title: Life-supporting human complement regulator decay accelerating factor transgenic pig liver xenograft maintains the metabolic function and coagulation in the nonhuman primate for up to 8 days.
abstract: BACKGROUND
  It is not known whether the pig liver is capable of functioning efficiently when transplanted into a primate, neither is there experience in transplanting a liver from a transgenic pigs expressing the human complement regulator human complement regulator decay accelerating factor (h-DAF) into a baboon. The objective of this study was to determine whether the porcine liver would support the metabolic functions of non-human primates and to establish the effect of hDAF expression in the prevention of hyperacute rejection of porcine livers transplanted into primates.
  
  
  METHODS
  Five orthotopic liver xenotransplants from pig to baboon were carried out: three from unmodified pigs and two using livers from h-DAF transgenic pigs.
  
  
  RESULTS
  The three control animals transplanted with livers from unmodified pigs survived for less than 12 hr. Baboons transplanted with livers from h-DAF transgenic pigs survived for 4 and 8 days. Hyperacute rejection was not detected in the baboons transplanted with hDAF transgenic pig livers; however, it was demonstrated in the three transplants from unmodified pigs. Baboons transplanted with livers from h-DAF transgenic pigs were extubated at postoperative day 1 and were awake and able to eat and drink. In the recipients of hDAF transgenic pig livers the clotting parameters reached nearly normal levels at day 2 after transplantation and remained normal up to the end of the experiments. In these hDAF liver recipients, porcine fibrinogen was first detected in the baboon plasma 2 hr postreperfusion, and was present up to the end of the experiments. One animal was euthanized at day 8 after development of sepsis and coagulopathy, the other animal arrested at day 4, after an episode of vomiting and aspiration. The postmortem examination of the hDAF transgenic liver xenografts did not demonstrate rejection.
  
  
  CONCLUSIONS
  The livers from h-DAF transgenic pigs did not undergo hyperacute rejection after orthotopic xenotransplantation in baboons. When HAR is abrogated, the porcine liver maintains sufficient coagulation and protein levels in the baboon up to 8 days after OLT.
authors.affiliation: Department of Surgery, University Hospital Virgen Arrixaca, Murcia, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Ramirez
authors.forename: R
authors.initials: R
authors.lastname: Chavez
authors.forename: M
authors.initials: M
authors.lastname: Majado
authors.forename: V
authors.initials: V
authors.lastname: Munitiz
authors.forename: A
authors.initials: A
authors.lastname: Muñoz
authors.forename: Q
authors.initials: Q
authors.lastname: Hernandez
authors.forename: C G
authors.initials: CG
authors.lastname: Palenciano
authors.forename: G
authors.initials: G
authors.lastname: Pino-Chavez
authors.forename: M
authors.initials: M
authors.lastname: Loba
authors.forename: A
authors.initials: A
authors.lastname: Minguela
authors.forename: J
authors.initials: J
authors.lastname: Yelamos
authors.forename: M R
authors.initials: MR
authors.lastname: Gago
authors.forename: A S
authors.initials: AS
authors.lastname: Vizcaino
authors.forename: H
authors.initials: H
authors.lastname: Asensi
authors.forename: M G
authors.initials: MG
authors.lastname: Cayuela
authors.forename: B
authors.initials: B
authors.lastname: Segura
authors.forename: F
authors.initials: F
authors.lastname: Marin
authors.forename: A
authors.initials: A
authors.lastname: Rubio
authors.forename: T
authors.initials: T
authors.lastname: Fuente
authors.forename: R
authors.initials: R
authors.lastname: Robles
authors.forename: F S
authors.initials: FS
authors.lastname: Bueno
authors.forename: T
authors.initials: T
authors.lastname: Sansano
authors.forename: F
authors.initials: F
authors.lastname: Acosta
authors.forename: J M
authors.initials: JM
authors.lastname: Rodriguez
authors.forename: F
authors.initials: F
authors.lastname: Navarro
authors.forename: J
authors.initials: J
authors.lastname: Cabezuelo
authors.forename: E
authors.initials: E
authors.lastname: Cozzi
authors.forename: D J
authors.initials: DJ
authors.lastname: White
authors.forename: R Y
authors.initials: RY
authors.lastname: Calne
authors.forename: P
authors.initials: P
authors.lastname: Parrilla
mesh_terms: D000208:Acute Disease; D000818:Animals; D030801:Animals, Genetically Modified; D001779:Blood Coagulation Factors / Q000032:analysis; D018958:CD55 Antigens / Q000494:pharmacology*; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015941:Complement Hemolytic Activity Assay; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D010215:Papio; D015996:Survival Rate; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000502:physiology*
chemical_list: D001779:Blood Coagulation Factors; D018958:CD55 Antigens; D003176:Complement C3; D003181:Complement C4