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arXiv · 2505.20775

Non-invasive maturity assessment of iPSC-CMs based on optical maturity characteristics using interpretable AI

Fabian Scheurer·Alexander Hammer·Mario Schubert·Robert-Patrick Steiner·Oliver Gamm·Kaomei Guan·Frank Sonntag·Hagen Malberg·Martin Schmidt
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Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are an important resource for the identification of new therapeutic targets and cardioprotective drugs. After differentiation iPSC-CMs show an immature, fetal-like phenotype. Cultivation of iPSC-CMs in lipid-supplemented maturation medium (MM) strongly enhances their structural, metabolic and functional phenotype. Nevertheless, assessing iPSC-CM maturation state remains challenging as most methods are time consuming and go in line with cell damage or loss of the sample. To address this issue, we developed a non-invasive approach for automated classification of iPSC-CM maturity through interpretable artificial intelligence (AI)-based analysis of beat characteristics derived from video-based motion analysis. In a prospective study, we evaluated 230 video recordings of early-state, immature iPSC-CMs on day 21 after differentiation (d21) and more mature iPSC-CMs cultured in MM (d42, MM). For each recording, 10 features were extracted using Maia motion analysis software and entered into a support vector machine (SVM). The hyperparameters of the SVM were optimized in a grid search on 80 % of the data using 5-fold cross-validation. The optimized model achieved an accuracy of 99.5 $\pm$ 1.1 % on a hold-out test set. Shapley Additive Explanations (SHAP) identified displacement, relaxation-rise time and beating duration as the most relevant features for assessing maturity level. Our results suggest the use of non-invasive, optical motion analysis combined with AI-based methods as a tool to assess iPSC-CMs maturity and could be applied before performing functional readouts or drug testing. This may potentially reduce the variability and improve the reproducibility of experimental studies.

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Fabian Scheurer, Alexander Hammer, Mario Schubert, Robert-Patrick Steiner, Oliver Gamm, Kaomei Guan, Frank Sonntag, Hagen Malberg, Martin Schmidt. 2025-05-27. Non-invasive maturity assessment of iPSC-CMs based on optical maturity characteristics using interpretable AI. https://doi.org/10.1016/j.csbj.2025.08.024

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