ArticleXenotransplantation2019
Cardiac xenografts show reduced survival in the absence of transgenic human thrombomodulin expression in donor pigs.
Article in Xenotransplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- Multiple human transgenes prolong survival of triple-carbohydrate knockout porcine kidney xenografts in nonhuman primates.Nature communications · 2026Article
- Neu5Gc and beyond: sialylation at the innate immune and thromboinflammatory interface of xenotransplantation.Frontiers in transplantation · 2026Review
- Modern xenotransplantation: rewiring glycan-mediated immunogenicity via genome-glycome convergence.EBioMedicine · 2026Review
- Pancreatic tissue engineering: towards a vascularized bioengineered cure for diabetes.Frontiers in transplantation · 2026Review
- Revolutionizing medicine: Exploring the breakthroughs in liver xenotransplantation.Liver research (Beijing, China) · 2025Review
- Cardiac transplantation: A review of current status and emerging innovations.World journal of transplantation · 2025Review
- 2025: status of cardiac xenotransplantation including preclinical models.Frontiers in transplantation · 2025Review
- Genetic Engineering of Donor Pig for the First Human Cardiac Xenotransplantation: Combatting Rejection, Coagulopathy, Inflammation, and Excessive Growth.Current cardiology reports · 2023Review
- Graft rejection in paediatric congenital heart disease.Translational pediatrics · 2023Review
- Cardiac Xenotransplantation: a New Frontier for Advanced Heart Failure.Current treatment options in cardiovascular medicine · 2023Article
- The history of cardiac xenotransplantation: early attempts, major advances, and current progress.Frontiers in transplantation · 2023Review
- Preclinical rationale and current pathways to support the first human clinical trials in cardiac xenotransplantation.Human immunology · 2023Article
- Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy.Frontiers in cell and developmental biology · 2023Review
- Progress in xenotransplantation: overcoming immune barriers.Nature reviews. Nephrology · 2022Review
- The immunobiology and clinical use of genetically engineered porcine hearts for cardiac xenotransplantation.Nature cardiovascular research · 2022Article
- Genetically Modified Porcine-to-Human Cardiac Xenotransplantation.The New England journal of medicine · 2022Article
- 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
- Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months.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
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
A combination of genetic manipulations of donor organs and target-specific immunosuppression is instrumental in achieving long-term cardiac xenograft survival. Recently, results from our preclinical pig-to-baboon heterotopic cardiac xenotransplantation model suggest that a three-pronged approach is successful in extending xenograft survival: (a) α-1,3-galactosyl transferase (Gal) gene knockout in donor pigs (GTKO) to prevent Gal-specific antibody-mediated rejection; (b) transgenic expression of human complement regulatory proteins (hCRP; hCD46) and human thromboregulatory protein thrombomodulin (hTBM) to avoid complement activation and coagulation dysregulation; and (c) effective induction and maintenance of immunomodulation, particularly through co-stimulation blockade of CD40-CD40L pathways with anti-CD40 (2C10R4) monoclonal antibody (mAb). Using this combination of manipulations, we reported significant improvement in cardiac xenograft survival. In this study, we are reporting the survival of cardiac xenotransplantation recipients (n = 3) receiving xenografts from pigs without the expression of hTBM (GTKO.CD46). We observed that all grafts underwent rejection at an early time point (median 70 days) despite utilization of our previously reported successful immunosuppression regimen and effective control of non-Gal antibody response. These results support our hypothesis that transgenic expression of human thrombomodulin in donor pigs confers an independent protective effect for xenograft survival in the setting of a co-stimulation blockade-based immunomodulatory regimen.
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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.