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. Following successful in vitro cell retention studies, we implanted seeded stents into the femoral arteries of living sheep. While there appears to be no detrimental effect of seeding on stent patency and endothelialization, thus far we have had difficulty establishing that the seeded cells survive and proliferate in vivo. In one case we recovered the implanted cells after 2 hours in vivo and demonstrated their continued viability. However in several other cases we were unable to recover viable seeded cells either immediately after deployment or at the 2 hour time point. Results obtained at longer time points, using autologous implanted cells, are pending. A similar autologous implantation system is being developed for seeded vascular grafts. Three prosthetic graft materials are being compared for their ability both to be seeded with transduced endothelial cells and to retain these cells under flow conditions in vitro. Woven polyurethane and knitted Dacron both appear superior to polytetrafluoroethylene in their ability to allow the attachment and retention of large numbers of viable cells. The results of these in vitro studies will guide our approach to in vivo studies involving the implantation of seeded grafts.
