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血管周细胞基质的输送部位决定了猪股动脉支架模型中狭窄的控制。

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

机构信息

Department of Research and Development, Pervasis Therapeutics, One Kendall Square, Bldg 600, 1st Fl, Cambridge, MA 02139, USA.

出版信息

J Vasc Interv Radiol. 2009 Dec;20(12):1617-24. doi: 10.1016/j.jvir.2009.08.020. Epub 2009 Oct 24.

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.

摘要

目的

在明胶基质中生长并植入受损血管外膜的内皮细胞可抑制实验模型中的狭窄。为了确定这项技术是否可以应用于微创程序,作者比较了可植入海绵中的细胞与可注射制剂的效果,并研究了支架模型中给药部位的重要性。

材料和方法

将支架植入 30 头猪的股动脉中。随后在血管周围植入海绵或注射含有同种异体内皮细胞的颗粒。对照组接受无细胞基质或不治疗。通过将细胞基质注射到血管周围组织内或附近或注射到邻近肌肉中,评估给药部位的影响。在 28 天后处死动物。在牺牲前进行血管造影和组织切片评估狭窄。

结果

用细胞基质治疗的动脉在血管造影狭窄方面降低了 55%-63%(P <.05),在组织学狭窄方面降低了 38%-43%(P <.05)与对照组相比。当细胞基质被输送到肌肉中时,内膜面积最大(6.35 平方毫米 +/- 0.95),而不是输送到或靠近血管周围组织中(分别为 4.05 平方毫米 +/- 0.56 和 4.73 平方毫米 +/- 0.53;P <.05)。

结论

血管周围内皮细胞基质可减少支架诱导损伤后的狭窄。效果不依赖于制剂,但似乎依赖于给药部位。在周围介入治疗后,将内皮细胞基质微创注入动脉外膜可能会降低再狭窄率。

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