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High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers

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Functional cardiotoxicity profiling and screening using the xCELLigence RTCA Cardio System.

Biao Xi¹, Tianxing Wang, Nan Li

¹ACEA Biosciences, Inc., San Diego, CA 92121, USA. bxi@aceabio.com

Journal of Laboratory Automation

|November 19, 2011

Summary

A new label-free system monitors cardiomyocyte contractility in real-time, aiding preclinical cardiac safety testing. This technology helps identify pro-arrhythmic drug candidates early in development.

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Area of Science:

Cardiovascular pharmacology
Drug discovery and development
Biomedical engineering

Background:

Preclinical cardiac safety assessment is crucial for new drug candidates.
Identifying compounds causing Torsades de Pointes (a fatal arrhythmia) is a key challenge.
Existing methods may lack real-time kinetic information.

Purpose of the Study:

To introduce and validate an innovative label-free, real-time system for monitoring cardiomyocyte contractility.
To assess the system's utility in identifying pro-arrhythmic drug candidates.
To evaluate the potential of impedance-based measurements for mechanistic toxicity information.

Main Methods:

Development of the xCELLigence RTCA Cardio System utilizing impedance measurement.
Assay performed in microtiter plates with integrated gold microelectrodes.
Validation using various cardiomyocyte models (mouse ESC-derived, human iPSC-derived, rat neonatal primary) and known compounds.

Main Results:

The system successfully monitored cardiomyocyte contractility in real-time.
Assay time resolution provided valuable insights into compound action kinetics.
Impedance-based beating profiles offered mechanistic toxicity information and flagged pro-arrhythmic compounds.

Conclusions:

The xCELLigence RTCA Cardio System offers a real-time, kinetic approach to cardiomyocyte contractility assessment.
Beat-to-beat measurement capabilities enhance preclinical cardiac safety evaluation.
This technology is a valuable addition to the drug discovery and development toolkit for cardiac liability assessment.