Tissue engineering of small‐diameter vascular grafts by endothelial progenitor cells seeding heparin‐coated decellularized scaffolds

Abstract

Successful construction of a small-diameter bioartificial vascular graft remains a great challenge. This study reports on novel tissue engineering vascular grafts (TEVGs) constructed by endothelial progenitor cells and heparin-coated decellularized vessels (DV). The DVs were fabricated from canine carotid arteries with observable depletion of cellular components. After heparin coating, the scaffolds possessed excellent antithrombogeneity. Canine endothelial progenitor cells harvested from peripheral blood were expanded and seeded onto heparin-coated DVs and cocultured in a custom-made bioreactor to construct TEVGs. Thereafter, the TEVGs were implanted into the carotid arteries of cell-donor dogs. After 3 months of implantation, the luminal surfaces of TEVGs exhibited complete endothelium regeneration, however, only a few disorderly cells and thrombosis overlaid the luminal surfaces of control DVs grafts, and immunofluorescent staining showed that the seeded cells existed in the luminal sides and the medial parts of the explanted TEVGs and partially contributed to the endothelium formation. Specifically, TEVGs exhibited significantly smaller hyperplastic neointima area compared with the DVs, not only at midportion (0.64 ± 0.08 vs. 2.13 ± 0.12 mm(2) , p < 0.001), but also at anastomotic sites (proximal sites, 1.03 ± 0.09 vs. 3.02 ± 0.16 mm(2), p < 0.001; distal sites, 1.84 ± 0.15 vs. 3.35 ± 0.21 mm(2), p < 0.001). Moreover, TEVGs had a significantly higher patency rate than the DVs after 3 months of implantation (19/20 vs. 12/20, p < 0.01). Overall, this study provided a new strategy to develop small-diameter TEVGs with excellent biocompatibility and high patency rate.

45S5-Bioglass®-Based 3D-Scaffolds Seeded with Human Adipose Tissue-Derived Stem Cells Induce In Vivo Vascularization in the CAM Angiogenesis Assay

“…This approach bears the chance that the cells constantly secrete capillary recruiting mediators [27][28][29] and therefore, induce long-term vessel growth. To biofunctionalize scaffolds, high numbers of adult progenitor cells can easily be isolated, for example, from human adipose tissuederived stem cells (hASC), but they are present and responsible for tissue repair and tissue regeneration in every adult tissue.…”

Vascular Grafting Strategies in Coronary Intervention

“…In addition, immunofluorescence confirmed the presence of seeded cells lining the luminal surface of the TEVG. Significant reduction in hyperplastic neointima was also observed resulting in increased graft patency (95 versus 60% for the TEVGs and DVs, respectively) at 3 months (Zhou et al, 2012). The incorporation of the bone marrow mononuclear cells into the remodeled vascular tissue contradicts the observations of Breuer and colleagues; however, the behavior of MSCs is directly related to their perivascular environment (da Silva Meirelles et al, 2006) and may differ between humans and dogs.…”

Endothelial Outgrowth Cells: Function and Performance in Vascular Grafts

“…50 In a canine interpositional carotid implant model, EOC-seeded decellularized arteries reduced intimal thickness 3 months postimplantation throughout the length of the graft compared with grafts without EOCs. 67 Grafts wrapped with EOC-seeded scaffolds showed a significantly reduced intima-to-media ratio at 14 days post-implant, suggesting the EOCs released paracrine factors, such as NO, to inhibit intimal proliferation. 68 Together, these studies show the potential for EOCseeded vascular devices to limit intimal hyperplasia via NO release and Protein C activation.…”

“…Decellularized arteries have also been modified by covalently binding heparin to the surface before EOC seeding. 67 These grafts were cultured for 7 days under a fluid shear stress of 30 dyn/cm 2 before implantation. In a canine interpositional carotid implant model, the heparin-modified grafts seeded with EOCs demonstrated a higher 3-month patency and reduced intimal thickness throughout the length of the graft compared with unseeded heparin-modified grafts.…”