360 Chapter 13 Study type hiPSC lines (number) hiPSC-CMs maturation status Analysis Assesment Outcome ref. Cardiotoxicity Healthy subjects (11) ~40 days Kinetic high-content contractility analysis ‘Cardiac safety index’ screen of 21 chemotherapeutic kinase inhibitors Good correlation between the in vitro cardiotoxicity and the clinical incidence of cardiotoxicity 63 Cardiotoxicity Healthy subjects (27) ~40 days Ca2+ flux assay, cytotoxicity, TempO-Seq, mitochondrial high content cell imaging Feasibility of hiPSC-CMs as populationbased in vitro model for inter-individual variability hiPSC-CMs can be used to characterize inter-individual responses in untreated and chemical-treated hiPSC-CMs 64 Cardiotoxicity homozygous HLA donors (13) 48 days 1536-well plate dead cell screening, MEA array, TUNEL Screening of 2,375 clinically approved compounds for cardiotoxicity hiPSC-CMs screening confirms known cardiotoxic compounds, and identifies several unknown cardiotoxic compounds. 65 Disease modelling RYR2 (6) TPM1 (2) MYBPC3 (2), KCNQ1(2), HERG (4) LMNA (2) and Healthy subjects (2) ~30-50 days Calcium transients by machine learning Analysis of 12 variables in calcium peaks for the separation of disease vs control Efficient classification accuracy of 87% between the disease group and controls. 66 Disease modelling DMD (4) ~20 days LC–MS, patch clamp, EM, confocal microscopy Study if DMD hiPSC-CM are associated with metabolic deficits DMD hiPSC-CMs recapitulated some disease phenotypes, metoprolol improved myofilament organization 67 Disease modelling TNNT2 (4) 20-50 days Sarcomere distribution, MEA, patch clamp, calcium, contractility analysis Analyze functional properties, describe the potential underlying etiology, and test metoprolol Impairment in myofilament regulation, Ca2+ handling, and force production of individual CMs, explain DCM clinical phenotype 68
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