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.
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: Yau-Lin Tseng; Kenji Kuwaki; Frank J M F Dor; Akira Shimizu; Stuart Houser; Yosuke Hisashi; Kazuhiko Yamada; Simon C Robson; Michel Awwad; Henk-Jan Schuurman; David H Sachs; David K C Cooper Journal: Transplantation Date: 2005-11-27 Impact factor: 4.939
Authors: M Adham; J M Sab; C Ducerf; D Tassaux; C Vianey-Saban; M Chevallier; E de la Roche; Q V Le; T Bizollon; C Barakat; G Debize; M Vernet; M Pouyet; J Baulieux Journal: Transplant Proc Date: 1997-11 Impact factor: 1.066
Authors: Esther B Bachli; Reto A Schuepbach; Marco Maggiorini; Reto Stocker; Beat Müllhaupt; Eberhard L Renner Journal: Liver Int Date: 2007-05 Impact factor: 5.828
Authors: Pleunie P M Rood; Rita Bottino; A N Balamurugan; Cindy Smetanka; David Ayares; Carl-Gustav Groth; Noriko Murase; David K C Cooper; Massimo Trucco Journal: Transplantation Date: 2007-01-27 Impact factor: 4.939
Authors: David K C Cooper; Anthony Dorling; Richard N Pierson; Michael Rees; Jorg Seebach; Mark Yazer; Hideki Ohdan; Michel Awwad; David Ayares Journal: Transplantation Date: 2007-07-15 Impact factor: 4.939
Authors: Raimon Duran-Struuck; Christene A Huang; Katherine Orf; Roderick T Bronson; David H Sachs; Thomas R Spitzer Journal: Comp Med Date: 2015-10 Impact factor: 0.982
Authors: L Burdorf; T Stoddard; T Zhang; E Rybak; A Riner; C Avon; A Laaris; X Cheng; E Sievert; G Braileanu; A Newton; C J Phelps; D Ayares; A M Azimzadeh; R N Pierson Journal: Am J Transplant Date: 2014-04-02 Impact factor: 8.086
Authors: Karen Kim; Christian Schuetz; Nahel Elias; Gregory R Veillette; Isaac Wamala; Manish Varma; R Neal Smith; Simon C Robson; A Benedict Cosimi; David H Sachs; Martin Hertl Journal: Xenotransplantation Date: 2012 Jul-Aug Impact factor: 3.907
Authors: N Navarro-Alvarez; J A Shah; A Zhu; J Ligocka; H Yeh; N Elias; I Rosales; R Colvin; A B Cosimi; J F Markmann; M Hertl; D H Sachs; P A Vagefi Journal: Am J Transplant Date: 2016-02-05 Impact factor: 8.086
Authors: Burcin Ekser; Christopher Burlak; Joshua P Waldman; Andrew J Lutz; Leela L Paris; Massimiliano Veroux; Simon C Robson; Michael A Rees; David Ayares; Bruno Gridelli; A Joseph Tector; David Kc Cooper Journal: Expert Rev Clin Immunol Date: 2012-09 Impact factor: 4.473