Research Project
3502477
The major factor limiting more widespread utilization of allogeneic veins in arterial bypass procedures is the recipients' immune response. The intimal endothelial cells appear to be the focus of this immune response, which results in loss of the intimal lining of the vessel lumen during the first two weeks after transplantation and the longer-term risk of occlusion. This proposal will examine the hypothesis that ultraviolet B (UVB) irradiation may reduce the immunostimulatory capabilities of allogeneic canine saphenous veins, while preserving cell viability. Initial in vitro experiments will determine whether UVB irradiation of endothelial cells can induce immunological tolerance in mixed cultures of irradiated endothelial cells and non-irradiated allogeneic peripheral blood mononuclear cells. In situ experiments will then be performed, using UVB doses defined in vitro, to select a dose with maximal in vitro effect and minimal in situ losses of cell viability. An in vivo transplantation study will then be performed to determine the effects of this selected UVB irradiation dose on endothelial cell survival and allograft patency. If the results of this feasibility study are positive, human saphenous veins will be studied in the next, Phase II, grant application. Reduction of the immunological consequences of venous allografting would justify the use of allograft veins in a broad range of clinical applications.
