Endothelialization of Bypass Grafts Using Autologous Stem Cells

University of Minnesota Ph.D. dissertation.September 2018. Major: Biomedical Engineering. Advisors: Bob Tranquillo, Brenda Ogle. 1 computer file (PDF); ix, 82 pages.Coronary artery disease is the most common type of cardiovascular disease and the leading cause of death in the United States. Coronary artery bypass grafting (CABG) is the standard of care but may be limited by the availability of suitable autologous grafts. Despite synthetic substitutes showing success in large-diameter bypass grafts, they are not suitable for replacing small-diameter vessels. Tissue-engineered vascular grafts (TEVG) can address limited availability of autologous vessel grafts. Endothelialization of luminal grafts can be done through pre-seeding with non-thrombogenic cells. Adipose-derived mesenchymal stem cells (ASCs) are good source of autologous stem cells for vascular differentiation, especially endothelial cells (ECs). In this work, we seeded ASCs onto fibroblast-remodeled fibrin tissues to create a hemocompatible TEVGs. We investigated the effects of shear stress, cyclic stretching, and simultaneous cyclic stretching and shear stress (resulted from pulsatile fluid flow) in differentiating ASCs towards ECs. Conditioned-ASCs aligned with the direction of flow but perpendicular to the direction of cyclic stretching. Although no detection of endothelial markers in conditioned-ASCs was observed, we found a reduction in platelet binding and an increased in nitric oxide production after exposure to biomechanical forces, indicating a potential utility of ASCs as non-thrombogenic luminal surface