Endothelial Cell Transplantation onto Polymeric Arteriovenous Grafts Evaluated Using a Canine Model

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Abstract
Prosthetic arteriovenous grafts (AVG) placed for hemodialysis access fail in humans due to the thrombogenicity of the flow surface and development of cellular intimal hyperplasia, particularly at the venous anastomosis. The poor patency rates of prosthetic AVG result in significant morbidity and mortality in dialysis patients. Consequently, investigators have been evaluating methods to improve the patency of prosthetic grafts by examining endothelial cell transplantation as a means of creating an antithrombogenic lining on artificial polymers. A canine model was developed to study the effects of cell transplantation of autologous, fat-derived microvessel endothelial cells (MVEC) onto the luminal surface of expanded polytetrafluoroethylene (ePTFE) grafts. Microvessel endothelial cells were isolated from falciform ligament fat, with each dog receiving its own endothelial cells. Isolated cells were subsequently placed into the lumen of the graft (4 mm by 20 cm ePTFE). The graft lumen was pressurized to 5 pounds per square inch (psi) resulting in the partial denucleation of the graft, due to the flow of buffer into the interstices of the graft, and the forced deposition of cells onto the luminal surface. Animals were maintained on aspirin and persantine during the implant phase. During the implant phase, grafts were evaluated by both duplex ultrasound and magnetic resonance angiography (MRA). At explant, gross observation of the sodded grafts revealed a glistening white flow surface with no evidence of thrombosis. Morphologic and scanning electron microscopic evaluations revealed the presence of a cellular lining on the luminal flow surface that exhibited characteristics of antithrombogenic endothelial cells. Midgraft samples were evaluated by immunocytochemistry and indicated that cells on the luminal surface react positively with antibodies to von Willebrand factor. Results from this study demonstrate that the canine model provides an excellent method of studying the effects of MVEC sodding on the thrombogenicity and hyperplastic response of prosthetic arteriovenous graft.