title: Immune tolerance of epithelium-denuded-cryopreserved tracheal allograft.
abstract: OBJECTIVE
  Animal and clinical studies have demonstrated the feasibility of tracheal allograft transplantation after a revascularization period in heterotopy, thus requiring immunosuppressive therapy. Given the key role of the respiratory epithelium in the immune rejection, we investigated the consequence of both epithelium denudation and cryopreservation in immune tolerance of tracheal allograft in a novel rabbit model.
  
  
  METHODS
  Five adult female New Zealand rabbits served as donors of tracheas that were denuded of their epithelium and then cryopreserved, and 13 males were used as recipients. Following graft wrap using a lateral thoracic fascial flap, allograft segments 20 mm in length with (n = 9) or without (n = 4) insertion of an endoluminal tube were implanted under the skin of the chest wall. The animals did not receive any immunosuppressive drugs. Sacrifices were scheduled up to 91 days. Macroscopic and microscopic examinations and detection of apoptotic cells by immunohistochemical staining (Apostain) were used to study the morphology, stiffness, viability and immune rejection of allografts.
  
  
  RESULTS
  There were no postoperative complications. Grafted composite allografts displayed satisfactory tubular morphology provided that an endoluminal tube was inserted. All rabbits were found to have an effective revascularization of their allograft and a mild non-specific inflammatory infiltrate with no significant lymphocyte infiltration. Cartilage rings showed early central calcification deposit, which increased over time, ensuring graft stiffness. Apoptosis events observed into the allograft cells were suggestive of minimal chronic rejection.
  
  
  CONCLUSIONS
  Our results demonstrated that the epithelium-denuded-cryopreserved tracheal allograft implanted in heterotopy displayed satisfactory morphology, stiffness and immune tolerance despite the absence of immunosuppressive drugs. This allograft with a fascial flap transferable to the neck should be investigated in the setting of tracheal replacement in rabbits. Similar studies need to be conducted in bigger mammals before considering clinical applications.
authors.affiliation: Clinic of Cardiac and Thoracic Surgery, Lille University Teaching Hospital, CHULille, Lille, France IMPRT-IFR 114, EA 2693, Lille University Medical School, UDSL, Université Lille Nord de France, Lille, France.
authors.forename: Ilir
authors.initials: I
authors.lastname: Hysi
authors.affiliation: Clinic of Cardiac and Thoracic Surgery, Lille University Teaching Hospital, CHULille, Lille, France IMPRT-IFR 114, EA 2693, Lille University Medical School, UDSL, Université Lille Nord de France, Lille, France alain.wurtz@chru-lille.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Wurtz
authors.affiliation: IMPRT-IFR 114, EA 2693, Lille University Medical School, UDSL, Université Lille Nord de France, Lille, France Institute of Hematology-Transfusion, Lille University Teaching Hospital, CHULille, Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Zawadzki
authors.affiliation: Department of Surgical Critical Care, Lille University Teaching Hospital, CHULille, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Kipnis
authors.affiliation: European Homograft Bank, Brussels, Belgium.
authors.forename: Ramadan
authors.initials: R
authors.lastname: Jashari
authors.affiliation: IMPRT-IFR 114, EA 2693, Lille University Medical School, UDSL, Université Lille Nord de France, Lille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hubert
authors.affiliation: IMPRT-IFR 114, EA 2693, Lille University Medical School, UDSL, Université Lille Nord de France, Lille, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ung
authors.affiliation: Institute of Pathology, Lille University Teaching Hospital, CHULille, Lille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.affiliation: IMPRT-IFR 114, EA 2693, Lille University Medical School, UDSL, Université Lille Nord de France, Lille, France Institute of Hematology-Transfusion, Lille University Teaching Hospital, CHULille, Lille, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Jude
mesh_terms: D064591:Allografts / Q000098:blood supply / Q000276:immunology* / Q000637:transplantation; D000818:Animals; D017209:Apoptosis; D015925:Cryopreservation; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D007108:Immune Tolerance / Q000276:immunology*; D018919:Neovascularization, Physiologic; D011817:Rabbits; D014132:Trachea / Q000166:cytology / Q000637:transplantation*; D014184:Transplantation, Homologous / Q000379:methods*
keywords: Allograft; Animal model; Immune rejection; Trachea; Transplantation