title: Composite tissue allotransplantation in newborns: a swine model.
abstract: BACKGROUND
  Management of congenital limb aplasia or facial malformations could be improved by composite tissue allotransplantation (CTA), a technique that has never been performed in newborns. For this, however, the induction of donor-specific tolerance would be mandatory, as long-term immunosuppression is not acceptable in this non-lifesaving procedure. Induction of tolerance has been shown to be possible in a newborn CTA rat model but has never been tested in large-animal models. Our goals were to establish a model of CTA in newborn swine to see if tolerance could be obtained without immunosuppression and to assess rejection or tolerance properties via clinical and histologic examinations.
  
  
  METHODS
  We applied a CTA heterotopic knee swine model. We performed two series of surgical procedures: Series 1 was 20 autografts in 6-day-old (1-10) 2,544 kg (1,140-4,060 kg) piglets; Series 2 was 10 allografts without immunosuppression between outbred animals aged 7.8 d (6-10) and weighing 2,770 kg (2,200-3,550 kg).
  
  
  RESULTS
  In Series 1, six early deaths and two cases of vascular failure were observed. In Series 2, no spontaneous deaths were observed and all piglets presented clinical and histologic rejection.
  
  
  CONCLUSIONS
  Our findings strongly suggest that newborn immunologic status is not sufficient for the development of tolerance in large animals without immunologic intervention. Complications and animal death after transplantation correlate with age and weight. Low rates for both vascular failure and postoperative death permit the use of this model in piglets weighing over 2 kg and aged more than 6 d for research on newborn CTA.
authors.affiliation: Pediatric Orthopedic Surgery, Mother and Child Hospital, Bron, France. federico.solla@chu-lyon.fr
authors.forename: Federico
authors.initials: F
authors.lastname: Solla
authors.forename: Hua
authors.initials: H
authors.lastname: Pan
authors.forename: Dorothée
authors.initials: D
authors.lastname: Watrelot
authors.forename: Olivia
authors.initials: O
authors.lastname: Leveneur
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dubernard
authors.forename: Aram
authors.initials: A
authors.lastname: Gazarian
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology* / Q000601:surgery*; D016025:Bone Transplantation; D002356:Cartilage / Q000637:transplantation; D058752:Free Tissue Flaps / Q000601:surgery; D006614:Hindlimb / Q000601:surgery; D007108:Immune Tolerance / Q000502:physiology; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000637:transplantation; D016038:Skin Transplantation; D013552:Swine; D016378:Tissue Transplantation / Q000379:methods* / Q000502:physiology*; D023001:Transplantation Tolerance / Q000502:physiology*; D014184:Transplantation, Homologous