In vivo cell seeding with anti-CD34 antibodies successfully accelerates endothelialization but stimulates intimal hyperplasia in porcine arteriovenous expanded polytetrafluoroethylene grafts

Circulation. 2005 Jul 5;112(1):12-8. doi: 10.1161/CIRCULATIONAHA.104.504407. Epub 2005 Jun 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, CD34 / immunology
  • Arteriovenous Shunt, Surgical / methods*
  • Blood Vessel Prosthesis / adverse effects*
  • Blood Vessel Prosthesis / standards
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Female
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / immunology
  • Hyperplasia / etiology*
  • Polytetrafluoroethylene / therapeutic use*
  • Renal Dialysis / adverse effects
  • Renal Dialysis / instrumentation
  • Swine
  • Tissue Engineering / methods
  • Tunica Intima / drug effects
  • Tunica Intima / pathology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD34
  • Polytetrafluoroethylene