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

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.

Fig 1.

Gross photographs of neck tissue coverage. A, The 14-day coil loops in Ad-BMP-13–treated aneurysms are embedded within thin translucent membranous tissue, which completely covers the orifice of the neck. B, The Ad-BMP-13 1-month coil loops are embedded within a moderately thick membranous tissue, which completely covers the neck. C–D, The 14-day and 1-month PAs, respectively, show that the coil loops are barely visible at the neck orifice, and no membranous tissue is visible..

Fig 2.

Photomicrographs of aneurysmal necks at 3 months. A, From the PA group, a thin neointima completely transverses the neck. The tissue appears to be concave to the aneurysm cavity (H&E, original magnification 40×). B, From the FBC group, there is a thin collagenous tissue that completely covers the neck (H&E, original magnification 60×). C, From the Ad-BMP-13 group, there is moderately thick collagenous tissue completely across the neck. (H&E, original magnification 60×). All of the tissue traversing the necks is lined with a monolayer of cells contiguous with the endothelium of the parent arteries.

Fig 3.

Photomicrographs of collagen formation. A, From the PA group, there is scant collagen within the aneurysm dome at 1 month (Masson trichrome, original magnification 100×). B, from the FBC group, there is local collagen deposition at 3 months (Masson trichrome, original magnification 100×). C–D, Both from the Ad-BMP-13 group, C shows diffuse, collagenous fibers within the dome at 1 month (Masson trichrome, original magnification 100×), and D shows a denser, more mature collagen within the dome at 6 months (Masson trichrome, original magnification 150×)..

Fig 4.

A bar chart of percent fibrosis or collagen with time and between groups. The asterisk (*) above a group indicates that it is significantly less (P < .05) than the Ad-BMP-13 group within that same time period.