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. FINDINGS: 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. INTERPRETATION: 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.
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. FINDINGS: 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. INTERPRETATION: 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: 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: David K C Cooper; Burcin Ekser; Christopher Burlak; Mohamed Ezzelarab; Hidetaka Hara; Leela Paris; A Joseph Tector; Carol Phelps; Agnes M Azimzadeh; David Ayares; Simon C Robson; Richard N Pierson Journal: Xenotransplantation Date: 2012 May-Jun Impact factor: 3.907
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