Key result
Electrophysiological heterogeneity in iPSC-CMs confounds in vitro modeling and patient-derived digital twin development.
Why the study?
Human induced pluripotent stem cell-derived cardiomyocytes offer potential for studying drug cardiotoxicity and cardiovascular disease, but their inherent electrophysiological heterogeneity limits experimental insights.
iPSC-CM electrophysiological heterogeneity and automated patch-clamp artifacts confound in vitro cardiac modeling, requiring fully-integrated computational models that incorporate artifact equations to improve precision cardiology efforts.
Answers are grounded in this paper and cite their sources.
Heterogeneity in iPSC-CMs warrants caution interpreting in vitro cardiotoxicity data; leaves open reliable patient-derived digital twins without artifact-adjusted models.
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.
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Clark et al. (2024) reported a review. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) was evaluated. Inherent and experimental electrophysiological heterogeneity in iPSC-CMs confounds in vitro insights and limits the ability to build patient-derived digital twins.
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