ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2024
Extended survival of 9- and 10-gene-edited pig heart xenografts with ischemia minimization and CD154 costimulation blockade-based immunosuppression.
Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Review
- Contributions of Europeans to Xenotransplantation Research: 1. Pig Organ Xenotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- 2025: status of cardiac xenotransplantation including preclinical models.Frontiers in transplantation · 2025Review
- 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
- Xenotransplantation Literature Update July-December 2024.XenotransplantationReview
- Cellular Dynamics of Transgenic Porcine Endothelial Cells to Inflammatory Stimuli in Xenotransplantation Settings.XenotransplantationArticle
- Immunosuppressive and Non-Immunosuppressive Drugs for Heart Xenotransplantation in Humans: Is Europe Ready?XenotransplantationReview
- C-Reactive Protein as a Biomarker of Inflammation and Graft Injury After Kidney and Heart Allo- and Xenotransplantation Into Non-Human Primates.XenotransplantationArticle
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26 authors.
Funding
Abstract
backgroundXenotransplantation has made significant advances recently using pigs genetically engineered to remove carbohydrate antigens, either alone or with addition of various human complement, coagulation, and anti-inflammatory ''transgenes''. Here we evaluated results associated with gene-edited (GE) pig hearts transplanted in baboons using an established costimulation-based immunosuppressive regimen and a cold-perfused graft preservation technique.
methodsEight baboons received heterotopic abdominal heart transplants from 3-GE (GalKO.β4GalNT2KO.hCD55, n = 3), 9-GE (GalKO.β4GalNT2KO.GHRKO.hCD46.hCD55. TBM.EPCR.hCD47. HO-1, n = 3) or 10-G (9-GE+CMAHKO, n = 2) pigs using Steen's cold continuous perfusion for ischemia minimization. Immunosuppression (IS) included induction with anti-thymocyte globulin and αCD20, ongoing αCD154, MMF, and tapered corticosteroid.
resultsAll three 3-GE grafts functioned well initially, but failed within 5 days. One 9-GE graft was lost intraoperatively due to a technical issue and another was lost at POD 13 due to antibody mediated rejection (AMR) in a baboon with a strongly positive pre-operative cross-match. One 10-GE heart failed at POD113 with combined cellular and antibody mediated rejection. One 9-GE and one 10-GE hearts had preserved graft function with normal myocardium on protocol biopsies, but exhibited slowly progressive graft hypertrophy until elective necropsy at POD393 and 243 respectively. Elevated levels of IL-6, MCP-1, C-reactive protein, and human thrombomodulin were variably associated with conditioning, the transplant procedure, and clinically significant postoperative events.
conclusionRelative to reference genetics without thrombo-regulatory and anti-inflammatory gene expression, 9- or 10-GE pig hearts exhibit promising performance in the context of a clinically applicable regimen including ischemia minimization and αCD154-based IS, justifying further evaluation in an orthotopic model.
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