Ex vivo gene therapy with adenovirus-mediated transforming growth factor β 1 expression for endovascular treatment of aneurysm: results in a canine bilateral aneurysm model

• Published in: Journal of vascular surgery Vol. 38; no. 3; pp. 576 - 583
• Main Authors: Ribourtout, Edith, Desfaits, Anne-Cécile, Salazkin, Igor, Raymond, Jean
• Format: Journal Article
• Language: English
• Published: Mosby, Inc 2003
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/S0741-5214(03)00333-1

Endovascular treatment of cerebral aneurysm is safe and effective, but recurrence of disease is frequent compared with results with surgery. The purpose of this study was to determine the effects of recombinant transforming growth factor β 1 (rTGFβ 1) secreted by transplanted autologous vascular smooth muscle cells (VSMC) on results of endovascular treatment. VSMC from canine femoral arteries were infected with adenovirus vector encoding rTGFβ 1/green fluorescent protein (rTGFβ 1/GFP) or GFP only. rTGFβ 1 production was measured with an enzyme-linked immunosorbent assay, and autocrine and paracrine effects of rTGFβ 1 on cell functions were quantified with a proliferation assay and collagen synthesis. A bilateral carotid aneurysm model was used to compare angiographic and pathologic results after embolization with sponges seeded (n = 14) or not seeded (n = 34) with VSMC expressing TGFβ 1 or GFP (n = 7 each). Transgene retention was confirmed with Western blot analysis. In vitro, TGFβ 1 production varied from 0.9 to 180 ng/mL/d with increasing multiplicity of infection (MOI). Collagen synthesis was doubled at low (<300) MOI and increased by one and a half times at high (≥300) MOI. rTGFβ 1 was biologically active, as shown with the mink lung epithelial cell proliferation assay. VSMC grafts showed effective GFP expression up to 3 weeks after transplantation. Angiographic results were improved and neointima thickness was increased with cellular grafts, as compared with controls, but there was no significant difference between aneurysms treated with VSMC encoding rTGFβ 1/GFP or GFP vectors. Cellular grafts can promote healing of aneurysms, but overexpression of rTGFβ 1/GFP did not demonstrate added benefits in this model.