Project 462843

Heart failure has a universally poor outcome, with only 50% of patients surviving a further five years after diagnosis. The medications that are available for heart failure have little impact on patient survival, mostly targeting the control of disease symptoms. Regenerative medicine, where the heart is promoted to repair itself, is a new, potentially disruptive, treatment paradigm that could provide lasting change to organ function. In determining how this concept could be harnessed for benefit, we and others have described how the hearts of very young patients (neonates) have a higher intrinsic ability to repair and regenerative themselves. Using tissue samples from pediatric patients undergoing open heart surgery, we have found that cells with regenerative potential (stem cells) isolated from neonatal hearts secrete different molecules than cells isolated from older patients. We now propose to harness this capacity into a novel biologic therapy for heart failure patients. We have collected and characterized the secreted molecules from the cardiac stem cells of young patients, finding five key proteins that are able to induce heart repair in a model of heart failure due to poor blood flow (heart attack). In this proposal, we will determine the dose and timing of therapeutic cocktail administration. In a large animal model (pig) we will perform advanced analysis that will directly provide translation to a clinical trial. This work will create a new paradigm of treatments for heart failure, allowing for meaningful improvements to patient outcome.