SynthesisXenotransplantation
Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood.
Synthesis in Xenotransplantation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed.
- Characterizing coagulation responses in humans and nonhuman primates following kidney xenotransplantation-A narrative review.American journal of hematology · 2025Review
- Pig Lung Xenotransplantation: Barriers on the Road to Clinical Translation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Prolonged xenokidney graft survival in sensitized NHP recipients by expression of multiple human transgenes in a triple knockout pig.Science translational medicine · 2024Article
- Human erythrocyte fragmentation during ex-vivo pig organ perfusion.Xenotransplantation · 2022Article
- 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
- Minimizing Ischemia Reperfusion Injury in Xenotransplantation.Frontiers in immunology · 2021Review
- Progress Toward Cardiac Xenotransplantation.Circulation · 2020Review
- Review
- Improved production of GTKO/hCD55/hCD59 triple-gene-modified Diannan miniature pigs for xenotransplantation by recloning.Transgenic research · 2020Article
- The complex functioning of the complement system in xenotransplantation.Xenotransplantation · 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
- Immunological and physiological observations in baboons with life-supporting genetically engineered pig kidney grafts.Xenotransplantation · 2017Article
- Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species.Current transplantation reports · 2017Review
- Postneonatal Mortality and Liver Changes in Cloned Pigs Associated with Human Tumor Necrosis Factor Receptor I-Fc and Human Heme Oxygenase-1 Overexpression.BioMed research international · 2017Article
- Lung xenotransplantation: a review.Current opinion in organ transplantation · 2016Review
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Authors and funding
11 authors.
Funding
Abstract
backgroundGenetically modified pigs are a promising potential source of lung xenografts. Ex vivo xenoperfusion is an effective platform for testing the effect of new modifications, but typical experiments are limited by testing of a single genetic intervention and small sample sizes. The purpose of this study was to analyze the individual and aggregate effects of donor genetic modifications on porcine lung xenograft survival and injury in an extensive pig lung xenoperfusion series.
methodsData from 157 porcine lung xenoperfusion experiments using otherwise unmodified heparinized human blood were aggregated as either continuous or dichotomous variables. Lungs were wild type in 17 perfusions (11% of the study group), while 31 lungs (20% of the study group) had one genetic modification, 40 lungs (39%) had 2, and 47 lungs (30%) had 3 or more modifications. The primary endpoint was functional lung survival to 4 h of perfusion. Secondary analyses evaluated previously identified markers associated with known lung xenograft injury mechanisms. In addition to comparison among all xenografts grouped by survival status, a subgroup analysis was performed of lungs incorporating the GalTKO.hCD46 genotype.
resultsEach increase in the number of genetic modifications was associated with additional prolongation of lung xenograft survival. Lungs that exhibited survival to 4 h generally had reduced platelet activation and thrombin generation. GalTKO and the expression of hCD46, HO-1, hCD55, or hEPCR were associated with improved survival. hTBM, HLA-E, and hCD39 were associated with no significant effect on the primary outcome.
conclusionThis meta-analysis of an extensive lung xenotransplantation series demonstrates that increasing the number of genetic modifications targeting known xenogeneic lung injury mechanisms is associated with incremental improvements in lung survival. While more detailed mechanistic studies are needed to explore the relationship between gene expression and pathway-specific injury and explore why some genes apparently exhibit neutral (hTBM, HLA-E) or inconclusive (CD39) effects, GalTKO, hCD46, HO-1, hCD55, and hEPCR modifications were associated with significant lung xenograft protection. This analysis supports the hypothesis that multiple genetic modifications targeting different known mechanisms of xenograft injury will be required to optimize lung xenograft survival.
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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.