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Stem cell‐derived cardiomyocyte heterogeneity confounds electrophysiological insights
Journal Title
The Journal of Physiology
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Journal Title
Term and Year
Publication Date
2024-05-09
Book Title
Publication Volume
602
Publication Issue
20
Publication Begin
5155
Publication End
5162
Number of pages
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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.
Citation
Clark AP, Krogh-Madsen T, Christini DJ. Stem cell-derived cardiomyocyte heterogeneity confounds electrophysiological insights. J Physiol. 2024 Oct;602(20):5155-5162. doi: 10.1113/JP284618. Epub 2024 May 9. PMID: 38723234; PMCID: PMC11493526.