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Review
. 2024 Oct;602(20):5155-5162.
doi: 10.1113/JP284618. Epub 2024 May 9.

Stem cell-derived cardiomyocyte heterogeneity confounds electrophysiological insights

Alexander P Clark  1 , Trine Krogh-Madsen  2   3 , David J Christini  1   4
Affiliations
Review

Stem cell-derived cardiomyocyte heterogeneity confounds electrophysiological insights

Alexander P Clark et al. J Physiol. 2024 Oct.

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer potential as an in vitro model for studying drug cardiotoxicity and patient-specific cardiovascular disease. The inherent electrophysiological heterogeneity of these cells limits the depth of insights that can be drawn from well-designed experiments. In this review, we provide our perspective on some sources and the consequences of iPSC-CM heterogeneity. We demonstrate the extent of heterogeneity in the literature and explain how such heterogeneity is exacerbated by patch-clamp experimental artifacts in the manual and automated set-up. Finally, we discuss how this heterogeneity, caused by both intrinsic and extrinsic factors, limits our ability to build digital twins of patient-derived cardiomyocytes.

Keywords: digital twin; electrophysiology; experimental artifact; iPSC‐CM; patch clamp; systems biology.

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References

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