Hepatic function after genetically engineered pig liver transplantation in baboons

Burcin Ekser, Gabriel J. Echeverri, Andrea Cortese Hassett, Mark H. Yazer, Cassandra Long, Michael Meyer, Mohamed Ezzelarab, Chih Che Lin, Hidetaka Hara, Dirk J. Van Der Windt, Eefje M. Dons, Carol Phelps, David Ayares, David K C Cooper, Bruno Gridelli

Research output: Contribution to journalArticle

51 Citations (Scopus)

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 α1,3-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.

Original languageEnglish
Pages (from-to)483-493
Number of pages11
JournalTransplantation
Volume90
Issue number5
DOIs
Publication statusPublished - Sep 15 2010

Fingerprint

Papio
Liver Transplantation
Swine
Liver
Blood Coagulation Factors
Proteins
Western Blotting
Galactosyltransferases
Gene Knockout Techniques
Haptoglobins
Plasminogen
Liver Function Tests
Cholestasis
Heterografts
Thrombocytopenia
Fibrinogen
Albumins
Reference Values
Transplantation
Hemorrhage

Keywords

  • α1,3-Galactosylransferase gene-knockout
  • Acute liver failure
  • Baboon
  • Coagulation
  • Coagulation factors
  • Genetically modified
  • Liver
  • Pig
  • Xenotransplantation

ASJC Scopus subject areas

  • Transplantation
  • Medicine(all)

Cite this

Ekser, B., Echeverri, G. J., Hassett, A. C., Yazer, M. H., Long, C., Meyer, M., ... Gridelli, B. (2010). Hepatic function after genetically engineered pig liver transplantation in baboons. Transplantation, 90(5), 483-493. https://doi.org/10.1097/TP.0b013e3181e98d51

Hepatic function after genetically engineered pig liver transplantation in baboons. / Ekser, Burcin; Echeverri, Gabriel J.; Hassett, Andrea Cortese; Yazer, Mark H.; Long, Cassandra; Meyer, Michael; Ezzelarab, Mohamed; Lin, Chih Che; Hara, Hidetaka; Van Der Windt, Dirk J.; Dons, Eefje M.; Phelps, Carol; Ayares, David; Cooper, David K C; Gridelli, Bruno.

In: Transplantation, Vol. 90, No. 5, 15.09.2010, p. 483-493.

Research output: Contribution to journalArticle

Ekser, B, Echeverri, GJ, Hassett, AC, Yazer, MH, Long, C, Meyer, M, Ezzelarab, M, Lin, CC, Hara, H, Van Der Windt, DJ, Dons, EM, Phelps, C, Ayares, D, Cooper, DKC & Gridelli, B 2010, 'Hepatic function after genetically engineered pig liver transplantation in baboons', Transplantation, vol. 90, no. 5, pp. 483-493. https://doi.org/10.1097/TP.0b013e3181e98d51
Ekser B, Echeverri GJ, Hassett AC, Yazer MH, Long C, Meyer M et al. Hepatic function after genetically engineered pig liver transplantation in baboons. Transplantation. 2010 Sep 15;90(5):483-493. https://doi.org/10.1097/TP.0b013e3181e98d51
Ekser, Burcin ; Echeverri, Gabriel J. ; Hassett, Andrea Cortese ; Yazer, Mark H. ; Long, Cassandra ; Meyer, Michael ; Ezzelarab, Mohamed ; Lin, Chih Che ; Hara, Hidetaka ; Van Der Windt, Dirk J. ; Dons, Eefje M. ; Phelps, Carol ; Ayares, David ; Cooper, David K C ; Gridelli, Bruno. / Hepatic function after genetically engineered pig liver transplantation in baboons. In: Transplantation. 2010 ; Vol. 90, No. 5. pp. 483-493.
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AU - Long, Cassandra

AU - Meyer, Michael

AU - Ezzelarab, Mohamed

AU - Lin, Chih Che

AU - Hara, Hidetaka

AU - Van Der Windt, Dirk J.

AU - Dons, Eefje M.

AU - Phelps, Carol

AU - Ayares, David

AU - Cooper, David K C

AU - Gridelli, Bruno

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N2 - 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 α1,3-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.

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KW - Liver

KW - Pig

KW - Xenotransplantation

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