Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is a genetic disorder that affects cardiac desmosomes, cell-to-cell attachment, and electrophysiological function. The parent grant ?ARVD/C Dysfunction in Human Stem Cell-Derived Cardiac Tissuee? uses, as a model of the cardiac disease, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) that are grown to form engineered heart slices (EHS). The goal of this supplemental research is to provide a more faithful rendition of ARVC-EHS to the later stages of the disease in which myocytes have been replaced by fatty tissue. Therefore, the specific aim of the research is to investigate the effects of adipocytes (fat generating cells) on ARVC cardiomyocytes in a tissue context. The adipocytes will be obtained by culturing adipose-derived stem cells in adipogenic media, which will then be added to ARVC-EHS at one of two different time points. Various combinations of culture conditions will be tested, and the likelihood of arrhythmia will be assessed through electrophysiological testing.
Capturing the hallmarks of human cardiac disease into cellular models is very challenging, but essential for the forward progress in understanding the pathological consequences of the disease as well as potential therapies. This project will improve the fidelity of our engineered ?disease-in-a-dish? model of an inheritable cardiac disease that makes young athletes highly prone to sudden cardiac death.
