Collection of tissue samples for the study of cardiac hypertrophy and simultaneous functional profiling of the diseased hearts to allow later validation of iPSC-derived in vitro models
Cardiac hypertrophy is a common manifestation of cardiovascular disease which results in the thickening of the cardiac wall reducing the ability of the heart to contract and efficiently pump blood throughout the body. The disease frequently results in heart failure and death. Most of our understanding of cardiac hypertrophy is derived from animal models that do not faithfully replicate the human disease. Cardiac hypertrophy is the results of complex interactions between genetic, epigenetic and metabolic factors. Current therapies have provided only limited benefit and there is tremendous need to understand this pathology in the hearts of patients with hypertrophy so that more effective therapies can be developed.
The derivation of pathological cells and tissues through the in vitro differentiation of iPSC is a very promising approach. A key challenge remains the validation of the iPSC-derived cells with evidence that they are truly equivalent to the patient's tissue and constitute a useful model for experimenting new therapies. [REDACTED] specializes in the recovery of non-transplantable human hearts from organ donors and routinely tests the activity of new drug candidates on human hearts. Collecting samples from organ donors with or without cardiac hypertrophy, [REDACTED] will provide fibroblasts and cardiac progenitor cells for iPSC derivation. In addition the donors' hearts will be tested to generate data that will constitute a valuable reference for researchers.
California will benefit from this project in three ways: new and more effective therapies to treat heart failure, increased access to advanced research tools for California institutions and now jobs to the State in the fields of cardiovascular research and drug discovery. Heart disease and stroke are the number one and number three causes of death respectively, and a leading cause of disability, among Californians. Compared to the rest of the States in the Nation, California has slightly above average rates for coronary heart disease and stroke mortality. The establishment of a California-based repository of human iPSC derived from patients with cardiac disease and with an associated database of cellular physiological will create an unparalleled tool for the advancement of understanding of cardiac disease. The new knowledge will translate into increased intellectual property for the participating institutions in California. Furthermore a better understanding of the pathology will uncover novel potential therapeutic targets and stimulated efforts in drug discovery for the treatment of heart failure. These efforts will likely result in new high-tech drug discovery jobs.