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人多能干细胞衍生的心脏细胞在药物和毒性筛选及疾病建模中的应用:微电极阵列分析可以告诉我们什么。

hiPSCs Derived Cardiac Cells for Drug and Toxicity Screening and Disease Modeling: What Micro- Electrode-Array Analyses Can Tell Us.

机构信息

Department Cardiac Surgery, Medical Center, University of Rostock, 18057 Rostock, Germany.

出版信息

Cells. 2019 Oct 28;8(11):1331. doi: 10.3390/cells8111331.

Abstract

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) have been intensively used in drug development and disease modeling. Since iPSC-cardiomyocyte (CM) was first generated, their characterization has become a major focus of research. Multi-/micro-electrode array (MEA) systems provide a non-invasive user-friendly platform for detailed electrophysiological analysis of iPSC cardiomyocytes including drug testing to identify potential targets and the assessment of proarrhythmic risk. Here, we provide a systematical overview about the physiological and technical background of micro-electrode array measurements of iPSC-CM. We introduce the similarities and differences between action- and field potential and the advantages and drawbacks of MEA technology. In addition, we present current studies focusing on proarrhythmic side effects of novel and established compounds combining MEA systems and iPSC-CM. MEA technology will help to open a new gateway for novel therapies in cardiovascular diseases while reducing animal experiments at the same time.

摘要

人诱导多能干细胞(iPSC)衍生的心肌细胞(CM)已被广泛应用于药物开发和疾病建模。自 iPSC 心肌细胞(CM)首次产生以来,其特征描述已成为研究的主要焦点。多/微电极阵列(MEA)系统为 iPSC 心肌细胞的详细电生理分析提供了一个非侵入性的用户友好平台,包括药物测试以确定潜在的靶点和评估致心律失常风险。在这里,我们提供了一个关于 iPSC-CM 的微电极阵列测量的生理和技术背景的系统概述。我们介绍了动作电位和场电位之间的异同,以及 MEA 技术的优缺点。此外,我们还介绍了当前关注新型和已建立化合物的致心律失常副作用的研究,这些研究结合了 MEA 系统和 iPSC-CM。MEA 技术将有助于为心血管疾病的新疗法开辟新的途径,同时减少动物实验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a7/6912416/574ac424ea4b/cells-08-01331-g001.jpg

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