Monitoring Cardiomyocyte Functional Indices with Hybrid Mea-Impedance Technology

Abstract

The recent progress in biosensor technology combined with availability of human stem cell-derived cardiomyocytes (SC-CMs) provides an exciting possibility to assess novel biomarkers of cardiac function in vitro. CardioExcyte 96 (Nanion Technologies GmbH, Germany) is a new screening platform combining impedance and extracellular field potential (EFP) recordings, which allows label-free simultaneous assessment of electrical activity, beating and electromechanical coupling in a variety of multi-cellular cardiac preparations.The goal of the present study was to evaluate the utility of the new hybrid instrument for multi-parameter profiling of endogenous responses in human SC-CMs. Cor.4U iPS-derived cardiomyocytes (Axiogenesis, Germany) cultured over a week were treated with reference drugs from various pharmacological classes affecting cardiac ion channels, pumps, adrenergic receptors and intercellular communication to evaluate their effect on various parameters of impedance and EFP signals. In addition to the pharmacological effects, dynamics of the cell growth and development in culture were monitored to derive an analytical expression for the system. Detailed investigation of the cellular beat signal facilitated multi-parameter evaluation allowing integrative assessment of cardiomyocyte behavior. The resulting multiplex signatures can be used as a fingerprint tool to highlight changes in cardiac function and potentially to categorize drugs based on their mechanisms of action.The hybrid impedance-EFP measurements in human SC-CMs exemplify a novel screening method for early and sensitive multi-parameter profiling in vitro. This integrative approach meliorates the screening pipeline by bridging single cell-based assays and ECG measurements for translational assessment.