Simulation of cardiac arrhythmias in human induced pluripotent stem cell-derived cardiomyocytes

by Thea Bommer, Maria Knierim, Julia Unsöld, Dominic Riedl, Laura Stengel, Michael Paulus, Thomas Körtl, Norman Liaw, Lars S. Maier, Katrin Streckfuss-Bömeke, Samuel Sossalla, Steffen Pabel

The effects and mechanisms of cardiac arrhythmias are still incompletely understood and an important subject of cardiovascular research. A major difficulty for investigating arrhythmias is the lack of appropriate human models. Here, we present a protocol for a translational simulation of different types of arrhythmias using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and electric cell culture pacing. The protocol comprises the handling of ventricular and atrial hiPSC-CM before and during in vitro arrhythmia simulation and possible arrhythmia simulation protocols mimicking clinical arrhythmias like atrial fibrillation. Isolated or confluent hiPSC-CM can be used for the simulation. In vitro arrhythmia simulation did not impair cell viability of hiPSC-CM and could reproduce arrhythmia associated phenotypes of patients. The use of hiPSC-CM enables patient-specific studies of arrhythmias, genetic interventions, or drug-screening. Thus, the in vitro arrhythmia simulation protocol may offer a versatile tool for translational studies on the mechanisms and treatment options of cardiac arrhythmias.