Generation of hypertrophic cardiomyopathy using human induced pluripotent stem cells
October 2015
Leiden University Medical Center, Leiden, Netherlands
Human pluripotent stem cells (hPSCs) are becoming increasingly used in biomedical research on heart disease and drug-associated toxicity. Yet the baseline functional performance of these cells is still less than that in adult heart tissue. In the present study, the researchers aimed at identifying factors that would promote adequate contractility measurements in a hiPSC model of hypertrophic cardiomyopathy (HCM). Cells were isolated from donors and differentiated into cardiomyocytes in vitro. The cells were then treated with combinations of known cardiac modulators to screen for compounds that could improve the electrophysiological profile of hiPSC-CMs. Using the identified ideal combination of compounds, the cells were then modified to express mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM. The cells expressing mutant MYBPC3 indeed showed lower contractility. This model should be further used to identify therapeutic agents.
Contractile defect caused by mutation in MYBPC3 revealed under conditions optimized for human PSC-cardiomyocyte function
Christine L. Mummery
Added on: 11-30-2021
[1] https://www.cell.com/cell-reports/fulltext/S2211-1247(15)01036-0[2] https://data.jrc.ec.europa.eu/dataset/20947a04-86ef-473f-8907-c658e4050c24
