title: Hepatic function after genetically engineered pig liver transplantation in baboons.
abstract: BACKGROUND
  If "bridging" to allo-transplantation (Tx) is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured.
  
  
  METHODS
  We have studied hepatic function in baboons after Tx of livers from alpha1,3-galactosyltransferase gene-knockout (GTKO, n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46, n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In four baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs.
  
  
  RESULTS
  Recipient baboons died or were euthanized after 4 to 7 days after internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, and plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed.
  
  
  CONCLUSIONS
  After the Tx of genetically engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near normal; (2) there was evidence for production of pig proteins, including coagulation factors; and (3) these appeared to function adequately in baboons although interspecies compatibility of such proteins remains to be confirmed.
authors.affiliation: Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Burcin
authors.initials: B
authors.lastname: Ekser
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Echeverri
authors.forename: Andrea Cortese
authors.initials: AC
authors.lastname: Hassett
authors.forename: Mark H
authors.initials: MH
authors.lastname: Yazer
authors.forename: Cassandra
authors.initials: C
authors.lastname: Long
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.forename: Chih Che
authors.initials: CC
authors.lastname: Lin
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van der Windt
authors.forename: Eefje M
authors.initials: EM
authors.lastname: Dons
authors.forename: Carol
authors.initials: C
authors.lastname: Phelps
authors.forename: David
authors.initials: D
authors.lastname: Ayares
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
authors.forename: Bruno
authors.initials: B
authors.lastname: Gridelli
mesh_terms: D000818:Animals; D001779:Blood Coagulation Factors / Q000096:biosynthesis / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005818:Genetic Engineering / Q000379:methods*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000379:methods / Q000502:physiology*; D008297:Male; D010215:Papio; D011516:Prothrombin / Q000378:metabolism; D013045:Species Specificity; D013552:Swine; D016559:Tacrolimus / Q000627:therapeutic use; D014183:Transplantation, Heterologous / Q000276:immunology / Q000502:physiology*; D014184:Transplantation, Homologous / Q000502:physiology
chemical_list: D001779:Blood Coagulation Factors; D007166:Immunosuppressive Agents; D011516:Prothrombin; D016559:Tacrolimus