Combined Impedance and Extracellular Field Potential Recordings from Human Stem Cell-Derived Cardiomyocytes
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Measurement of contractility using impedance is a novel method for gaining information about a drug candidate’s potential to disturb cardiac cell contraction. The impedance signal is recorded from a monolayer of cardiac cells, most commonly derived from human-induced pluripotent stem cells (hiPSCs), which are becoming an attractive model for safety testing, especially in the light of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative introduced in 2013. The goal of this initiative is, in part, to standardize assays, targets, and cell types but also to evaluate the potential of new technologies, in this context, such as impedance. The CardioExcyte 96 is a hybrid system that combines the impedance readout (a measure of cell contractility) with extracellular field potential (EFP) recordings. This chapter focuses on cell handling of hiPSC cardiomyocytes (CMs) and the short- and long-term investigation into pharmacological effects of a wide range of pharmacological agents, including flecainide, nifedipine, isoproterenol, and E4031 using the CardioExcyte 96.
Key wordsCardioExcyte 96 CiPA initiative Early after-depolarizations Extracellular field potential hERG hiPSC-derived cardiomyocytes Impedance Label-free Safety pharmacology
We thank Cellular Dynamics International (CDI), Madison, Wisconsin, for the collaboration and for providing us with cardiomyocytes (iCell cardiomyocytes). We also thank Axiogenesis AG, Cologne, Germany, for the collaboration and for providing us with cardiomyocytes (Cor.4U). We also thank Pluriomics for the collaboration and for providing us with the Pluricytes.
The authors disclose receipt of the following financial support for the research, authorship, and/or publication of this article: The work presented here was funded in part by the Bayerische Forschungsstiftung (BayFor, Grant AZ-1036-12) and by the Bundesministerium für Bildung und Forschung (BMBF, Grant 01QE1502).
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