title: Contaminants from the transplant contribute to intimal hyperplasia associated with microvascular endothelial cell seeding.
abstract: OBJECTIVE
  seeding prosthetic grafts with fat-derived microvascular endothelial cells (MVEC) results not only in a non-thrombogenic EC layer, but also in intimal hyperplasia. Here we investigated incidence, composition, progression, and cause of this intimal hyperplasia.
  
  
  METHODS
  EPTFE grafts with MVEC were implanted as carotid interpositions in six dogs with 1 month, and in three dogs with 4, 8 and 12 months follow-up. Grafts seeded without cells, implanted in the contralateral carotid, served as a control. In another three dogs labelled cells were seeded to investigate the contribution of the seeded cells (2-3 weeks).
  
  
  METHODS
  MVEC were isolated from the falciform ligament. Cells were pressure seeded on ePTFE grafts. Labelling was performed using retroviral gene transduction. The grafts were analysed with immunohistochemical techniques.
  
  
  RESULTS
  after 1 month, all patent non-seeded grafts (5/6) showed fibrin and platelet deposition, and all patent seeded grafts (5/6) were covered with a confluent endothelial monolayer on top of a multilayer of myofibroblasts, elastin and collagen. After long term follow-up, all non-seeded grafts were occluded, all patent seeded grafts (4 and 12 months) were covered with an EC-layer with intimal hyperplasia underneath. The thickness of the intima did not progress after 1 month. Transduced cells were found in the endothelial monolayer, hyperplastic intima and luminal part of the prosthesis.
  
  
  CONCLUSIONS
  MVEC seeding in dogs results in intimal hyperplasia in all patent grafts, which contains myofibroblasts. Contaminants from the transplant contribute to this intimal hyperplasia.
authors.affiliation: Department of Vascular and Transplantation Surgery, University Medical Center, Utrecht, The Netherlands.
authors.forename: C H P
authors.initials: CH
authors.lastname: Arts
authors.forename: P Ph A
authors.initials: PP
authors.lastname: Hedeman Joosten
authors.forename: J D
authors.initials: JD
authors.lastname: Blankensteijn
authors.forename: F J T
authors.initials: FJ
authors.lastname: Staal
authors.forename: P Y Y
authors.initials: PY
authors.lastname: Ng
authors.forename: G J
authors.initials: GJ
authors.lastname: Heijnen-Snyder
authors.forename: J J
authors.initials: JJ
authors.lastname: Sixma
authors.forename: H J M
authors.initials: HJ
authors.lastname: Verhagen
authors.forename: P G
authors.initials: PG
authors.lastname: de Groot
authors.forename: B C
authors.initials: BC
authors.lastname: Eikelboom
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation; D002339:Carotid Arteries / Q000601:surgery; D002478:Cells, Cultured; D004285:Dogs; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology* / Q000473:pathology; D018014:Gene Transfer Techniques; D006083:Graft Occlusion, Vascular / Q000473:pathology* / Q000503:physiopathology; D006965:Hyperplasia; D007150:Immunohistochemistry; D011138:Polytetrafluoroethylene; D023822:Tissue Engineering; D017539:Tunica Intima / Q000473:pathology*; D014654:Vascular Patency
chemical_list: D011138:Polytetrafluoroethylene