Grant: Doctoral Research Award: Canada Graduate Scholarships

Heart valve replacement surgery is one of the most common operations performed by cardiac surgeons. There are only two main valve options offered to patients today: mechanical and bioprosthetic valves, both options have significant limitations. Mechanical valves are limited by the need for life-long blood thinners. Bioprosthetic valves constructed out of animal tissue are limited by valve failure over a patient's lifetime. Our research project seeks to remedy this issue by creating a tissue-engineered heart valves (TEHV) that do not need blood thinners nor undergo valve failure. Our lab has previously shown that bioprosthetic valves undergo a significant immune rejection once they are implanted in our bodies. This immune rejection contributes significantly to valve failures. Tissue engineering is a solution to prevent this immune rejection. It is a process that removes animal cells from bioprosthetic valves and then reseeds human stem cells to attenuate the culprit immune rejection. In our preliminary studies using autogeneic stem cells (subject's own cells), we showed a reduction in immune reaction in TEHV in small animal models and in in-vitro models. We now seek to further our work in three main ways. One, determine whether allogeneic stem cell (different subject, same species) repopulation of TEHV can limit the immune rejection in a long-term in-vivo large animal model where we implant sheep's TEHV into a pig's aorta to assess the immune function. Two, similar immune rejection analyses in a long-term in-vivo small animal model with guinea pig TEHV into a rat's aorta and assess the immune function. These two experiments mimic bioprosthetic valve implantation in humans. Three, assess the immune response to allogeneic stem cells TEHV in a human in-vitro model where we expose TEHV to the human whole blood and assess immune rejection. Taken together, these studies will demonstrate whether TEHV can successfully reduce immune rejection and prevent valve failure.