The human heart has little capacity to repair or regenerate, and following the myocardial infarction injury the myocardium is replaced by non-contracting scar tissue.
Consequently, increased wall stress and workload on the remaining myocardium leads to chamber dilation, dysfunction, and ultimately heart failure.
Cardiovascular Regeneration (Nicolas Christoforou)
Despite modern therapeutic advances, many patients progress to advanced disease stage with high mortality rates. Cell-based therapy offers the potential of reversing this process by replacing the damaged myocardium with functional cells. The success of such an approach depends on: the choice of an appropriate cell source with the capacity to form cardiomyocytes and vasculature, the efficiency of cell donor delivery, and the absence of side effects such as tumor formation and arrhythmias. Currently the majority of cell-based cardiac therapies primarily focus on the differentiation capacity of the donor cell. Neglect of the delivery aspect leads to low cell survival, low retention, and inadequate donor cell distribution in the myocardium. We propose to utilize a combination or cells, hydrogel biomaterials, and macromolecules in order to effectively achieve the regeneration of the ailing myocardium.
Recreation of the arterial wall (Jeremy Teo)
One of the main challenges of cardiovascular regenerative medicine is the development of therapeutic strategies that enhance the regeneration of both functional muscle and vasculature in the failing heart. We propose to in vitro assemble 3-dimensional cardiac tissue constructs capable of organized vascularization by combining cell types in an environment that mimics the native myocardial cellular composition. These constructs in turn will be tested for their capacity to functionally electromechanically couple with the host ailing myocardium in an in vivo model of cardiovascular disease.