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

PLoS One. 2024 Sep 27;19(9):e0310463. doi: 10.1371/journal.pone.0310463. eCollection 2024.

Abstract

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.

MeSH terms

  • Arrhythmias, Cardiac* / pathology
  • Cell Differentiation
  • Cell Survival
  • Cells, Cultured
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Myocytes, Cardiac*

Grants and funding

S.P. is funded by the Else-Kröner-Fresenius Stiftung (2019/A84), by the German Society of Internal Medicine, by the German Heart Foundation and by the University of Regensburg (ReForM A program). K.S. and S.S. are funded by the Deutsche Forschungsgemeinschaft (DFG, SO 1223/4-1 and the F. Thyssen Foundation (Az 10.19.2.026MN). S.S. is funded by the Deutsche Forschungsgemeinschaft (DFG, SO 1223/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.