Grant: Collaborative Health Research Projects (NSERC partnered)

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 preliminarily characterized an initial set of samples from pediatric heart surgery patients. In this project, we will expand our analysis to include a broader range of patient age and cardiac diagnosis. The secreted mixtures will be tested for regenerative potential in established assays, and their composition determined, illuminating the components with the highest therapeutic potential. Using a novel biocompatible scaffold invented by a member of our collaborative group, we will create an optimal delivery vehicle for injection into the failing hearts of patients, allowing for sustained release of the reparative molecules. Finally, we will test the utility of the new therapies in a large animal model of heart failure. We will work in close collaboration with our industry partner, Bluerock Therapeutics, whose sole mandate is to bring regenerative therapies to market, allowing for immediate commercial application and translation into patient care.