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Autologous Endothelial Progenitor Cell-Seeding Technology and Biocompatibility Testing For Cardiovascular Devices in Large Animal Model
Published on: September 9, 2011
Single stage cell seeding of small diameter prosthetic cardiovascular grafts
Nasser Alobaid1, Henryk J Salacinski, Kevin M Sales
1Biomaterials & Tissue Engineering Centre (BTEC), Academic Division of Surgery and Interventional Sciences, University College London, London NW3 2PF, UK.
Insights
Improving cardiovascular grafts requires effective endothelial cell (EC) seeding. This review explores methods to enhance EC extraction and retention for single-stage seeding, aiming to overcome limitations of current two-stage procedures.
Area of Science:
- Biomaterials Science
- Cardiovascular Engineering
- Cell Biology
Background:
- Small-diameter prosthetic cardiovascular grafts exhibit high occlusion rates, primarily due to graft thrombogenicity.
- Endothelial cell (EC) coverage on the graft's luminal surface is crucial for preventing thrombogenicity and improving graft patency.
- Current two-stage EC seeding methods involve cell culture and enrichment with fibrin-arginine-glycine-aspartate (RGD) tripeptide on expanded polytetrafluoroethylene (ePTFE) grafts, which are costly and time-consuming.
Purpose of the Study:
- To review techniques for improving endothelial cell (EC) extraction from various sources.
- To examine strategies for enhancing EC retention on prosthetic cardiovascular graft surfaces.
- To develop a clinically applicable single-stage EC seeding strategy for cardiovascular grafts.
Main Methods:
- Review of existing literature on EC extraction techniques.
- Analysis of methods for improving EC adhesion and retention on ePTFE grafts.
- Evaluation of single-stage versus two-stage EC seeding approaches.
Main Results:
- Single-stage EC seeding has shown promise in animal trials but faces challenges in human applications.
- Limited EC availability and washout from the graft surface upon blood flow exposure are key issues in single-stage seeding.
- Various techniques are being investigated to optimize EC extraction and secure their retention on graft surfaces.
Conclusions:
- Overcoming the limitations of two-stage EC seeding requires advancements in single-stage methods.
- Improving EC extraction efficiency and retention mechanisms is critical for successful clinical translation of single-stage seeding.
- Developing effective single-stage EC seeding strategies could significantly enhance the performance of prosthetic cardiovascular grafts.
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.

