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. During the past year we continued our work on seeding of prosthetic vascular grafts. In previous work, retention of seeded cells on prosthetic graft materials was studied in an in vitro flow system. During this year we extended these studies in vivo by implanting seeded grafts in sheep carotid and femoral arteries. Retention of the seeded cells was measured 2 hours after implantation, with approximately 10% of the cells remaining adherent. These cells were viable as judged by their ability to express recombinant human tissue plasminogen activator driven by an inserted transgene. No viable cells were detected at 1 week. Work is now in progress to optimize cell adherence and proliferation by specific techniques that include manipulation of extracellular matrix composition.
