ArticleXenotransplantation2017
Immunological and physiological observations in baboons with life-supporting genetically engineered pig kidney grafts.
Article in Xenotransplantation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 214 citations in OpenAlex.
- Porcine kidney xenotransplantation: From primate models to clinical reality.Animal models and experimental medicine · 2026Review
- Progress of transgenic pigs in liver xenotransplantation.Liver research (Beijing, China) · 2026Article
- Xeno kidney: revolutionizing kidney disease treatment.Frontiers in nephrology · 2026Review
- Development of a BM7G(TKO/hCD46/hCD55/hTHBD/hEPCR) donor pig with endogenous promoter-driven transgenes for xenotransplantation.Frontiers in immunology · 2026Article
- Physiologic Homeostasis in a Living Human after Pig Kidney Xenotransplantation.Nature communications · 2025Article
- Article
- Future Therapy for End-Stage Kidney Failure: Gene-Edited Pig Kidney Xenotransplantation.Kidney medicine · 2025Review
- Characterizing coagulation responses in humans and nonhuman primates following kidney xenotransplantation-A narrative review.American journal of hematology · 2025Review
- Antibodies to unknown antigens other than swine leukocyte antigens on GTKO/β4GalNT2KO pig cells are associated with AHXR after pig-to-rhesus monkey kidney transplantation.Frontiers in immunology · 2025Article
- Epitope-level analysis of cross-reactive human HLA antibodies against genetically modified swine leukocyte antigens in xenotransplantation.Frontiers in immunology · 2025Article
- Swine clones: potential application for animal production and animal models.Animal reproduction · 2025Review
- Genetically modified pigs with α1,3-galactosyltransferase knockout and beyond: a comprehensive review of xenotransplantation strategies.Frontiers in immunology · 2025Review
- Generation and characterization of genetically modified pigs with GGTA1/β4GalNT2/CMAH knockout and human CD55/CD47 expression for xenotransfusion studies.Scientific reports · 2024Article
- Research prospects for kidney xenotransplantation: a bibliometric analysis.Renal failure · 2024Article
- Pretransplant Screening for Prevention of Hyperacute Graft Loss in Pig-to-primate Kidney Xenotransplantation.Transplantation · 2024Article
- Ethics, virtues and xenotransplantation.Perfusion · 2024Review
- Chimeric Livers: Interspecies Blastocyst Complementation and Xenotransplantation for End-Stage Liver Disease.Hepatic medicine : evidence and research · 2024Review
- Complement, Coagulation, and Fibrinolysis: The Role of the Endothelium and Its Glycocalyx Layer in Xenotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Cutting edge of immune response and immunosuppressants in allogeneic and xenogeneic islet transplantation.Frontiers in immunology · 2024Review
- Genetic Engineering of Donor Pig for the First Human Cardiac Xenotransplantation: Combatting Rejection, Coagulopathy, Inflammation, and Excessive Growth.Current cardiology reports · 2023Review
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundGenetically 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.
methodsDonor 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.
resultsThe 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.
conclusionsThe 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.