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Genetically-Engineered Pig-to-Baboon Liver Xenotransplantation: Histopathology of Xenografts and Native Organs
| Content Provider | Semantic Scholar |
|---|---|
| Author | Ekser, Burcin Klein, Edwin H. He, Jing Stolz, Donna B. Echeverri, Gabriel J. Long, Cassandra Lin, Chih Che Ezzelarab, Mohamed B. Hara, Hidetaka Veroux, Massimiliano Ayares, David Lee Cooper, David K. C. Gridelli, Bruno G. |
| Copyright Year | 2012 |
| 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. |
| File Format | PDF HTM / HTML |
| DOI | 10.1371/journal.pone.0029720 |
| PubMed reference number | 22247784 |
| Journal | Medline |
| Volume Number | 7 |
| Alternate Webpage(s) | http://ftp.ncbi.nlm.nih.gov/pub/pmc/84/44/pone.0029720.PMC3256162.pdf |
| Alternate Webpage(s) | http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0029720&type=printable |
| Alternate Webpage(s) | http://www.westlaboratory.org/wp-content/uploads/2011/05/Ekser-2012-Genetically-Engineered-Pig-to-Baboon-Liver-Xenotransplantation-Oct-1.pdf |
| Alternate Webpage(s) | http://d-scholarship.pitt.edu/14014/1/Genetically-Engineered_Pig.pdf |
| Alternate Webpage(s) | https://doi.org/10.1371/journal.pone.0029720 |
| Journal | PloS one |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
