90th Annual Meeting Abstracts
Pathophysiologic Characterization of Tissue Engineered Vascular Graft Stenosis in a Murine Model
*Gustavo A Villalona, MD, *Narutoshi Hibino, MD, PhD, *Rajendra Sawh-Martinez, MS, *Edward McGillicuddy, MD, *Tamar Mirensky, MD, *Tai Yi, *Toshiharu Shinoka, MD, PhD, Christopher K Breuer, MD
Yale School of Medicine, New Haven, CT
Objective: Develop and characterize a model to understand the mechanism of TEVG stenosis and neointimal hyperplasia formation in mice.
Setting: In a previous study in Japan, 25 patients received Tissue Engineered Vascular Grafts (TEVG) in patients with single ventricle abnormalities. Follow-up angiography, however, critical luminal stenosis was identified in 20% of grafts.
Methods: TEVGs constructed from biodegradable scaffolds were implanted as interposition grafts into the inferior vena cava (IVC) of male C57/Bl6 mice (N=41). 18 scaffolds were seeded (controls) with murine total bone marrow prior implantation and 23 scaffolds were left unseeded. Serial in vivo functional graft analysis was performed after implantation in all mice using ultrasonography. All mice were sacrificed at post-implantation day 14 and the grafts analyzed using histological and immunohistochemical techniques.
Results: Seventy five percent of seeded grafts remained patent at 14 days after implantation (Figure A,C), while 89% of unseeded grafts developed critical stenoses (Figure B,D). The seeded group expressed von Willlebrand factor on the luminal aspect, consistent with graft endothelialization. Smooth muscle actin (SMA) was expressed within the stenosed area (Figure E), consistent with neointima formation (Figure F). The expression of platelet-derived growth factor-β receptor (PDGFBR) was statistically significant (Figure 2: P<0.006) for the unseeded group (Figure G) when compared to the control group (Figure H).
Conclusions: Cell seeding of TEVGs is associated with higher patency rates and early endothelialization. Platelet derived growth plays an important role in the development of TEVG failure.