title: Multielectrode Array (MEA) Assay for Profiling Electrophysiological Drug Effects in Human Stem Cell-Derived Cardiomyocytes.
abstract: 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.
authors.affiliation: GE Healthcare Life Sciences, Maynard Centre, Forest Farm, Whitchurch, Cardiff, United Kingdom.
authors.forename: Mike
authors.initials: M
authors.lastname: Clements
mesh_terms: D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D054715:Cardiotoxins / Q000633:toxicity*; D002478:Cells, Cultured; D004566:Electrodes; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects; D005110:Extracellular Space; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000187:drug effects*; D011237:Predictive Value of Tests; D012307:Risk Factors; D013234:Stem Cells / Q000187:drug effects*; D014116:Toxicology / Q000379:methods*
chemical_list: D054715:Cardiotoxins; D051638:Ether-A-Go-Go Potassium Channels; D007473:Ion Channels
keywords: cardiomyocyte; cardiotoxicity; multielectrode array; preclinical; proarrhythmia; stem cell