ArticleXenotransplantation2021
Expression of human CD47 in pig glomeruli prevents proteinuria and prolongs graft survival following pig-to-baboon xenotransplantation.
Article in Xenotransplantation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Progress in immunological research on innate effectors in xenotransplantation.Surgery today · 2026Review
- Porcine kidney xenotransplantation: From primate models to clinical reality.Animal models and experimental medicine · 2026Review
- Present Advances and Emerging Challenges in Kidney Xenotransplantation.Journal of clinical medicine · 2026Review
- Xeno kidney: revolutionizing kidney disease treatment.Frontiers in nephrology · 2026Review
- Review
- Modern xenotransplantation: rewiring glycan-mediated immunogenicity via genome-glycome convergence.EBioMedicine · 2026Review
- 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
- Specific pathogen free ten gene-edited donor pigs for xenotransplantation.Protein & cell · 2025Article
- Progressive Hyperglycemia in Tolerant Miniature Swine Recipients of Composite Islet-kidney Grafts Is not due to Islet Loss but Rather to Increased Insulin Demand With Growth.Transplantation · 2025Article
- Plasma exchange and intravenous immunoglobulin prolonged the survival of a porcine kidney xenograft in a sensitized, brain-dead human recipient.Chinese medical journal · 2025Article
- Current status and prospects of genetically modified porcine-to-human cardiac xenotransplantation.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2025Review
- Progress in Porcine Kidney Transplantation to Non-Human Primates.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Recent progress in pig-to-human kidney xenotransplantation.Frontiers in immunology · 2025Review
- Research prospects for kidney xenotransplantation: a bibliometric analysis.Renal failure · 2024Article
- Pretransplant Screening for Prevention of Hyperacute Graft Loss in Pig-to-primate Kidney Xenotransplantation.Transplantation · 2024Article
- Physiological basis for xenotransplantation from genetically modified pigs to humans.Physiological reviews · 2024Review
- The Contributions of Thrombospondin-1 to Epilepsy Formation.Neuroscience bulletin · 2024Review
- Tolerating CD47.Clinical and translational medicine · 2024Review
- De novo membranous nephropathy in a pig-to-baboon kidney xenograft: A new xenograft glomerulopathy.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024Article
- Genetic Engineering of Donor Pig for the First Human Cardiac Xenotransplantation: Combatting Rejection, Coagulopathy, Inflammation, and Excessive Growth.Current cardiology reports · 2023Review
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15 authors at 4 institutions in 2 countries.
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Abstract
backgroundNephrotic syndrome is a common complication of pig-to-baboon kidney xenotransplantation (KXTx) that adversely affects outcomes. We have reported that upregulation of CD80 and down-regulation of SMPDL-3b in glomeruli have an important role in the development of proteinuria following pig-to-baboon KXTx. Recently we found induced expression of human CD47 (hCD47) on endothelial cells and podocytes isolated from hCD47 transgenic (Tg) swine markedly reduced phagocytosis by baboon and human macrophages. These observations led us to hypothesize that transplanting hCD47 Tg porcine kidneys could overcome the incompatibility of the porcine CD47-baboon SIRPα interspecies ligand-receptor interaction and prevent the development of proteinuria following KXTx.
methodsTen baboons received pig kidneys with vascularized thymic grafts (n = 8) or intra-bone bone marrow transplants (n = 2). Baboons were divided into three groups (A, B, and C) based on the transgenic expression of hCD47 in GalT-KO pigs. Baboons in Group A received kidney grafts with expression of hCD47 restricted to glomerular cells (n = 2). Baboons in Group B received kidney grafts with high expression of hCD47 on both glomerular and tubular cells of the kidneys (n = 4). Baboons in Group C received kidney grafts with low/no glomerular expression of hCD47, and high expression of hCD47 on renal tubular cells (n = 4).
resultsConsistent with this hypothesis, GalT-KO/hCD47 kidney grafts with high expression of hCD47 on glomerular cells developed minimal proteinuria. However, high hCD47 expression in all renal cells including renal tubular cells induced an apparent destructive inflammatory response associated with upregulated thrombospondin-1. This response could be avoided by a short course of weekly anti-IL6R antibody administration, resulting in prolonged survival without proteinuria (mean 170.5 days from 47.8 days).
conclusionData showed that transgenic expression of hCD47 on glomerular cells in the GalT-KO donor kidneys can prevent xenograft nephropathy, a significant barrier for therapeutic applications of xenotransplantation. The ability to prevent nephrotic syndrome following KXTx overcomes a critical barrier for future clinical applications of KXTx.
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