TRANSMURAL ENDOTHELIALIZATION OF VASCULAR PROSTHESES IS REGULATED IN-VITRO BY FIBROBLAST GROWTH-FACTOR-2 AND HEPARAN-LIKE MOLECULE

Endothelialization of vascular prostheses may result from transmural m igration of endothelial cells. Angiogenesis is controlled by growth fa ctors like Fibroblast Growth Factor 2 (FGF2) and regulators like hepar an-like molecules. To that end, we used heparan-like molecules named R GTA for ReGeneraTing Agent. The RGTA11 used was a chemically derived d extran obtained by successive substitutions with carboxymethyl, benzyl amide, and benzylamide sulfonate groups on glucose residues. This agen t was further selected for its ability to bind, stabilize and prefect FGF2. We defined firstly the angiogenic capability of FGF2 in combinat ion with RGTA11 on bovine aortic endothelial cells (BAEC) cultured on collagen I gels. Secondly the role of FGF2 and RGTA11 in transmural en dothelialization was assessed in a three-dimensional in vitro model us ing a polyethylene terephtalate prosthesis included in collagen gel. B AEC seeded on the external face can migrate to the luminal face of the prosthesis. Microscopic and histological evaluations were performed a t 4 and 7 days. Results showed that the addition of RGTA11 alone did n ot promote angiogenesis while FGF2 alone did. However, RGTA11 combined with FGF2 produced a significant acceleration in angiogenesis compare d to FGF2 alone. This combination magnifies and enhances the angiogeni c processes leading to endothelialization of luminal face through tran smural cellular migration. Our data demonstrates that in vitro transmu ral endothelialization of porous vascular prostheses by BAEC cultured on collagen I gels is upregulated by RGTA11 combined with FGF2.