Human induced pluripotent stem cell-derived cardiomyocytes as an electrophysiological model: Opportunities and challenges-The Hamburg perspective

Djemail Ismaili; Carl Schulz; András Horváth; Jussi T Koivumäki; Delphine Mika; Arne Hansen; Thomas Eschenhagen; Torsten Christ

doi:10.3389/fphys.2023.1132165

Human induced pluripotent stem cell-derived cardiomyocytes as an electrophysiological model: Opportunities and challenges-The Hamburg perspective

Front Physiol. 2023 Feb 16:14:1132165. doi: 10.3389/fphys.2023.1132165. eCollection 2023.

Authors

Djemail Ismaili^{1

2

3}, Carl Schulz^{1

3}, András Horváth⁴, Jussi T Koivumäki⁵, Delphine Mika⁶, Arne Hansen^{1

3}, Thomas Eschenhagen^{1

3}, Torsten Christ^{1

3}

Affiliations

¹ Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
² Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³ DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
⁴ Translational Cardiology, Department of Cardiology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland.
⁵ BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁶ Inserm, UMR-S 1180, Université Paris-Saclay, Orsay, France.

Abstract

Models based on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are proposed in almost any field of physiology and pharmacology. The development of human induced pluripotent stem cell-derived cardiomyocytes is expected to become a step forward to increase the translational power of cardiovascular research. Importantly they should allow to study genetic effects on an electrophysiological background close to the human situation. However, biological and methodological issues revealed when human induced pluripotent stem cell-derived cardiomyocytes were used in experimental electrophysiology. We will discuss some of the challenges that should be considered when human induced pluripotent stem cell-derived cardiomyocytes will be used as a physiological model.

Keywords: action potentials; automated patch clamp; computer modelling and simulation; hESC-CM; hiPSC-CM; human cardiomyocytes; ion currents.

Publication types

Review

Grants and funding

This study was supported by the German Ministry of Education and Research (BMBF, FKZ161L0236), by the German Centre for Cardiovascular Research (Grant No. 81Z0710110 to CS), European Research Council (ERC-AG IndivuHeart), Deutsche Forschungsgemeinschaft (DFG Es 88/12-1, DFG HA 3423/5-1), the Freie und Hansestadt Hamburg and the Fédération Française de Cardiologie (to DM).