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

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

Djemail Ismaili  1   2   3 , Carl Schulz  1   3 , András Horváth  4 , Jussi T Koivumäki  5 , Delphine Mika  6 , Arne Hansen  1   3 , Thomas Eschenhagen  1   3 , Torsten Christ  1   3
Affiliations
Review

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

Djemail Ismaili et al. Front Physiol. .

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.

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Conflict of interest statement

TE and ArH were co-founders of EHT Technologies GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor YE declared a past co-authorship with the author TE.

Figures

FIGURE 1
FIGURE 1
Similarities and differences in action potential shapes between adult human heart tissue and engineered heart tissue based on hiPSC-CM. Typical original traces of action potentials (AP) recorded in human adult (left) and engineered heart tissue (EHT, right) from atrium (top) and ventricle (bottom). Same scaling and zero voltage level for all four pictures. Differences in ion currents are indicated with red letter with + or − indicating changes related to adult tissue. Ion currents within the same range are indicated in green letter. Letters are given in brackets for ion currents where differences are suspected from AP recordings (no direct comparison of patch clamp data). Abbreviations: I Ca,L, L-type Ca2+-current; I Ca,T, T-Type Ca2+-current; I f, hyperpolarization-activated funny current; I K,ACh, Acetylcholine-activated potassium current; I Ks, slow delayed rectifier potassium current; I Kur, ultrarapidly activating potassium current; IK1, inward rectifier potassium current; I Na, sodium current; I NCX, Na+/Ca2+-exchanger.
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