The major goal of this project is to improve the performance of intravascular prosthetic devices by seeding these devices with genetically altered endothelial cells. Failure of intravascular prostheses due to thrombosis and neointimal hyperplasia is a significant clinical problem for which current therapeutic approaches are largely ineffective. We continue to work with two types of intravascular devices: stents and grafts. Seeded stents have been deployed in an in vitro pulsatile flow system and cell retention and viability confirmed after exposure to physiological flow for 2 hours. We are currently testing a protocol for the implantation, in sheep femoral arteries, of stents seeded in vitro with autologous genetically marked endothelial cells. A similar autologous implantation system is being developed for seeded vascular grafts. We have constructed an in vitro flow system to test retention of seeded cells on various graft materials. Following these in vitro studies, we expect to implant seeded grafts in the sheep arterial circulation, and measure cell retention and recombinant gene expression in vivo.
