ArticleXenotransplantation2019
Porcine signal regulatory protein alpha binds to human CD47 to inhibit phagocytosis: Implications for human hematopoietic stem cell transplantation into severe combined immunodeficient 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 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Long-term engraftment of human stem and progenitor cells for large-scale production of functional immune cells in engineered pigs.Nature biomedical engineering · 2025Article
- Advances and applications of genome-edited animal models for severe combined immunodeficiency.Zoological research · 2025Review
- Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024Review
- Tolerating CD47.Clinical and translational medicine · 2024Review
- Review
- Article
- Suppressing or Enhancing Macrophage Engulfment through the Use of CD47 and Related Peptides.Bioconjugate chemistry · 2022Review
- Allogeneic and xenogeneic lymphoid reconstitution in aFrontiers in veterinary science · 2022Article
- Comparison of Genetically Engineered Immunodeficient Animal Models for Nonclinical Testing of Stem Cell Therapies.Pharmaceutics · 2021Review
- Progress towards xenogenic tolerance.Current opinion in organ transplantation · 2020Review
- Macrophage checkpoint blockade: results from initial clinical trials, binding analyses, and CD47-SIRPα structure-function.Antibody therapeutics · 2020Review
- Photosensitizer-loaded cell membrane biomimetic nanoparticles for enhanced tumor synergetic targeted therapy.RSC advances · 2020Article
- Novel Engraftment and T Cell Differentiation of Human Hematopoietic Cells inFrontiers in immunology · 2020Article
- Justification of specific genetic modifications in pigs for clinical organ xenotransplantation.Xenotransplantation · 2019Review
- Cellular Therapies for the Treatment of Hematological Malignancies; Swine Are an Ideal Preclinical Model.Frontiers in oncology · 2019Review
- Development of Severe Combined Immunodeficient (SCID) Pig Models for Translational Cancer Modeling: Future Insights on How Humanized SCID Pigs Can Improve Preclinical Cancer Research.Frontiers in oncology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSevere combined immunodeficient (SCID) pigs are an emerging animal model being developed for biomedical and regenerative medicine research. SCID pigs can successfully engraft human-induced pluripotent stem cells and cancer cell lines. The development of a humanized SCID pig through xenotransplantation of human hematopoietic stem cells (HSCs) would be a further demonstration of the value of such a large animal SCID model. Xenotransplantation success with HSCs into non-obese diabetic (NOD)-derived SCID mice is dependent on the ability of NOD mouse signal regulatory protein alpha (SIRPA) to bind human CD47, inducing higher phagocytic tolerance than other mouse strains. Therefore, we investigated whether porcine SIRPA binds human CD47 in the context of developing a humanized SCID pig.
methodsPeripheral blood mononuclear cells (PBMCs) were collected from SCID and non-SCID pigs. Flow cytometry was used to assess whether porcine monocytes could bind to human CD47. Porcine monocytes were isolated from PBMCs and were subjected to phagocytosis assays with pig, human, and mouse red blood cell (RBC) targets. Blocking phagocytosis assays were performed by incubating human RBCs with anti-human CD47 blocking antibody B6H12, non-blocking antibody 2D3, and nonspecific IgG1 antibody and exposing to human or porcine monocytes.
resultsWe found that porcine SIRPA binds to human CD47 in vitro by flow cytometric assays. Additionally, phagocytosis assays were performed, and we found that porcine monocytes phagocytose human and porcine RBCs at significantly lower levels than mouse RBCs. When human RBCs were preincubated with CD47 antibodies B6H12 or 2D3, phagocytosis was induced only after B6H12 incubation, indicating the lower phagocytic activity of porcine monocytes with human cells requires interaction between porcine SIRPA and human CD47.
conclusionsWe have shown the first evidence that porcine monocytes can bind to human CD47 and are phagocytically tolerant to human cells, suggesting that porcine SCID models have the potential to support engraftment of human HSCs.
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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.