Impedance-Based Cell Analyzer Scores in Cardiotoxicity Pilot Study

A cellular assay system that measures electronic impedance was used in a pilot study that examined the effect of several drug compounds on the behavior of cultures of cardiomyocytes, derived either from human induced pluripotent stem cells (hiPS), or from mouse embryonic stem cells (mESC).

Investigators at the University Medical Center (Utrecht, the Netherlands) and their collaborators at the Bioscience Department of AstraZeneca R&D (Mölndal, Sweden) worked with the Roche (Basel, Switzerland) xCELLigence Cardio instrument.

The xCELLigence Cardio instrument is powered by proprietary software and employs 96-well E-plates to measure electronic cell impedance using sensor electrodes. Computer-controlled signal generation, automatic frequency scanning, and a measurement rate of 12.9 milliseconds per 96-well plate, enable high-speed precise detection of changes in cardiac cell behavior.

The aim of the current study was to test whether impedance readings could be a useful tool to detect the effects of candidate drug compounds on beating frequency (beats per minute, bpm) and arrhythmias of human induced pluripotent stem cell- and a mouse embryonic stem cell-derived cardiomyocyte line.

Results published in the December 7, 2011, issue of the journal Assay and Drug Development Technologies revealed that under the correct conditions, the beating frequency of a monolayer of cells could be recorded stably over a period of several days. Additionally, the system detected changes in beating frequency and amplitude caused by added reference compounds.

The investigators concluded that, “The xCELLigence Cardio instrument has potential for 96-well-throughput cardiotoxicity screening of the effects of compounds on rhythmic beating patterns of cardiomyocytes. There is a need for continuous improvements in the maturation of available cardiomyocytes and in further validation of the assay on an extended set of reference compounds with known in vivo effects. The production of distinct subtypes of ventricular, atrial, and nodal cardiomyocytes could open up new areas of screening for arrhythmia and cardiotoxicity.”

Related Links:
University Medical Center
AstraZeneca R&D
Roche