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

Ekser, B and Klein, E and He, J and Stolz, DB and Echeverri, GJ and Long, C and Lin, CC and Ezzelarab, M and Hara, H and Veroux, M and Ayares, D and Cooper, DKC and Gridelli, B (2012) Genetically-engineered pig-to-baboon liver xenotransplantation: Histopathology of xenografts and native organs. PLoS ONE, 7 (1).

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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. © 2012 Ekser et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ekser, B
Klein, Eeklein@pitt.eduEKLEIN
He, J
Stolz, DBdonna.stolz@pitt.eduDSTOLZ
Echeverri, GJ
Long, Ccal46@pitt.eduCAL46
Lin, CC
Ezzelarab, Mmbe8@pitt.eduMBE8
Hara, Hhih3@pitt.eduHIH3
Veroux, M
Ayares, D
Cooper, DKCcooperdk@pitt.eduCOOPERDK
Gridelli, B
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorZimmerman, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 11 January 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 1
DOI or Unique Handle: 10.1371/journal.pone.0029720
Schools and Programs: School of Medicine > Cell Biology and Molecular Physiology
Refereed: Yes
MeSH Headings: Animals; Animals, Genetically Modified; Female; Galactosyltransferases--physiology; Genetic Engineering; Graft Rejection--immunology; Graft Rejection--pathology; Humans; Liver--immunology; Liver--pathology; Liver Failure--immunology; Liver Failure--therapy; Liver Transplantation--immunology; Liver Transplantation--pathology; Male; Papio; Sus scrofa; Transplantation, Heterologous--immunology; Transplantation, Heterologous--pathology
Other ID: NLM PMC3256162
PubMed Central ID: PMC3256162
PubMed ID: 22247784
Date Deposited: 13 Sep 2012 15:24
Last Modified: 30 Oct 2018 13:58
URI: http://d-scholarship.pitt.edu/id/eprint/14014

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