SP497CHRONIC KIDNEY DISEASE DOES NOT IMPACT THE MORPHOLOGY AND CELLULAR COMPOSITION OF IN VIVO TISSUE ENGINEERED BLOOD VESSELS IN RATS

Abstract

Introduction and Aims: Tissue engineered blood vessels (TEBVs) could offer a suitable alternative for arteriovenous conduits, circumventing the limitations of synthetic grafts and avoiding the need for maturation of fistulas. Recently, we developed a novel method to generate TEBVs by utilizing the foreign body response directed to a subcutaneously implanted polymeric rod, which culminates in the formation of a fibrocellular tissue capsule (TC). Upon extrusion of the polymer rod, the remaining TC is grafted into the vasculature whereupon it differentiates towards a blood vessel. In the present study, the impact of chronic kidney disease (CKD) on TC formation was evaluated in a rat model. Methods: Polymeric rods were subcutaneously implanted in CKD rats (5/6 nephrectomy model; n=7) and left in place for 1, 3 or 6 weeks. TCs were harvested and their cellular composition as well as gene expression profile was analysed and compared with healthy rats (n=7). Results: In both groups, TCs were mainly composed of circumferentially aligned collagen layer and alphaSMA(+), vimentin(+) and desmin(-) myofibroblasts. Collagen organisation gradually changed in time from a disorganized structure at 1 week towards circumferentially aligned fibres at 6 weeks. Its density was significantly higher 6 weeks after implantation compared to the 3 weeks' time point (Fig.1A). Initial cellular response upon rod implantation is characterized by a high infiltration of pro-inflammatory CD68 (+)/ MCP1(+) macrophages whereas after 6 weeks the response changed towards more tissue-repair with a high number of anti-inflammatory CD68(+)/ CD163(+) macrophages (Fig.1B). Interestingly, the most inner layer of the TC at 6 weeks was composed of alphaSMA(+)/ CD68(+) cells, suggesting a crucial role of inflammatory cells as precursors of myofibroblasts in matured TC (Fig.1C). No differences in TC thickness, collagen content, inflammatory cells density and myofibroblast content were observed between groups. Conclusions: CKD has no impact on TC morphology and composition, making our in vivo approach of autologous vascular tissue engineering a relevant strategy for future clinical use in hemodialysis patients. (Figure Presented).