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 are currently working with two types of intravascular devices: stents and grafts. We have succeeded in seeding both of these devices with endothelial cells in which we have inserted a marker gene. We developed a pulsatile flow apparatus into which both seeded grafts and stents can be inserted. We are using this apparatus to develop protocols to optimize cell retention under physiologic flow conditions. A computerized image analysis system has also been developed, to aid in the quantitation of the coverage of grafts with seeded cells. This system is automated, easy to use, and gives quantitative, reproducible results. We expect that it will be useful in continuing studies aimed at the optimization of cell seeding and retention.
