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Roche's xCELLigence RTCA Cardio Instrument Used to Estimate the Risk of Drug-induced Proarrhythmia in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes
Using the Roche xCELLigence Cardio Instrument, they discovered that changes in cell impedance of stem cell derived cardiomyocytes treated with different compounds were comparable to results from more established low throughput in vitro technology (e.g., measuring electric field potentials via microelectrode arrays).
The xCELLigence Cardio System uses proprietary software and E-Plates 96 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.
Kolaja and his team calculated an index of drug-induced arrhythmias based on the cytotoxic effects of the drugs tested, enabling the calculation of a given drug's "predicted proarrhythmic score" (PPS), a measure of potential cardiotoxicity. According to Kolaja, "We found that measuring impedance provides a rapid means of interrogating a drug's deleterious effect on human cardiac function, and not only helps us in early discovery safety assessment, but opens up new opportunities for investigating, cardiac biology, cell signaling and disease pathogenesis. More importantly, human pluripotent stem cell-based predictive toxicity assays will help researchers predict potential safety issues of promising drug candidates early in the development process and provide insight into the mechanisms of drug-induced organ toxicity."
The authors of this study raise the possibility that this new model system may be amenable to high throughput approaches that go beyond hERG mediated-QT prolongation and delve directly in the functional interplay of the many ion channels used by human heart muscle to affect normal function.
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