ArticleXenotransplantation
Early graft failure of GalTKO pig organs in baboons is reduced by expression of a human complement pathway-regulatory protein.
Article in Xenotransplantation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 101 citations in OpenAlex.
- Porcine kidney xenotransplantation: From primate models to clinical reality.Animal models and experimental medicine · 2026Review
- Specific pathogen free ten gene-edited donor pigs for xenotransplantation.Protein & cell · 2025Article
- Recent progress in xenotransplantation and its application to pediatric kidney disease.Pediatric nephrology (Berlin, Germany) · 2025Review
- Future Therapy for End-Stage Kidney Failure: Gene-Edited Pig Kidney Xenotransplantation.Kidney medicine · 2025Review
- Contributions of Europeans to Xenotransplantation Research: 1. Pig Organ Xenotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Genetically modified pigs with α1,3-galactosyltransferase knockout and beyond: a comprehensive review of xenotransplantation strategies.Frontiers in immunology · 2025Review
- Pig Lung Xenotransplantation: Barriers on the Road to Clinical Translation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- 2025: status of cardiac xenotransplantation including preclinical models.Frontiers in transplantation · 2025Review
- Pretransplant Screening for Prevention of Hyperacute Graft Loss in Pig-to-primate Kidney Xenotransplantation.Transplantation · 2024Article
- Complement networks in gene-edited pig xenotransplantation: enhancing transplant success and addressing organ shortage.Journal of translational medicine · 2024Review
- The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Genetic Engineering of Donor Pig for the First Human Cardiac Xenotransplantation: Combatting Rejection, Coagulopathy, Inflammation, and Excessive Growth.Current cardiology reports · 2023Review
- Cardiac Xenotransplantation: a New Frontier for Advanced Heart Failure.Current treatment options in cardiovascular medicine · 2023Article
- Preclinical rationale and current pathways to support the first human clinical trials in cardiac xenotransplantation.Human immunology · 2023Article
- The immunobiology and clinical use of genetically engineered porcine hearts for cardiac xenotransplantation.Nature cardiovascular research · 2022Article
- A desirable transgenic strategy using GGTA1 endogenous promoter-mediated knock-in for xenotransplantation model.Scientific reports · 2022Article
- Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months.Xenotransplantation · 2022Article
- Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Complement-targeted therapies in kidney transplantation-insights from preclinical studies.Frontiers in immunology · 2022Review
- Genetic engineering of pigs for xenotransplantation to overcome immune rejection and physiological incompatibilities: The first clinical steps.Frontiers in immunology · 2022Review
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Authors and funding
18 authors at 6 institutions in 1 country.
Funding
Abstract
We describe the incidence of early graft failure (EGF, defined as loss of function from any cause within 3 days after transplant) in a large cohort of GalTKO pig organs transplanted into baboons in three centers, and the effect of additional expression of a human complement pathway-regulatory protein, CD46 or CD55 (GalTKO.hCPRP). Baboon recipients of life-supporting GalTKO kidney (n = 7) or heterotopic heart (n = 14) grafts received either no immunosuppression (n = 4), or one of several partial or full immunosuppressive regimens (n = 17). Fourteen additional baboons received a GalTKO.hCPRP kidney (n = 5) or heart (n = 9) and similar treatment regimens. Immunologic, pathologic, and coagulation parameters were measured at frequent intervals. EGF of GalTKO organs occurred in 9/21 baboons (43%). hCPRP expression reduced the GalTKO EGF incidence to 7% (1/14; P < 0.01 vs. GalTKO alone). At 30 mins, complement deposits were more intense in organs in which EGF developed (P < 0.005). The intensity of peri-transplant platelet activation (as β-thromboglobulin release) correlated with EGF, as did the cumulative coagulation score (P < 0.01). We conclude that (i) the transgenic expression of a hCPRP on the vascular endothelium of a GalTKO pig reduces the incidence of EGF and reduces complement deposition, (ii) complement deposition and platelet activation correlate with early GalTKO organ failure, and (iii) the expression of a hCPRP reduces EGF but does not prevent systemic coagulation activation. Additional strategies will be required to control coagulation activation.
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Registered trials
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 Socratic graph.