTIP 的风险,使用基于细胞的测定法进行体外电生理特性的常规测定系统在药物发现的早期阶段是有效且必要的。本文综述了过去几年中用于合格药物测试方法的发展,并提供了一些示例,说明 hESC/hiPSC 衍生的心肌细胞如何开始在药物发现和开发中找到实际用途。

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