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(Circulation. 2005;112:12-18.)
© 2005 American Heart Association, Inc.

Cardiovascular Surgery

In Vivo Cell Seeding With Anti-CD34 Antibodies Successfully Accelerates Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenous Expanded Polytetrafluoroethylene Grafts

Joris I. Rotmans, MD, PhD; Jan M.M. Heyligers, MD; Hence J.M. Verhagen, MD, PhD; Evelyn Velema, BSc; Machiel M. Nagtegaal, BSc; Dominique P.V. de Kleijn, PhD; Flip G. de Groot, PhD; Erik S.G. Stroes, MD, PhD; Gerard Pasterkamp, MD, PhD

From the Laboratory of Experimental Cardiology (J.I.R., E.V., D.P.V.d.K., G.P.), Department of Vascular Surgery (J.M.M.H., H.J.M.V.), and Department of Haematology (J.M.M.H., F.G.d.G.), University Medical Center, Utrecht, and Department of Vascular Medicine, Academic Medical Center, Amsterdam (J.I.R., M.M.N., E.S.G.S.), the Netherlands.

Reprint requests to Gerard Pasterkamp, MD, PhD, Laboratory of Experimental Cardiology, University Medical Center, Heidelberglaan 100, Room G02.523, Utrecht, The Netherlands. E-mail g.pasterkamp{at}hli.azu.nl

Received September 2, 2004; revision received February 17, 2005; accepted March 3, 2005.

Background— The patency of AV expanded polytetrafluoroethylene (ePTFE) grafts for hemodialysis is impaired by intimal hyperplasia (IH) at the venous outflow tract. The absence of a functional endothelial monolayer on the prosthetic grafts is an important stimulus for IH. In the present study, we evaluated the feasibility of capturing endothelial progenitor cells in vivo using anti-CD34 antibodies on ePTFE grafts to inhibit IH in porcine AV ePTFE grafts.

Methods and Results— In 11 pigs, anti-CD34–coated ePTFE grafts were implanted between the carotid artery and internal jugular vein. Bare ePTFE grafts were implanted at the contralateral side. After 3 (n=2) or 28 (n=9) days, the pigs were terminated, and the AV grafts were excised for histological analysis and SEM. At 3 and 28 days after implantation, 95% and 85% of the coated graft surface was covered by endothelial cells. In contrast, no cell coverage was observed in the bare graft at 3 days, whereas at 28 days, bare grafts were partly covered with endothelial cells (32%; P=0.04). Twenty-eight days after implantation, IH at the venous anastomosis was strongly increased in anti-CD34–coated grafts (5.96±1.9 mm²) compared with bare grafts (1.70±0.4 mm²; P=0.03). This increase in IH coincided with enhanced cellular proliferation at the venous anastomosis.

Conclusions— Autoseeding with anti-CD34 antibodies results in rapid endothelialization within 72 hours. Despite persistent endothelial graft coverage, IH at the outflow tract is increased profoundly at 4 weeks after implantation. Further modifications are required to stimulate the protective effects of trapped endothelial cells.

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CLINICAL PERSPECTIVE

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