Kinetic Image Cytometry For Predicting Arrhythmias Using Human Stem Cell-Derived Cardiomyocytes

Kinetic Image Cytometry (TM) (KIC (TM)), in which living cells are cultured in multi-well dishes and imaged for electrophysiological transients (such as intracellular calcium or membrane potential) using automated digital microscopy/image analysis, represents an advance in the field of high content analysis. KIC methods, coupled with the use of human stem cell-derived cardiomyocytes (hSC-CMs), are potentially very useful for identifying proarrhythmia activity of test compounds, relevant to cardiosafety. In the present study, a panel of 40 compounds was tested with KIC to quantify the effects of the chemicals on the calcium transients associated with contraction in hSC-CMs, and the results compared to the effects of these compounds on the QT-interval from human electrocardiograms. The kinetics of the calcium transients quantified with KIC identified the chemicals that prolong (commonly associated with proarrhythmic activity) or shorten the QT interval with 100 % specificity and 94 % sensitivity. These data, along with data obtained in previous studies utilizing KIC and hSC-CMs, demonstrate that this assay platform represents the current "state-of-the-art" in vitro method for testing drug candidates for proarrhythmic tendencies.