Functional Small-Diameter Human Tissue–Engineered Arterial Grafts in an Immunodeficient Mouse Model

Abstract

HYPOTHESIS: The immunodeficient (severe combined immunodeficiency beige [SCID/bg]) mouse model provides a useful model for investigating vascular neotissue formation in human tissue-engineered arterial conduits (TEAC). DESIGN: Human aortic smooth muscle cells and endothelial cells were statically seeded on porous biodegradable polymeric scaffolds for vascular tissue engineering. These 2-cell tissue-engineered vascular conduits were implanted into immunodeficient female mice as aortic interposition grafts. Grafts were evaluated over a 30-week course to investigate their patency and structure. SETTING: In vivo animal study. PATIENTS: Thirteen female C.B-17 SCID/bg mice. INTERVENTION: The TEACs implanted as infrarenal abdominal aortic interposition grafts. MAIN OUTCOME MEASURES: Selective microcomputed tomography with intra-arterial contrast revealed graft patency and structure. Histological and immunohistochemical evaluations revealed cellularity and extracellular matrix composition. Species-specific immunohistochemical evaluation determined the source of cells within TEACs. RESULTS: All TEACs were patent without evidence of thrombosis or rupture over the 30-week course. Histological and immunohistochemical evaluation revealed a von Willebrand factor-positive luminal monolayer surrounded by concentric collagen-rich layers of alpha-smooth muscle actin-positive cells. CONCLUSIONS: The SCID/bg mouse is a useful model for investigating vascular neotissue formation in human TEACs. We see evidence that these grafts remain patent while developing into vascular neotissue histologically similar to native aorta. This chimeric animal model also enables determination of seeded cell retention, providing insight into cellular mechanisms underlying neotissue formation.