In an effort to improve preclinical cardiotoxicity assays, reduce drug testing attrition rates, and ensure drug safety, collaborating scientists at the University Medical Center Utrecht in The Netherlands, and Bioscience Department of AstraZeneca R&D, Molndal, Sweden, have tested Roche’s xCELLigence Cardio Instrument. Their goal was to determine whether impedance recordings are a useful way to detect compound effects on beating frequency of cardiomyocytes, derived either from human induced pluripotent stem cells (hiPS), or from mouse embryonic stem cells (mESC).
The xCELLigence Cardio Instrument is an impedance sensing instrument capable of reading signals at high sampling rates, making it possible to measure the contraction movements of cardiomyocytes in contact with sensor microelectrodes.
In this study(1), the effects of nine compounds were tested on beating frequency (beats per minute, bpm) of hiPS and mESC cardiomyocytes. Jonsson et al reported, “The results of this initial study show that, under the right conditions, the beating frequency of a monolayer of cells can be stably recorded over several days. In addition, the xCELLigence system detects changes in beating frequency and amplitude caused by added reference compounds.”
The authors conclude that xCELLigence Cardio instrument has potential for 96-well-throughput cardiotoxicity screening of the effects of compounds on rhythmic beating patterns of cardiomyocytes. They underscored the 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. They also indicated that the production of distinct subtypes of ventricular, atrial and nodal cardiomyocytes could open up new areas of screening for arrhythmia and cardiotoxicity.
(1) Malin K.B. Jonsson, Qing-Dong Wang, Bruno Becker: Impedance-Based Detection of Beating Rhythm and Proarrhythmic Effects of Compounds on Stem Cell-Derived Cardiomyocytes. ASSAY and Drug Development Technologies. December 2011: 589-599.