多电极阵列(MEA)分析分析电生理药物对人干细胞源性心肌细胞的影响

Mike Clements
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引用次数: 29

摘要

需要更多相关和可靠的临床前心脏毒性试验来提高药物安全性并降低药物开发成本。人干细胞来源的心肌细胞(hSC-CMs)为临床前药物安全性筛选提供了一个潜在的模型。一种这样的hSC-CM分析已经显示出实现更多预测性药物心脏风险评估的重大潜力,即MEA分析。多电极阵列(MEA)检测是一种基于电生理学的技术,它使用嵌入每孔培养表面的微电极来测量自发加热hSC-CMs产生的细胞外场电位(FP)的波动。对记录的FP波形的扰动可以作为预测影响药物暴露的离子通道身份的无偏方法。在这里,使用hSC-CMs在48孔MEA板上进行高通量MEA分析,描述了化合物对心肌细胞电生理的影响。在MEA板中制备hSC-CM单层的技术以及将MEA分析实验结果置于背景下的方法也被涵盖。©2016 by John Wiley &儿子,Inc。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multielectrode Array (MEA) Assay for Profiling Electrophysiological Drug Effects in Human Stem Cell-Derived Cardiomyocytes

More relevant and reliable preclinical cardiotoxicity tests are required to improve drug safety and reduce the cost of drug development. Human stem cell-derived cardiomyocytes (hSC-CMs) provide a potential model for the development of superior assays for preclinical drug safety screening. One such hSC-CM assay that has shown significant potential for enabling more predictive drug cardiac risk assessment is the MEA assay. The Multi-electrode Array (MEA) assay is an electrophysiology-based technique that uses microelectrodes embedded in the culture surface of each well to measure fluctuations in extracellular field potential (FP) generated from spontaneously beating hSC-CMs. Perturbations to the recorded FP waveform can be used as an unbiased method of predicting the identity of ion channel(s) impacted on drug exposure. Here, a higher throughput MEA assay using hSC-CMs in 48-well MEA plates is described for profiling compound-induced effects on cardiomyocyte electrophysiology. Techniques for preparing hSC-CM monolayers in MEA plates and methods to contextualize MEA assay experimental results are also covered. © 2016 by John Wiley & Sons, Inc.

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