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Comparative Study
. 2009 Dec;20(12):1617-24.
doi: 10.1016/j.jvir.2009.08.020. Epub 2009 Oct 24.

Delivery site of perivascular endothelial cell matrices determines control of stenosis in a porcine femoral stent model

Helen M Nugent  1 , Yin-Shan Ng, Desmond White, Adam Groothius, Glenn Kanner, Elazer R Edelman
Affiliations
Comparative Study

Delivery site of perivascular endothelial cell matrices determines control of stenosis in a porcine femoral stent model

Helen M Nugent et al. J Vasc Interv Radiol. 2009 Dec.

Abstract

Purpose: 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, the authors compared the effects of cells in an implantable sponge to that of 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. This was 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 < .05) and a 38%-43% reduction in histologic stenoses (P < .05) compared to controls. Intimal area was greatest when cellular matrices were delivered into the muscle (6.35 mm(2) +/- 0.95) rather than into or adjacent to the perivascular tissue (4.05 mm(2) +/- 0.56 and 4.73 mm(2) +/- 0.53, respectively; P < .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 on delivery site. Minimally invasive injections of endothelial cell matrices to the adventitia of arteries following peripheral interventions may decrease restenosis rates.

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Figures

Figure 1
Figure 1
Representative day 28 angiograms (A) and photomicrographs of Verhoeff’s elastin stained arterial cross sections (B) from the efficacy analysis. Comparison of the angiograms show significant stenosis in the stented region of control arteries (white arrows) compared to arteries treated with cell containing sponges or particles (black arrows). Histological sections show significantly greater intimal area in control sham (left panel) and Gelfoam® (middle panel) arteries compared to arteries treated with perivascular endothelial cell matrices (right panel). I = Intima, M = Media, L = Lumen.
Figure 1
Figure 1
Representative day 28 angiograms (A) and photomicrographs of Verhoeff’s elastin stained arterial cross sections (B) from the efficacy analysis. Comparison of the angiograms show significant stenosis in the stented region of control arteries (white arrows) compared to arteries treated with cell containing sponges or particles (black arrows). Histological sections show significantly greater intimal area in control sham (left panel) and Gelfoam® (middle panel) arteries compared to arteries treated with perivascular endothelial cell matrices (right panel). I = Intima, M = Media, L = Lumen.
Figure 2
Figure 2
Diagram shows particle injection sites relative to the femoral artery. Injections of particles into the perivascular tissue (a), adjacent to the perivascular tissue (b) and into the muscle capsule (c).
Figure 3
Figure 3
Representative day 28 angiographic measurements (A) and photomicrographs of Verhoeff elastin stained arterial cross sections (B) from the injection site analysis. Bar graph shows the average percentage of stenosis as a function of injection site. *P<0.05 compared to the other two groups. Greater intimal formation was observed for arteries treated with cellular matrices injected into the muscle capsule (B, right panel) compared to arteries treated with cellular matrices injected into or adjacent to the perivascular tissue (B, left and middle panels, respectively). I = Intima, M = Media, L = Lumen.
Figure 3
Figure 3
Representative day 28 angiographic measurements (A) and photomicrographs of Verhoeff elastin stained arterial cross sections (B) from the injection site analysis. Bar graph shows the average percentage of stenosis as a function of injection site. *P<0.05 compared to the other two groups. Greater intimal formation was observed for arteries treated with cellular matrices injected into the muscle capsule (B, right panel) compared to arteries treated with cellular matrices injected into or adjacent to the perivascular tissue (B, left and middle panels, respectively). I = Intima, M = Media, L = Lumen.
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References

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