ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2014
Expression of human CD46 modulates inflammation associated with GalTKO lung xenograft injury.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood.XenotransplantationPooled it
- Targeted knock-in of human immune-regulatory genes into the porcine GGTA1 exon 4 reveals divergent expression on red blood cell membranes.Scientific reports · 2025Article
- Pig Lung Xenotransplantation: Barriers on the Road to Clinical Translation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Generation and characterization of genetically modified pigs with GGTA1/β4GalNT2/CMAH knockout and human CD55/CD47 expression for xenotransfusion studies.Scientific reports · 2024Article
- Future of Lung Transplantation: Xenotransplantation and Bioengineering Lungs.Clinics in chest medicine · 2023Review
- Review
- Human erythrocyte fragmentation during ex-vivo pig organ perfusion.Xenotransplantation · 2022Article
- Effects of human TFPI and CD47 expression and selectin and integrin inhibition during GalTKO.hCD46 pig lung perfusion with human blood.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
- Xenotransplantation and interspecies organogenesis: current status and issues.Frontiers in endocrinology · 2022Review
- Humanized von Willebrand factor reduces platelet sequestration in ex vivo and in vivo xenotransplant models.Xenotransplantation · 2021Article
- Minimizing Ischemia Reperfusion Injury in Xenotransplantation.Frontiers in immunology · 2021Review
- Genetically-engineered pigs as sources for clinical red blood cell transfusion: What pathobiological barriers need to be overcome?Blood reviews · 2019Review
- Thromboxane and histamine mediate PVR elevation during xenogeneic pig lung perfusion with human blood.Xenotransplantation · 2019Article
- Xenotransplantation: Current Status in Preclinical Research.Frontiers in immunology · 2019Review
- Generation of GTKO Diannan Miniature Pig Expressing Human Complementary Regulator Proteins hCD55 and hCD59 via T2A Peptide-Based Bicistronic Vectors and SCNT.Molecular biotechnology · 2018Article
- Overcoming Coagulation Dysregulation in Pig Solid Organ Transplantation in Nonhuman Primates: Recent Progress.Transplantation · 2018Review
- Interleukin-8 mediates neutrophil-endothelial interactions in pig-to-human xenogeneic models.Xenotransplantation · 2018Article
- Lung xenotransplantation.Current opinion in organ transplantation · 2017Review
- The role of sialic acids in the immune recognition of xenografts.Xenotransplantation · 2017Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Evaluation of lungs from GalTKO.hCD46 pigs, genetically modified to lack the galactose-α(1,3)-galactose epitope (GalTKO) and to express human CD46, a complement regulatory protein, has not previously been described. Physiologic, hematologic and biochemical parameters during perfusion with heparinized fresh human blood were measured for 33 GalTKO.hCD46, GalTKO (n = 16), and WT pig lungs (n = 16), and 12 pig lungs perfused with autologous pig blood. Median GalTKO.hCD46 lung survival was 171 min compared to 120 for GalTKO (p = 0.27) and 10 for WT lungs (p < 0.001). Complement activation, platelet activation and histamine elaboration were significantly reduced during the first 2 h of perfusion in GalTKO.hCD46 lungs compared to GalTKO (ΔC3a at 120' 812 ± 230 vs. 1412 ± 1047, p = 0.02; ΔCD62P at 120' 9.8 ± 7.2 vs. 25.4 ± 18.2, p < 0.01; Δhistamine at 60' 97 ± 62 vs. 189 ± 194, p = 0.03). We conclude that, in addition to significant down-modulation of complement activation, hCD46 expression in GalTKO lungs diminished platelet and coagulation cascade activation, neutrophil sequestration and histamine release. Because GalTKO.hCD46 lung failure kinetics correlated directly with platelet and neutrophil sequestration, coagulation cascade activation and a rise in histamine levels within the first hour of perfusion, further progress will likely depend upon improved control of these pathways, by rationally targeted additional modifications to pigs and pharmacologic interventions.
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Registered trials
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