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使用转染了含骨形态发生蛋白-13基因的复制缺陷型腺病毒的成纤维细胞对实验性动脉瘤进行血管内治疗。

Endovascular treatment of experimental aneurysms with use of fibroblast transfected with replication-deficient adenovirus containing bone morphogenetic protein-13 gene.

作者信息

Dai D, Ding Y H, Danielson M A, Kadirvel R, Helm G A, Lewis D A, Cloft H J, Kallmes D F

机构信息

Neuroradiology Research Laboratory, Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA.

出版信息

AJNR Am J Neuroradiol. 2008 Apr;29(4):739-44. doi: 10.3174/ajnr.A0892. Epub 2008 Jan 9.

Abstract

BACKGROUND AND PURPOSE

Modified coils have failed to improve long-term recanalization of aneurysms. This study examined whether ex vivo transduction of replication-deficient adenovirus containing the bone morphogenetic protein-13 gene (Ad-BMP-13) in fibroblast allografts would improve angiographic results via increased collagen synthesis, compared with fibroblast-coated platinum coils (FBC) and bare platinum coils (PA).

MATERIALS AND METHODS

Aneurysms were embolized with Ad-BMP-13-coated coils (n = 20). Rabbits were sacrificed at 14 days and at 1, 3, and 6 months after implantation. Digital subtraction angiography (DSA) evaluated stability after embolization. Histologic specimens were examined with a qualitative grading system. Masson trichrome evaluated collagen deposition. Findings were compared with previously reported controls for PA and FBC in the same model and time points.

RESULTS

The grading system showed a greater total score (P = .0002) in Ad-BMP-13 (6.8 +/- 1.6) and FBC (6.3 +/- 2.4) compared with PA (4.7 +/- 2.4). A group main effects test showed that aneurysm neck tissue coverage in Ad-BMP-13 (2.5 +/- 1.1) was higher (P = .0007) than both FBC (1.6 +/- 1.4) and PA (0.9 +/- 1.1). Ad-BMP-13 had more (P < .0001) collagen deposition than the FBC and PA. One- and 3-month Ad-BMP-13 collagen depositions increased (P < .05) over the FBC and PA. Finally, Ad-BMP-13 showed radiographic stability in 15 (75%) cases, coil compaction in 4 (20%) cases, and progressive occlusion in 1 (5%) case. There were no differences in angiographic results (P = .6522).

CONCLUSION

The Ad-BMP-13-coated coils can improve neck coverage and dome fibrosis in the rabbit model, even in the absence of observed differences in angiographic outcome.

摘要

背景与目的

改良型线圈未能改善动脉瘤的长期再通情况。本研究检测了与成纤维细胞包被的铂线圈(FBC)和裸铂线圈(PA)相比,在同种异体成纤维细胞移植物中对含骨形态发生蛋白-13基因(Ad-BMP-13)的复制缺陷型腺病毒进行体外转导是否会通过增加胶原蛋白合成来改善血管造影结果。

材料与方法

用Ad-BMP-13包被的线圈栓塞动脉瘤(n = 20)。在植入后14天以及1、3和6个月处死兔子。数字减影血管造影(DSA)评估栓塞后的稳定性。组织学标本采用定性分级系统进行检查。Masson三色染色法评估胶原蛋白沉积情况。将结果与同一模型和时间点之前报道的PA和FBC对照组进行比较。

结果

分级系统显示,与PA(4.7±2.4)相比,Ad-BMP-13组(6.8±1.6)和FBC组(6.3±2.4)的总分更高(P = 0.0002)。一项组主效应检验显示,Ad-BMP-13组(2.5±1.1)的动脉瘤颈部组织覆盖率高于FBC组(1.6±1.4)和PA组(0.9±1.1)(P = 0.0007)。Ad-BMP-13组的胶原蛋白沉积比FBC组和PA组更多(P < 0.0001)。Ad-BMP-13组在1个月和3个月时的胶原蛋白沉积比FBC组和PA组增加(P < 0.05)。最后,Ad-BMP-13组在15例(75%)病例中显示出影像学稳定性,4例(20%)病例出现线圈压实,1例(5%)病例出现渐进性闭塞。血管造影结果无差异(P = 0.6522)。

结论

在兔模型中,Ad-BMP-13包被的线圈可改善颈部覆盖率和瘤顶纤维化,即使在血管造影结果未观察到差异的情况下也是如此。

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