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Immunological and physiological observations in baboons with life-supporting genetically engineered pig kidney grafts
| Content Provider | Scilit |
|---|---|
| Author | Iwase, Hayato Hara, Hidetaka Ezzelarab, Mohamed Li, Tao Zhang, Zhongqiang Gao, Bingsi Liu, Hong Long, Cassandra Wang, Yi Cassano, Amy Klein, Edwin Phelps, Carol Ayares, David Humar, Abhinav Wijkstrom, Martin Cooper, David K. C. |
| Copyright Year | 2017 |
| Description | Journal: Xenotransplantation Genetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310 days, but graft survival >30 days has been unusual until recently. Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein. Two baboons received a kidney from a six-gene pig (GroupA) and two from a three-gene pig (GroupB). Immunosuppressive therapy was identical in all four cases and consisted of anti-thymoglobulin (ATG)+anti-CD20mAb (induction) and anti-CD40mAb+rapamycin+corticosteroids (maintenance). Anti-TNF-α and anti-IL-6R mAbs were administered to reduce the inflammatory response. Baboons were followed by clinical/laboratory monitoring of immune/coagulation/inflammatory/physiological parameters. At biopsy or euthanasia, the grafts were examined by microscopy. The two GroupA baboons remained healthy with normal renal function >7 and >8 months, respectively, but then developed infectious complications. However, no features of a consumptive coagulopathy, eg, thrombocytopenia and reduction of fibrinogen, or of a protein-losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response, and histology of biopsies taken at approximately 4, 6, and 7 months and at necropsy showed no significant abnormalities. In contrast, both GroupB baboons developed features of a consumptive coagulopathy and required euthanasia on day 12. The combination of (i) a graft from a specific six-gene genetically modified pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory therapy prevented immune injury, a protein-losing nephropathy, and coagulation dysfunction for >7 months. Although the number of experiments is very limited, our impression is that expression of human endothelial protein C receptor (±CD55) in the graft is important if coagulation dysregulation is to be avoided. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397334/pdf |
| e-ISSN | 13993089 |
| DOI | 10.1111/xen.12293 |
| Journal | Xenotransplantation |
| Issue Number | 2 |
| Volume Number | 24 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2017-03-17 |
| Access Restriction | Open |
| Subject Keyword | Journal: Xenotransplantation Anti-il-6r Antagonist Costimulation Blockade Genetically Engineered Xenotransplantation |
| Content Type | Text |
| Resource Type | Article |
