ArticleThe Journal of thoracic and cardiovascular surgery2014
Genetically engineered pigs and target-specific immunomodulation provide significant graft survival and hope for clinical cardiac xenotransplantation.
Article in The Journal of thoracic and cardiovascular surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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.
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
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 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
- Orthotopic liver xenotransplantation from gene-modified pig to decedent human.Nature biomedical engineering · 2026Article
- Pediatric partial heart xenotransplantation as an early use case of xenograft tissue.Future cardiology · 2025Review
- Cardiac transplantation: A review of current status and emerging innovations.World journal of transplantation · 2025Review
- Genetically engineered pig heart transplantation in non-human primates.Communications medicine · 2025Article
- Animal models for transplant immunology: bridging bench to bedside.Clinical transplantation and research · 2024Review
- Combination of Anti-CD40 and Anti-CD40L Antibodies as Co-Stimulation Blockade in Preclinical Cardiac Xenotransplantation.Biomedicines · 2024Article
- Prolonged xenokidney graft survival in sensitized NHP recipients by expression of multiple human transgenes in a triple knockout pig.Science translational medicine · 2024Article
- Animal models for partial heart transplantation.Pediatric transplantation · 2024Review
- What Genetic Modifications of Source Pigs Are Essential and Sufficient for Cell, Tissue, and Organ Xenotransplantation?Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Progress in Orthotopic Pig Heart Transplantation in Nonhuman Primates.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report.Lancet (London, England) · 2023Article
- Comparison of Bovine- and Porcine-Derived Decellularized Biomaterials: Promising Platforms for Tissue Engineering Applications.Pharmaceutics · 2023Article
- Review
- The history of cardiac xenotransplantation: early attempts, major advances, and current progress.Frontiers in transplantation · 2023Review
- Review
- The potential of genetically engineered pig heart transplantation in infants with complex congenital heart disease.Pediatric transplantation · 2022Review
- Cardiac Xenotransplantation: Challenges, Evolution, and Advances.JACC. Basic to translational science · 2022Review
- Evolution of Xenotransplantation as an Alternative to Shortage of Donors in Heart Transplantation.Cureus · 2022Review
- Genetic engineering of pigs for xenotransplantation to overcome immune rejection and physiological incompatibilities: The first clinical steps.Frontiers in immunology · 2022Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesCardiac transplantation and available mechanical alternatives are the only possible solutions for end-stage cardiac disease. Unfortunately, because of the limited supply of human organs, xenotransplantation may be the ideal method to overcome this shortage. We have recently seen significant prolongation of heterotopic cardiac xenograft survival from 3 to 12 months and beyond.
methodsHearts from genetically engineered piglets that were alpha 1-3 galactosidase transferase knockout and expressed the human complement regulatory gene, CD46 (groups A-C), and the human thrombomodulin gene (group D) were heterotropically transplanted in baboons treated with antithymocyte globulin, cobra venom factor, anti-CD20 antibody, and costimulation blockade (anti-CD154 antibody [clone 5C8]) in group A, anti-CD40 antibody (clone 3A8; 20 mg/kg) in group B, clone 2C10R4 (25 mg/kg) in group C, or clone 2C10R4 (50 mg/kg) in group D, along with conventional nonspecific immunosuppressive agents.
resultsGroup A grafts (n = 8) survived for an average of 70 days, with the longest survival of 236 days. Some animals in this group (n = 3) developed microvascular thrombosis due to platelet activation and consumption, which resulted in spontaneous hemorrhage. The median survival time was 21 days in group B (n = 3), 80 days in group C (n = 6), and more than 200 days in group D (n = 5). Three grafts in group D are still contracting well, with the longest ongoing graft survival surpassing the 1-year mark.
conclusionsGenetically engineered pig hearts (GTKOhTg.hCD46.hTBM) with modified targeted immunosuppression (anti-CD40 monoclonal antibody) achieved long-term cardiac xenograft survival. This potentially paves the way for clinical xenotransplantation if similar survival can be reproduced in an orthotopic transplantation model.
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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 OpenQuestion graph.