Intravascular local gene transfer mediated by protein-coated metallic stent

Objective To assess the feasibility, efficiency and selectivity of adenovir us-mediated gene transfer to local arterial wall by protein-coated metallic stent. Methods A replication-defective recombinant adenovirus carrying the Lac Z r eporter gene for nuclearspecific beta -galactosidase (Ad-beta gal) was used in this study. The coating for metallic stent was made by immersing it in a gelatin solution containing crosslinker. The coated stents were mounted o n a 4.0 or 3. 0 mm percutaneous transluminal coronary angioplasty ( PTCA) b alloon and submersed into a high-titer Ad-beta gal viral stock (2 x 10(10) pfu/ml) for 3 min, and then implanted into the carotid arteries in 4 mini-s wines and into the left anterior descending branch of the coronary artery i n 2 mini-swines via 8F large lumen guiding catheters. The animals were sacr ificed 7 (n = 4), 14 ( n = 1) and 21 ( n = 1) days after implantation, resp ectively. The beta -galactosidase expression was assessed by X-gal staining . Results The results showed that the expression of transgene was detected in all animal. In 1 of carotid artery with an intact intima, the beta -gal ex pression was limited to endothelial cells. In vessels with denuded endothel ium, gene expression was found in the sub-intima, media and adventitia. The transfection efficiency of medial smooth muscle cells was 38.6%. In 2 anim als sacrificed 7 days after transfection, a microscopic examination of X-ga l-stained samples did not show evidence of transfection in remote organs an d arterial segments adjacent to the treated arterial site. Conclusions Adenovirus-mediated arterial gene transfer to endothelial, smoo th muscle cells and adventitia by protein-coated metallic stent is feasible . The transfection efficiency is higher. The coated stent may act as a good carrier of adenovirus-mediated gene transfer and have a potential to preve nt restenosis following PTCA.