ArticleXenotransplantation
Pig-to-baboon liver xenoperfusion utilizing GalTKO.hCD46 pigs and glycoprotein Ib blockade.
Article in Xenotransplantation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Systematic Review and Comparative Outcomes Analysis of NHP Liver Allotransplants and Xenotransplants.XenotransplantationPooled it
- Bibliometric analysis of liver xenotransplantation (2005-2025): trends, challenges and future directions.Updates in surgery · 2026Article
- Genetically engineered porcine liver: a new era in transplantation.International journal of surgery (London, England) · 2026Article
- Graft-derived VWF drives platelet activation and thrombocytopenia during porcine liver xenotransplantation to brain-dead human recipients.The Journal of clinical investigation · 2026Article
- Liver Xenotransplantation: From Early Primate Trials to the First-in-Human Porcine Bridging Therapies.Journal of clinical medicine · 2026Review
- Extracorporeal liver cross-circulation using transgenic xenogeneic pig livers with brain-dead human decedents.Nature medicine · 2026Article
- hEPCR.hTBM.hCD47.hHO-1 with donor clodronate and DDAVP treatment improves perfusion and function of GalTKO.hCD46 porcine livers perfused with human blood.Xenotransplantation · 2022Article
- Current Barriers to Clinical Liver Xenotransplantation.Frontiers in immunology · 2022Review
- Humanized von Willebrand factor reduces platelet sequestration in ex vivo and in vivo xenotransplant models.Xenotransplantation · 2021Article
- Novel alternative transplantation therapy for orthotopic liver transplantation in liver failure: A systematic review.World journal of transplantation · 2020Article
- A review of pig liver xenotransplantation: Current problems and recent progress.Xenotransplantation · 2019Review
- N-glycolylneuraminic acid knockout reduces erythrocyte sequestration and thromboxane elaboration in an ex vivo pig-to-human xenoperfusion model.Xenotransplantation · 2017Article
- The production of multi-transgenic pigs: update and perspectives for xenotransplantation.Transgenic research · 2016Review
- Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor.Xenotransplantation · 2016Article
- An Immunological and Translational Framework for Interspecies Exogenic Liver Transplantation.Cell transplantationReview
- Expression of Human Thrombomodulin Prevents Early Thrombocytopenia and Thrombotic Microangiopathy in Pig-to-Nonhuman Primate Orthotopic Liver Xenotransplantation.XenotransplantationArticle
- Expression of human thrombomodulin by GalTKO.hCD46 pigs modulates coagulation cascade activation by endothelial cells and during ex vivo lung perfusion with human blood.XenotransplantationArticle
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAlthough transplantation of genetically modified porcine livers into baboons has yielded recipient survival for up to 7 days, survival is limited by profound thrombocytopenia, which becomes manifest almost immediately after revascularization, and by subsequent coagulopathy. Porcine von Willebrand's factor (VWF), a glycoprotein that adheres to activated platelets to initiate thrombus formation, has been shown to constitutively activate human platelets via their glycoprotein Ib (GPIb) receptors. Here, we report our pig-to-primate liver xenoperfusion model and evaluate whether targeting the GPIb-VWF axis prevents platelet sequestration.
methodsTwelve baboons underwent cross-circulation with the following extracorporeal livers: one allogeneic control with a baboon liver, 4 xenogeneic controls with a GalTKO.hCD46 pig liver, 3 GalTKO.hCD46 pig livers in recipients treated with αGPIb antibody during perfusion, and 4 GalTKO.hCD46 pig livers pre-treated with D-arginine vasopressin (DDAVP) in recipients treated with αGPIb antibody during perfusion.
resultsAll perfused livers appeared grossly and macroscopically normal and produced bile. Xenograft liver perfusion experiments treated with αGPIb antibody may show less platelet sequestration during the initial 2 h of perfusion. Portal venous resistance remained constant in all perfusion experiments. Platelet activation studies demonstrated platelet activation in all xenoperfusions, but not in the allogeneic perfusion.
conclusionThese observations suggest that primate platelet sequestration by porcine liver and the associated thrombocytopenia are multifactorial and perhaps partially mediated by a constitutive interaction between porcine VWF and the primate GPIb receptor. Control of platelet sequestration and consumptive coagulopathy in liver xenotransplantation will likely require a multifaceted approach in our clinically relevant perfusion model.
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