359 General Discussion - hiPSC-CMs Disease Modelling and Future Perspectives 13 Table 1. Overview of all studies using four or more hiPSC-lines for cardiac drug response, toxicity, and disease modeling in vitro. Study type hiPSC lines (number) hiPSC-CMs maturation status Analysis Assesment Outcome ref. Drug response Healthy subjects (10) ~50 days (EHTs) Contractile parameters, RNA Nanostring analysis Screening of 7 inotropic indicator compounds. Baseline phenotypes of healthy control cell lines differ considerably, drug responses were qualitatively similar. 57 Drug response RyR2 (6) ~30-50 days Calcium transients by machine learning Anti-arrhythmic effect of dantrolene after adrenaline administration Classification accuracy of 65.6% and sensitivities (true positive rates) of 79.7% for responders 58 Drug response Healthy subjects (6) Qualitative differences in action potentials 8 different classes of pharmacological reagents Female iPSC-CMs more sensitive to dofetilide/ cisapride. Male hiPSC-CMs less sensitive to two hERGs. Some donor hiPSC-CMs showed different responses to drugs and external stimulation. 59 Cardiotoxicity Healthy subjects (10) ~40 days MEA array (FPD), RNA Microarray Risk of moxifloxacininduced long QT in patients vs. hiPSC-CMs Significant correlation of FDP response to the inter-individual differences observed in vivo 60 Cardiotoxicity Healthy subjects (14) ~50 days MEA array (FPD), patch-clamp analysis, RNAseq Risk prediction in hiPSC-CMs from patients with low (7) or high (7) sensitivities to Sotalol-induced long QT Strong correlation of FDP response to the interindividual differences observed in vivo 61 Cardiotoxicity Healthy subjects (16) ~30 days APD recordings (CellOPTIQ) Risk of dofetilide or moxifloxacininduced long QT in patients vs. hiPSC-CMs. No significant correlation between the in vitro hiPSC-CM and the clinical response of the same subject 62
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