733-3 Successful Transplantation of Myoblasts into Adult Porcine Myocardium: A Potential Method to Repair a Failing Heart

The profound shortage of organ donors continues to fuel the search for other methods to refurbish a failing heart. The use of transgenic cells transplanted (Tx) in syngeneic rodents has shown modest success, but allogeneic and xenogeneic transplants have not been uniformly successful. To assess the feasibility of xenogeneic and allogeneic myoblast transplantation, six adult swine underwent transplantation of murine atrial tumor cells (Xenogeneic) and neonatal porcine myocytes (Allogeneic) into the left ventricular wall. Following general anesthesia, isolated cells were injected along the anterior and posterior wall ofthe porcine left ventricle (six sites per animal). All the animals were immunosuppressed with cyclosporine and prednisone and were followed for 1 month post-injection and then sacrificed. Results are as follows: In all 36 injected sites, the Tx cells proliferated within the host myocardium with no significant rejection. CPK MB did not increase after the procedure indicating that there was no damage to the host myocardium from the injection of cells. Moreover, Tx cells formed close associations with host myocytes that resembled intercalated discs on electron microscopy, and were composed of PAN cadherin on immunofluorescent staining. These cells also contained myofibrils and other cell architecture that resembled normal AT-l or neonatal myocytes. Additionally, these cells produced angiogenic factors resulting in a proliferation of the surrounding microvasculature. In conclusion, these findings indicate successful xenogeneic and allogeneic myocyte cell transplantation in a large animal model. These experiments set the stage for future studies testing the ability of these cells to form a syncitium, contract, and thereby “repair” a damaged heart