Delivery Site of Perivascular Endothelial Cell Matrices Determines Control of Stenosis in a Porcine Femoral Stent Model

Abstract

PURPOSE: High restenosis rates are a major limitation of peripheral interventions. Endothelial cells, grown within gelatin matrices and implanted onto the adventitia of injured vessels, inhibit stenosis in experimental models. To determine if this technology could be adapted for minimally invasive procedures, we compared the effects of cells in an implantable sponge to an injectable formulation and investigated the importance of delivery site in a stent model. MATERIALS AND METHODS: Stents were implanted in the femoral arteries of 30 pigs followed by perivascular implantation of sponges or injection of particles containing allogeneic endothelial cells. Controls received acellular matrices or nothing. The effects of delivery site were assessed by injecting cellular matrices into or adjacent to the perivascular tissue, or into the neighboring muscle. Animals were sacrificed after 28 days. Pre-sacrifice angiograms and tissue sections were evaluated for stenosis. RESULTS: Arteries treated with cellular matrices had a 55 – 63% decrease in angiographic stenosis (P<0.05) and a 38 – 43% reduction (P<0.05) in histologic stenoses compared to controls. Intimal area was greatest when cellular matrices were delivered into the muscle (6.35 ± 0.95 mm2) compared to into or adjacent to the perivascular tissue (4.05 ± 0.56 mm2 and 4.73 ± 0.53 mm2, respectively, P < 0.05). CONCLUSIONS: Perivascular endothelial-cell matrices reduced stenosis after stent-induced injury. The effects were not dependent on the formulation but appeared to be dependent upon delivery site. Minimally invasive injections of endothelial-cell matrices to the adventitia of arteries following peripheral interventions may decrease restenosis rates.