title: Successful orthotopic transplantation of short tracheal segments without immunosuppressive therapy.
abstract: OBJECTIVE
  Results of tracheal transplantation have been disappointing due to of ischaemia and rejection. It has been experimentally demonstrated that results of tracheal autograft/allograft transplantation were correlated with both graft length and revascularization method. Recently, we demonstrated that heterotopic epithelium-denuded-cryopreserved tracheal allograft (TA) displayed satisfactory immune tolerance. We aimed at evaluating the results of such allografts in orthotopic transplantation according to graft length and prior heterotopic or single-stage orthotopic revascularization in a rabbit model.
  
  
  METHODS
  Twenty New Zealand rabbits were used. Six females served as donors. Tracheal mucosa was mechanically peeled off and then the TAs were cryopreserved. Male recipients were divided into three groups receiving: (i) long TA segment with prior heterotopic revascularization (10-12 tracheal rings, n = 3); (ii) average TA segment with single-stage orthotopic revascularization (6-8 tracheal rings, n = 4); (iii) short TA segment with single-stage orthotopic revascularization (4-5 tracheal rings, n = 7). No immunosuppressive therapy was administered. Grafts were assessed bronchoscopically and upon death or sacrifice by macroscopic evaluation, histology and immunohistochemical staining for apoptosis.
  
  
  RESULTS
  Four animals were sacrificed from Day 33 to Day 220. The survival time of other recipients was 0-47 days (mean 19.6 ± 16.7 days). Aside from three animals that died from complications, all TA segments had satisfactory stiffness, were well vascularized, showed varying levels of neoangiogenesis and inflammatory infiltration devoid of lymphocytes, and showed evidence of only low levels of apoptosis. Varying degrees of fibroblastic proliferation originating from the lamina propria were observed in the lumen of all TAs and evolved over time into collagenized fibrosis in animals surviving over 45 days. Likewise, cartilage tracheal rings exhibited central calcification deposits, which started on Day 16 and increased over time. Epithelial regeneration was constantly observed. Intense fibroblastic proliferation led to stenosis in all animals from Groups (i) and (ii) but only one of seven animals from Group (iii).
  
  
  CONCLUSIONS
  Our results suggest that short segments of epithelium-denuded-cryopreserved TA may be reliable for tracheal transplantation in the rabbit model without problems related to graft stiffness or immune rejection. Before considering clinical applications, investigations should be conducted in larger mammals.
authors.affiliation: Cardiac and Thoracic Surgery Division, Lille University Teaching Hospital, CHU Lille, 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: Department of Surgical Critical Care, Lille University Teaching Hospital, CHU Lille, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Kipnis
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Lille University Teaching Hospital, CHU Lille, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fayoux
authors.affiliation: Institute of Pathology, Lille University Teaching Hospital, CHU Lille, 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, CHU Lille, Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Zawadzki
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: Department of Pneumology, Lille University Teaching Hospital, CHU Lille, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ramon
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, CHU Lille, Lille, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Jude
authors.affiliation: Cardiac and Thoracic Surgery Division, Lille University Teaching Hospital, CHU Lille, 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
mesh_terms: D064591:Allografts / Q000601:surgery* / Q000637:transplantation*; D000818:Animals; D017209:Apoptosis; D001999:Bronchoscopy; D005260:Female; D006084:Graft Rejection; D007165:Immunosuppression Therapy; D008297:Male; D011817:Rabbits; D014132:Trachea / Q000601:surgery* / Q000637:transplantation*; D014184:Transplantation, Homologous / Q000295:instrumentation* / Q000379:methods*
keywords: Allograft; Animal model; Immune rejection; Trachea; Transplantation