Single stage cell seeding of small diameter prosthetic cardiovascular grafts

Issue title: Selected Papers from the First Seminar on “Medical Engineering and Therapy”, 27–28 April 2004, Nancy, France

Article type: Research Article

Authors: Alobaid, Nasser | Salacinski, Henryk J. | Sales, Kevin M. | Hamilton, George | Seifalian, Alexander M.^{; ;}

Affiliations: Biomaterials & Tissue Engineering Centre (BTEC), Academic Division of Surgery and Interventional Sciences, University College London, London NW3 2PF, UK | Vascular Unit, Department of Surgery, Royal Free Hampstead NHS Trust Hospital, London NW3 2QG, UK

Note: [] Corresponding author: Professor Alexander M. Seifalian, Biomaterials & Tissue Engineering Centre (BTEC), Academic Division of Surgery and Interventional Sciences, University College London, Rowland Hill, Hampstead, London NW3 2PF, UK. Tel.: +44 20 7830 2901 (direct), Fax: +44 20 7472 6444; E-mail: [email protected].

Abstract: Small-diameter prosthetic cardiovascular bypass grafts have high occlusion rates. Thrombogenicity caused by the lack of endothelial cells (ECs) on the luminal surface of the grafts is one of the main reasons for its occlusion. One strategy to improve the clinical performance of cardiovascular prosthetic grafts has been to seed its luminal surface with a monolayer of the patient's own ECs. In this strategy a “two stage” seeding procedure is utilized whereby cells obtained from a vein are amplified in cell culture, then seeded onto a fibrin–arginine–glycine–aspartate (RGD) tripeptide-enriched expanded polytetrafluoroethylene (ePTFE) graft in a rotating bioreactor for one week, after which it is surgically implanted. This achieves patency rates approaching those of vein grafts. The disadvantage of two stage seeding is that it requires culture facilities, a large amount of RGD, which is expensive and is confined to elective cases because of the delay between cell cultivation, seeding, and graft implantation. A single stage seeding using freshly extracted ECs that is transplanted onto the graft at the same time frame of the bypass operation without the need for cell cultivation would be an ideal answer for the disadvantages of two stage seeding. Animal trials have been successful but human trials of single stage seeding have been disappointing. It has been hypothesized that extracted ECs are scarce, furthermore, they are washed off the graft surface once exposed to blood flow. This review examines the various techniques/technologies to improve endothelial cell extraction from various sources and retention onto the luminal surface of prosthetic cardiovascular grafts in order to develop a clinically applicable strategy for single stage seeding.

Keywords: Endothelium, seeding, vascular bypass graft, cell extraction, microvascular endothelial cells, progenitor cells, tissue engineering, polymers, cell retention

Journal: Clinical Hemorheology and Microcirculation, vol. 33, no. 3, pp. 209-226, 2005