These results demonstrate that the adventitial application of endothelial implants significantly reduced MMP-2 expression within the venous wall, and increased venous lumen diameter and positive remodeling in a porcine arteriovenous graft model. Adventitial endothelial implants may be useful in decreasing luminal narrowing in a clinical setting.
Cases of active tuberculosis are increasing among pregnant women in epidemic communities and are associated with HIV infection. Early tuberculin skin test screening with appropriate preventive therapy should reduce morbidity due to tuberculosis in HIV-infected women of reproductive age. Identification of pregnant women with tuberculosis requires a high index of suspicion.
Objective
High restenosis rates are a limitation of peripheral vascular interventions. Previous studies have shown that surgical implantation of a tissue-engineered endothelium onto the adventitia surface of injured vessels regulates vascular repair. In the present study, we developed a particulate formulation of tissue-engineered endothelium and a method to deliver the formulation perivascular to injured blood vessels using a percutaneous, minimally invasive technique.
Methods
Stainless steel stents were implanted in 18 balloon-injured femoral arteries of nine domestic swine, followed by ultrasound-guided percutaneous perivascular injection of gelatin particles containing cultured allogeneic porcine aortic endothelial cells (PAE). Controls received injections of empty particles (matrix) or no perivascular injection (sham) after stent deployment. Animals were sacrificed after 90 days.
Results
Angiographic analysis revealed a significantly greater lumen diameter in the stented segments of arteries treated with PAE/matrix (4.72 ± 0.12 mm) compared with matrix (4.01 ± 0.20 mm) or sham (4.03 ± 0.16 mm) controls (P< .05). Similarly, histologic analysis revealed that PAE/matrix-treated arteries had the greatest lumen area(20.4 ± 0.7 mm2; P< .05) compared with controls (16.1 ± 0.9 mm2 and 17.1 ±1.0 mm2 for sham and matrix controls, respectively) and the smallest intimal area (3.3 ± 0.4 mm2; P < .05) compared with controls (6.2 ±0.5 mm2 and 4.4 ±0.5 mm2 for sham and matrix controls, respectively). Overall, PAE-treated arteries had a 33% to 50% decrease in percent occlusion (P < .05) compared with controls. Histopathological analysis revealed fewer leukocytes present in the intima in the PAE/matrix group compared with control groups, suggesting that the biological effects were in part due to inhibition of the inflammatory phase of the vascular response to injury.
Conclusions
Minimally invasive, perivascular delivery of PAE/matrix to stented arteries was performed safely using ultrasound-guided percutaneous injections and significantly decreased stenosis. Application at the time of or subsequent to peripheral interventions may decrease clinical restenosis rates.
Vascular access dysfunction is a major problem in hemodialysis patients. Arteriovenous (AV) grafts have a patency rate of only 50% at 1 year. Vein maturation is an important factor in the success of an AV graft, the vein must remodel to accommodate arterial blood flow and pressure. We examined the role of perivascular endothelial implants in venous remodeling and stenosis. The data presented here provides insight into the mechanism of the implants and AV graft failure. End‐to‐side carotid artery‐jugular vein AV grafts were created in swine and the anastomoses wrapped with Gelfoam® matrices containing porcine endothelial cells (PAE, n = 10) or control matrices without cells (n = 10). The biological response was investigated at 3 days and 1‐month post‐operatively. PAE implants significantly increased venous lumen gain. The treated veins increased in diameter from 1.04 ± 0.09 at day 0 to 2.9 ± 0.56 at 1‐month, P<0.05, while control veins remained unchanged from 1.28 ± 0.13 at day 0 to 1.29 ± 0.35 at 1‐month (Fig. ). The implants also reduced the percent stenosis by 81%, P<0.05. These data correlated with a significant reduction in MMP‐2 expression (Fig. ), adventitial fibrosis and neovascularization in treated veins compared to control, P<0.05. This study suggests that PAE implants significantly increased venous lumen diameter and reduced stenosis at 1‐month in porcine AV grafts.
Funding provided by Pervasis Therapeutics.
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