Abstract 167: Vascular Tissue Engineering in Diabetes

Abstract

Tissue engineered blood vessels based on biological scaffolds seeded with autologous cells are currently being developed, but very little information exists regarding their fate in the complex diabetic environment. Diabetes is a major risk factor for vascular diseases as elevated levels of blood glucose and lipids interact irreversibly with long-lived proteins, such as collagen and elastin from the blood vessel wall, via oxidation and crosslinking, resulting in formation of advanced glycation end products (AGEs) and vascular stiffening. Vascular cells respond to diabetic environment by dysfunction and pathological remodeling, contributing to the onset and progression of vascular disease. These changes result in activation of inflammation, impaired healing, fibrosis, and calcification. Our hypothesis is that by reducing the level of AGEs in the cell milieu and stabilizing the matrix, vascular cells will positively contribute to the vascular wall remodeling. Therefore, acellular scaffolds prepared from renal arteries were treated with penta galoyl glucose (PGG), an antioxidant elastin-binding polyphenol, and seeded with adipose stem cells (ASCs) isolated from streptozotocin-induced diabetic rats. Constructs were analyzed for AGE formation, inflammation, and calcification after subnormal implantation as autologous cell seeded grafts, as well as by end-to-end anastomoses to the aorta. PGG-treated scaffolds showed good patency, undetectable dilatation and well-preserved elastin. ASCs seeded on scaffolds diminished macrophage infiltration, while simultaneously allowed M2 macrophage polarization. PGG-treatment and ASC seeding inhibited scaffold calcification and expression of osteogenic proteins. In conclusion, the antioxidative properties of PGG and the immunomodulatory properties of ASCs prevented vascular wall deterioration under the hostile diabetic milieu.