Table 1 Examples of currently published human induced pluripotent stem cell-derived cardiomyocyte disease models
Cardiovascular disease category | Cardiovascular disease modeled with hiPSC-CMs | Phenotype observed/recapitulated in vitro | Drug treatment to rescue phenotypes | Reference |
|---|---|---|---|---|
Cell signaling defect | LEOPARD syndrome | Cardiomyocyte hypertrophy, NFATC4 nuclear accumulation, increase in RAS/MAPK phosphorylation | NA | [28] |
Channelopathy | Long QT syndrome 1 | Drug-induced prolongation of field potential duration | NA | [40] |
Channelopathy | Long QT syndrome 1 | Cardiac action potential prolongation, irregularities in potassium-gated voltage channel (KCNQ1) localization | Propranolol | [33] |
Channelopathy | Long QT syndrome 2 | Cardiac action potential prolongation | Pinacidil, nifedipine, ranolazine | [41] |
Channelopathy | Long QT syndrome 2 | Prolonged field and action potential, drug-induced early after depolarizations | Nicorandil, nadolol, propranolol | [42] |
Channelopathy | Long QT syndrome 2 | Prolonged action potential duration, increased sensitivity to arrhythmogenic drugs | NA | [43] |
Channelopathy | Long QT syndrome 3 | Prolonged action potential duration, early after depolarization, sodium current irregularities | NA | [44] |
Channelopathy | Long QT syndrome 3 | Sodium current irregularities, longer action potential duration | NA | [45] |
Channelopathy | Long QT syndrome 3 | Sodium current irregularities, prolonged QT interval | NA | [46] |
Channelopathy | Long QT syndrome 8, Timothy syndrome | Anomalous calcium transients, cardiac action potential prolongation, irregular cardiomyocyte contraction | Roscovitine | [47] |
Channelopathy | CPVT-1 | Intracellular calcium concentration irregularities, delayed after depolarizations | Dantrolene | [48] |
Channelopathy | CPVT-1 | Abnormal calcium release, abnormal calcium response after phosphorylation, anomalous calcium transients | NA | [49] |
Channelopathy | CPVT-1 | Abnormal calcium transients, early after depolarizations, reduced sarcoplasmic reticulum calcium concentration | NA | [50] |
Channelopathy | CPVT-1 | Delayed after depolarizations, calcium transient irregularities, abnormal calcium concentrations | Flecainide, thapsigargin | [51] |
Cardiomyopathy caused by structural/sarcomeric protein mutation | CPVT-2 | Isoproterenol-induced delayed after depolarizations, abnormal calcium concentrations, myofibril disorganization, sarcoplasmic reticulum abnormalities | NA | [32] |
Cardiomyopathy caused by structural/sarcomeric protein mutation | Familial dilated cardiomyopathy | Reduced force output during cardiomyocyte contraction, sarcomeric structural irregularities, abnormal beating rate, abnormal calcium transients | Metoprolol | [52] |
Cardiomyopathy caused by structural/sarcomeric protein mutation | Familial hypertrophic cardiomyopathy | Enlarged hiPSC-CM phenotype, elevated intracellular calcium levels, irregular calcium transients | Verapamil | [53] |
Cardiomyopathy caused by structural/sarcomeric protein mutation | ARVD/C | Reduced expression of plakophilin-2, increase in intracellular lipid levels, disorganized hiPSC-CM sarcomeric structure | Nifedipine, isoproterenol | [54] |
Cardiomyopathy caused by structural/sarcomeric protein mutation | ARVD/C | Irregular plakophilin-2 nuclear accumulation, diminished β-catenin activity in cardiogenic conditions, abnormal peroxisome proliferator-activated receptor gamma activation, calcium handling defects | NA | [55] |
Cardiomyopathy caused by structural/sarcomeric protein mutation | Pompe disease | High glycogen levels, ultrastructural abnormalities, cellular respiration irregularities | I-carnitine, acid alpha-glucosidase | [56] |