Leducq Network of Excellence

Program Title: Xenogenic and Exogenic Pig Organs for Transplantation into Humans

Advanced heart failure is common, deadly and warrants novel therapies. The only curative therapy is cardiac allotransplantation but it is limited due to the shortage of donor organs. Using genetically engineered pigs, the long-range goals and clinical significance of this proposal are to engineer and compare the function and immunogenicity of a porcine cardiac xenograft that has selective vs. a completely humanized vasculature. These humanized hearts will be evaluated as an unlimited source of organs for cardiac transplantation and provide a paradigm shifting platform for the treatment of end-stage heart failure. The publications and our preliminary data provide the rationale and the feasibility for the proposed experimental strategy. Further, we have assembled an outstanding international team of experts that will provide complementary expertise in order to accelerate our research and amplify our efforts to achieve our research goals. In these studies, we will use complementary strategies to compare pig hearts with specific gene deletions and expression of selected human transgenes versus pig hearts with a completely humanized vasculature (via blastocyst complementation using hiPSCs). The resulting gene edited pigs and chimeric pigs will revolutionize the field of cardiac transplantation by providing unlimited donor sources for hearts that will be transplanted into patients with end-stage heart failure. The complementary areas of expertise of the network members will allow for unprecedented synergies that will result in paradigm shifting discoveries. Further, the training opportunities, within this network, will not only build research careers but also promote collaborative interactions resulting in an acceleration of discoveries emerging from the network. The potential impact of this network proposal is tremendous.