In Vitro Physiological Model Developed to Study Hypertrophic Cardiomyopathy

Scientists at Washington University in St. Louis have developed a novel approach to studying hypertrophic cardiomyopathy (HCM), a potentially fatal heart condition. By manipulating stem cells to behave like mature heart cells, researchers can now investigate the disease's mechanisms without relying on animal models or short-lived human heart cells.

The team, led by Nathaniel Huebsch and Jonathan Silva, used induced pluripotent stem cell (iPSC)-derived cardiomyocytes to replicate the behavior of adult heart cells carrying the HCM mutation. This breakthrough allows for extended study of the disease process, overcoming the limitations of traditional research methods.

To achieve this, the team subjected stem cells to mechanical stresses, simulating the conditions experienced by heart cells in a functioning muscle. This "bootcamp" approach enabled the cells to mimic mature heart cell behavior more accurately.

The research, published in iScience, revealed that the HCM mutation affects the myofilament structure, altering calcium shuttling within the cell. This disruption makes the cell more susceptible to arrhythmia, explaining the unexpected electrical issues observed in HCM patients despite the mutation being in mechanical genes.

"It's like the lights go out even though you have a plumbing problem," Silva explained, highlighting the complex relationship between mechanical and electrical functions in the heart.

This innovative approach opens new avenues for understanding and potentially treating HCM. The researchers plan to use computational tools to identify specific calcium channels affected by the mutation and explore various interventions to predict patient outcomes.