Key result
Mechanical resistance reveals HCM hallmarks in MYBPC3-mutated iPSC-cardiomyocytes absent in standard 2D culture.
Why the study?
HCM exhibits variable penetrance and hypertension causes major morbidity in patients with HCM, suggesting nongenetic mechanical stress may interact with sarcomeric mutations to trigger the disease phenotype.
Population
iPSC-derived cardiomyocytes bearing MYBPC3 loss-of-function mutations engineered into micro-heart muscle arrays (μHM)
Comparison
Contractile mechanical resistance across substrate stiffnesses from 0.4 kPa to 114 kPa vs standard 2D culture
Design
In vitro physiological engineered tissue study
Authors
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May advance in vitro HCM modeling; leaves open in vivo validation and clinical translation.
An engineered 3D micro-heart muscle model incorporating mechanical afterload successfully unmasks hypertrophic cardiomyopathy phenotypes in MYBPC3-mutant iPSC-cardiomyocytes that remain hidden in standard 2D cultures.
Guo et al. (2023) studied Hypertrophic cardiomyopathy. Mechanical resistance (substrate stiffness 0.4 kPa to 114 kPa) vs. Standard 2D culture was evaluated on Disease pathology hallmarks (cellular hypertrophy, impaired contractile energetics, maladaptive calcium handling). Subjecting iPSC-derived cardiomyocytes with MYBPC3 mutations to mechanical resistance revealed hallmarks of hypertrophic cardiomyopathy, including cellular hypertrophy, absent in standard 2D culture.
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