Evaluation of cellular impedance measures of cardiomyocyte cultures for drug screening applications

Assay and Drug Development Technologies
Matthew F PetersYvonne P Dragan

Abstract

Cardiovascular toxicity is a leading contributor to drug withdrawal and late-stage attrition. Earlier and broader screening is a validated approach to build-in cardiovascular safety as demonstrated with human Ether-à-go-go-related gene (hERG) screening to reduce drug-induced arrhythmia. There is an urgent need for novel in vitro assays to address other mechanistic aspects of cardiovascular function, including contractility, heart rate, toxicity, hypertrophy, and non-hERG arrhythmia. Recent advances in label-free cellular impedance technology now enable tracking of spontaneous, synchronized beating of cultured cardiomyocytes. Analysis of beating allows integrated detection that is downstream of electrical and mechanical aspects of contraction. Here, we evaluate impedance-based cardiomyocyte responses against criteria required for drug screening. The throughput and sensitivity allowed for rapid assay development. Critical variables for rat neonatal cardiomyocyte assays included cell density and serum levels. Once optimized, consistent, stable beating for at least 3 days was straight-forward to achieve. In tests of compounds spanning a breadth of target classes, the potency values showed excellent precision, wide dynamic range, an...Continue Reading

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Citations

Jul 31, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sarah D LamoreMatthew F Peters
Sep 21, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Liang GuoKyle L Kolaja
Mar 9, 2013·Toxicology Letters·Clay W ScottYvonne P Dragan
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Jun 19, 2015·Open Biology·J RotherM Tarantola
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Sep 23, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Clay W ScottMatthew F Peters
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