ArticleXenotransplantation2020
Transgenic expression of human CD47 reduces phagocytosis of porcine endothelial cells and podocytes by baboon and human macrophages.
Article in Xenotransplantation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Progress in immunological research on innate effectors in xenotransplantation.Surgery today · 2026Review
- Present Advances and Emerging Challenges in Kidney Xenotransplantation.Journal of clinical medicine · 2026Review
- Transplantation immunology: paradigm shift from systemic suppression to microenvironment remodeling and precision modulation.Frontiers in cell and developmental biology · 2026Review
- Neu5Gc and beyond: sialylation at the innate immune and thromboinflammatory interface of xenotransplantation.Frontiers in transplantation · 2026Review
- Review
- Hemolysis-induced hepatic ferroptosis following xenotransfusion of genetically modified pig red blood cells.Scientific reports · 2025Article
- 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
- Plasma exchange and intravenous immunoglobulin prolonged the survival of a porcine kidney xenograft in a sensitized, brain-dead human recipient.Chinese medical journal · 2025Article
- Production and Functional Verification of 8-Gene (GGTA1, CMAH, β4GalNT2, hCD46, hCD55, hCD59, hTBM, hCD39)-Edited Donor Pigs for Xenotransplantation.Cell proliferation · 2025Article
- [Research and application progress for liver xenotransplantation].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Immunoprotection Strategies in β-Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Enhancing Kidney Transplantation and the Role of Xenografts: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2024Review
- Tolerating CD47.Clinical and translational medicine · 2024Review
- Activation of immune signals during organ transplantation.Signal transduction and targeted therapy · 2023Review
- Developments in kidney xenotransplantation.Frontiers in immunology · 2023Review
- Article
- 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
- Current status of xenotransplantation research and the strategies for preventing xenograft rejection.Frontiers in immunology · 2022Review
- Interleukin-27 in liver xenotransplantation: A rational target to mitigate ischemia reperfusion injury and increase xenograft survival.Transplantation reviews (Orlando, Fla.) · 2022Review
- Cellular Immune Responses in Islet Xenograft Rejection.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundOur initial studies utilizing a galactosyl-α1-3-galactosyltransferase gene knockout (GalTKO) pig-to-baboon renal transplant model demonstrated that the early development of nephrotic syndrome has been a significant obstacle to the long-term survival of baboon recipients. We have recently documented that sphingomyelin phosphodiesterase-3 (SMPDL3b) and CD80 expressed on podocytes in porcine kidney grafts contribute to this complication. We have hypothesized that one regulator of immune function is CD47 and that incompatibilities in CD47 between pig and baboon could potentially affect macrophage function, increasing the susceptibility of the kidney grafts to immunologically induced injury.
methodsIn order to address this hypothesis in vitro, we isolated and cultured porcine podocytes and ECs from GalTKO alone, human CD47 (hCD47)/hCD55 expressing transgenic (Tg) GalTKO swine, and GalTKO hCD46/hCD55 Tg swine along with baboon or human macrophages.
resultsWe found that baboon macrophages phagocytosed porcine ECs in a similar manner to human macrophages, and this response was significantly reduced when porcine ECs and podocytes expressed hCD47/hCD55 but not hCD46/hCD55 without hCD47. Furthermore, masking hCD47 by anti-hCD47 antibody on hCD47/hCD55Tg ECs restored phagocytosis. These results are consistent with the hypothesis that CD47 incompatibility plays an important role in promoting macrophage phagocytosis of endogenous cells from the transplanted kidney.
conclusionsThe similar levels of phagocytosis of porcine cells by baboon and human macrophages suggest that the expression of hCD47Tg on glomerular cells in donor porcine kidneys may prove to be a key strategy for preventing proteinuria following kidney xenotransplantation in a pig-to-human as well as a pig-to-baboon 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.