ArticleXenotransplantation2019
The role of human CD46 in early xenoislet engraftment in a dual transplant model.
Article in Xenotransplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- 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
- Complement and T cell activation in transplantation.Transplantation reviews (Orlando, Fla.) · 2025Review
- Immunoprotection Strategies in β-Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Complement networks in gene-edited pig xenotransplantation: enhancing transplant success and addressing organ shortage.Journal of translational medicine · 2024Review
- Metabolic effect of low fluoride levels in the islets of NOD mice: integrative morphological, immunohistochemical, and proteomic analyses.Journal of applied oral science : revista FOB · 2023Article
- Clinically available immunosuppression averts rejection but not systemic inflammation after porcine islet xenotransplant in cynomolgus macaques.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Immune-Protective Formulations and Process Strategies for Improved Survival and Function of Transplanted Islets.Frontiers in immunology · 2022Review
- Current Topics of Relevance to the Xenotransplantation of Free Pig Islets.Frontiers in immunology · 2022Review
- Role of Complement System in Kidney Transplantation: Stepping From Animal Models to Clinical Application.Frontiers in immunology · 2022Review
- Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival.Xenotransplantation · 2021Article
- Coagulation, inflammation, and CD46 transgene expression in neonatal porcine islet xenotransplantation.Xenotransplantation · 2021Article
- Donor-Derived Cell-Free DNA (dd-cfDNA) as an Early Noninvasive Biomarker of Graft Injury in Pig-to-Monkey Islet Xenotransplantation.XenotransplantationArticle
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMembrane cofactor protein CD46 attenuates the complement cascade by facilitating cleavage of C3b and C4b. In solid organ xenotransplantation, organs expressing CD46 have been shown to resist hyperacute rejection. However, the incremental value of human CD46 expression for islet xenotransplantation remains poorly defined.
methodsThis study attempted to delineate the role of CD46 in early neonatal porcine islet engraftment by comparing Gal-knocked out (GKO) and hCD46-transgenic (GKO/CD46) islets in a dual transplant model. Seven rhesus macaques underwent dual transplant and were sacrificed at 1 hour (n = 4) or 24 hours (n = 3). Both hemilivers were recovered and fixed for immunohistochemistry (CD46, insulin, neutrophil elastase, platelet, IgM, IgG, C3d, C4d, CD68, Caspase 3). Quantitative immunohistochemical analysis was performed using the Aperio Imagescope.
resultsWithin 1 hour of intraportal infusion of xenografts, no differences were observed between the two types of islets in terms of platelet, antibody, or complement deposition. Cellular infiltration and islet apoptotic activity were also similar at 1 hour. At 24 hours, GKO/CD46 islets demonstrated significantly less platelet deposition (P = 0.01) and neutrophil infiltration (P = 0.01) compared to GKO islets. In contrast, C3d (P = 0.38) and C4d (P = 0.45) deposition was equal between the two genotypes.
conclusionsOur findings suggest that expression of hCD46 on NPIs potentially provides a measurable incremental survival advantage in vivo by reducing early thrombo-inflammatory events associated with instant blood-mediated inflammatory reaction (IBMIR) following intraportal islet infusion.
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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.