ArticleTransplantation2016
Silencing Porcine CMAH and GGTA1 Genes Significantly Reduces Xenogeneic Consumption of Human Platelets by Porcine Livers.
Article in Transplantation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 42 citations in OpenAlex.
- Variability of Sialic Acids in Beef Breeds and Nutritional Implications in Red Meat.Molecules (Basel, Switzerland) · 2025Article
- CRISPR Technology Acts as a Dual-Purpose Tool in Pig Breeding: Enhancing Both Agricultural Productivity and Biomedical Applications.Biomolecules · 2024Review
- 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
- Human immune reactivity of GGTA1/CMAH/A3GALT2 triple knockout Yucatan miniature pigs.Transgenic research · 2021Article
- CRISPR/Cas Technology in Pig-to-Human Xenotransplantation Research.International journal of molecular sciences · 2021Review
- A review of pig liver xenotransplantation: Current problems and recent progress.Xenotransplantation · 2019Review
- Genome editing in large animals: current status and future prospects.National science review · 2019Article
- Xenotransplantation: Current Status in Preclinical Research.Frontiers in immunology · 2019Review
- [Research progress of producing genetically modified pigs by CRISPR/Cas9 in the medical field].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2018Review
- Xenotransplantation: past, present, and future.Current opinion in organ transplantation · 2017Review
- N-glycolylneuraminic acid knockout reduces erythrocyte sequestration and thromboxane elaboration in an ex vivo pig-to-human xenoperfusion model.Xenotransplantation · 2017Article
- The role of sialic acids in the immune recognition of xenografts.Xenotransplantation · 2017Review
- Genetically Modified Pigs as Organ Donors for Xenotransplantation.Molecular biotechnology · 2017Review
- Resection or transplantation for hepatocellular carcinoma: is the decision clear for patients beyond Milan criteria?Hepatobiliary surgery and nutrition · 2017Article
- Selection of Patients for Initial Clinical Trials of Solid Organ Xenotransplantation.Transplantation · 2017Review
- Pig Liver Xenotransplantation: A Review of Progress Toward the Clinic.Transplantation · 2016Review
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Authors and funding
10 authors at 1 institution in 3 countries.
Funding
Abstract
backgroundA profound thrombocytopenia limits hepatic xenotransplantation in the pig-to-primate model. Porcine livers also have shown the ability to phagocytose human platelets in the absence of immune-mediated injury. Recently, inactivation of the porcine ASGR1 gene has been shown to decrease this phenomenon. Inactivating GGTA1 and CMAH genes has reduced the antibody-mediated barrier to xenotransplantation; herein, we describe the effect that these modifications have on xenogeneic consumption of human platelets in the absence of immune-mediated graft injury.
methodsWild type (WT), ASGR1, GGTA1, and GGTA1CMAH knockout pigs were compared for their xenogeneic hepatic consumption of human platelets. An in vitro assay was established to measure the association of human platelets with liver sinusoidal endothelial cells (LSECs) by immunohistochemistry. Perfusion models were used to measure human platelet uptake in livers from WT, ASGR1, GGTA1, and GGTA1 CMAH pigs.
resultsGGTA1, CMAH LSECs exhibited reduced levels of human platelet binding in vitro when compared with GGTA1 and WT LSECs. In a continuous perfusion model, GGTA1 CMAH livers consumed fewer human platelets than GGTA1 and WT livers. GGTA1 CMAH livers also consumed fewer human platelets than ASGR1 livers in a single-pass model.
conclusionsSilencing the porcine carbohydrate genes necessary to avoid antibody-mediated rejection in a pig-to-human model also reduces the xenogeneic consumption of human platelets by the porcine liver. The combination of these genetic modifications may be an effective strategy to limit the thrombocytopenia associated with pig-to-human hepatic xenotransplantation.
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