Endothelial Linings in Prosthetic Vascular Grafts

Of all the animals so far studied, man is the only one known to be incapable of healing prosthetic vascular grafts with its own natural endothelium. Consequently there has been considerable effort in the 30 or so years since the first prosthetic grafts became available either to find truly nonthrombogenic artificial materials or to enhance the body’s own natural healing processes in order to provide blood-compatible devices. It has been known from the days of the earliest prosthetic grafts that the fibrin-platelet coagulum that typically lines them is an adequate surface only for grafts of 8 mm i.d. or greater. Unfortunately, the need for smaller prostheses is equal to or greater than that for the large. In the early days, emphasis in graft development was focused on different materials, such as nylon, Dacron, Teflon, tanned bovine carotid arteries, or umbilical veins as conduits. Paralleling the work with prosthetic vessels was the development of the artificial heart and the desire to provide blood-compatible linings for these devices. The idea of cell or tissue fragment seeding of prostheses in order to provide pseudointimal linings originated because of its applicability to artificial hearts (see ref. 2 for a review of this early work). Our own work in this area began with artificial hearts as well, under the auspices of the National Heart, Lung, and Blood Institute and the Artificial Heart Program. At that time the emphasis was on developing microfiber substrates upon which to grow pseudointimal linings and on finding a cell or tissue type that would provide a blood-compatible surface. In order to develop these materials and methods the prosthetic devices were fabricated into nonporous urethane tubes lined with a microfiber scaffold and of a size that could be tested by interposition in the abdominal aorta of a dog (FIG. 1). The cells were introduced into the prostheses and cultivated in vitro until a pseudointima developed. ” The progress was slow; materials were not very cell compatible, and the cells that were easily grown in vitro were thrombogenic. However, in the late 1970s several developments occurred that made cell-lined vascular grafts a practical reality. First, we and other groups of investigators finally learned how to isolate and grow adult endothelial cells. Second, we switched from the troublesome microfiber grafts to commercially available vascular prostheses (FIG. 2). Third, a new group of investigators4 discovered that scrapings from the intima of cutaneous veins, seeded into grafts in clotted blood and then immediately implanted into dogs, would produce endothelial linings in these vessels. With these developments research on endothelial cell seeding greatly increased. In the last few years endothelial cell seeding techniques have developed rapidly to the point where clinical reports of success with the method are beginning to appear’ (for a complete review, see refs. 6 and 7). In the following pages we will briefly describe the method and the current status of research in this area. This presentation is not meant to be exhaustive, but to highlight some of the more important observations as well as questions still to be answered.