Genetically-engineered pig-to-baboon liver xenotransplantation: Histopathology of xenografts and native organs

Burcin Ekser, Edwin Klein, Jing He, Donna B. Stolz, Gabriel J. Echeverri, Cassandra Long, Chih Che Lin, Mohamed Ezzelarab, Hidetaka Hara, Massimiliano Veroux, David Ayares, David K C Cooper, Bruno Gridelli

Research output: Contribution to journalArticle

Abstract

Orthotopic liver transplantation was carried out in baboons using wild-type (WT, n = 1) or genetically-engineered pigs (α1,3-galactosyltransferase gene-knockout, GTKO), n = 1; GTKO pigs transgenic for human CD46, n = 7) and a clinically-acceptable immunosuppressive regimen. Biopsies were obtained from the WT pig liver pre-Tx and at 30 min, 1, 2, 3, 4 and 5 h post-transplantation. Biopsies of genetically-engineered livers were obtained pre-Tx, 2 h after reperfusion and at necropsy (4-7 days after transplantation). Tissues were examined by light, confocal, and electron microscopy. All major native organs were also examined. The WT pig liver underwent hyperacute rejection. After genetically-engineered pig liver transplantation, hyperacute rejection did not occur. Survival was limited to 4-7 days due to repeated spontaneous bleeding in the liver and native organs (as a result of profound thrombocytopenia) which necessitated euthanasia. At 2 h, graft histology was largely normal. At necropsy, genetically-engineered pig livers showed hemorrhagic necrosis, platelet aggregation, platelet-fibrin thrombi, monocyte/macrophage margination mainly in liver sinusoids, and vascular endothelial cell hypertrophy, confirmed by confocal and electron microscopy. Immunohistochemistry showed minimal deposition of IgM, and almost absence of IgG, C3, C4d, C5b-9, and of a cellular infiltrate, suggesting that neither antibody- nor cell-mediated rejection played a major role.

Original languageEnglish
Article numbere29720
JournalPLoS One
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 11 2012

Fingerprint

xenotransplantation
Heterologous Transplantation
Papio
Heterografts
histopathology
Liver
Swine
liver
swine
galactosyltransferases
Galactosyltransferases
liver transplant
Gene Knockout Techniques
gene targeting
Confocal Microscopy
Liver Transplantation
Biopsy
Confocal microscopy
biopsy
necropsy

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ekser, B., Klein, E., He, J., Stolz, D. B., Echeverri, G. J., Long, C., ... Gridelli, B. (2012). Genetically-engineered pig-to-baboon liver xenotransplantation: Histopathology of xenografts and native organs. PLoS One, 7(1), [e29720]. https://doi.org/10.1371/journal.pone.0029720

Genetically-engineered pig-to-baboon liver xenotransplantation : Histopathology of xenografts and native organs. / Ekser, Burcin; Klein, Edwin; He, Jing; Stolz, Donna B.; Echeverri, Gabriel J.; Long, Cassandra; Lin, Chih Che; Ezzelarab, Mohamed; Hara, Hidetaka; Veroux, Massimiliano; Ayares, David; Cooper, David K C; Gridelli, Bruno.

In: PLoS One, Vol. 7, No. 1, e29720, 11.01.2012.

Research output: Contribution to journalArticle

Ekser, B, Klein, E, He, J, Stolz, DB, Echeverri, GJ, Long, C, Lin, CC, Ezzelarab, M, Hara, H, Veroux, M, Ayares, D, Cooper, DKC & Gridelli, B 2012, 'Genetically-engineered pig-to-baboon liver xenotransplantation: Histopathology of xenografts and native organs', PLoS One, vol. 7, no. 1, e29720. https://doi.org/10.1371/journal.pone.0029720
Ekser, Burcin ; Klein, Edwin ; He, Jing ; Stolz, Donna B. ; Echeverri, Gabriel J. ; Long, Cassandra ; Lin, Chih Che ; Ezzelarab, Mohamed ; Hara, Hidetaka ; Veroux, Massimiliano ; Ayares, David ; Cooper, David K C ; Gridelli, Bruno. / Genetically-engineered pig-to-baboon liver xenotransplantation : Histopathology of xenografts and native organs. In: PLoS One. 2012 ; Vol. 7, No. 1.
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