Porcine signal regulatory protein alpha binds to human CD47 to inhibit phagocytosis: Implications for human hematopoietic stem cell transplantation into severe combined immunodeficient pigs

Severe 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.

• Publication year

  2018

• Venue

  Xenotransplantation

• Publication date

  2018-10-12

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/xen.12466PMID 30311702PMCID PMC7717580
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Creating effective biocontainment facilities and maintenance protocols for raising specific pathogen-free, severe combined immunodeficient (SCID) pigs

  2018cited by this paper
• Humanized Mouse Models of Clinical Disease.

  2017cited by this paper
• Complement Depletion Improves Human Red Blood Cell Reconstitution in Immunodeficient Mice

  2017cited by this paper
• SCID pigs: An emerging large animal NK model.

  2017cited by this paper
• T Cell Lymphoma and Leukemia in Severe Combined Immunodeficiency Pigs following Bone Marrow Transplantation: A Case Report

  2017cited by this paper
• Role of Human CD200 Overexpression in Pig-to-Human Xenogeneic Immune Response Compared With Human CD47 Overexpression

  2017cited by this paper
• Increased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency

  2016cited by this paper
• Pigs with Severe Combined Immunodeficiency Are Impaired in Controlling Influenza A Virus Infection

  2016cited by this paper
• Engineered Swine Models of Cancer

  2016cited by this paper
• Biallelic modification of IL2RG leads to severe combined immunodeficiency in pigs

  2016cited by this paper
• Comparative Analysis of piggyBac, CRISPR/Cas9 and TALEN Mediated BAC Transgenesis in the Zygote for the Generation of Humanized SIRPA Rats

  2016cited by this paper
• Generation and characterization of RAG2 knockout pigs as animal model for severe combined immunodeficiency.

  2016cited by this paper
• NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene.

  2016cited by this paper
• Abstract 2470: Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies

  2015cited by this paper
• Livestock models in translational medicine.

  2015cited by this paper
• Not All SCID Pigs Are Created Equally: Two Independent Mutations in the Artemis Gene Cause SCID in Pigs

  2015cited by this paper
• Cell rigidity and shape override CD47's "self"-signaling in phagocytosis by hyperactivating myosin-II.

  2015cited by this paper
• Xenograft Tolerance and Immune Function of Human T Cells Developing in Pig Thymus Xenografts

  2014cited by this paper
• Influence of a dual-injection regimen, plerixafor and CXCR4 on in utero hematopoietic stem cell transplantation and engraftment with use of the sheep model.

  2014cited by this paper
• The interaction between signal regulatory protein alpha (SIRPα) and CD47: structure, function, and therapeutic target.

  2014cited by this paper
• Animal versus human oral drug bioavailability: Do they correlate?

  2014cited by this paper
• The BALB/c-specific polymorphic SIRPA enhances its affinity for human CD47, inhibiting phagocytosis against human cells to promote xenogeneic engraftment.

  2014cited by this paper
• Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency

  2014cited by this paper
• Signal-regulatory protein α from the NOD mouse binds human CD47 with an exceptionally high affinity – implications for engraftment of human cells

  2014cited by this paper
• Genomic responses in mouse models poorly mimic human inflammatory diseases

  2013cited by this paper
• Polymorphic Sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment.

  2013cited by this paper
• Anti-CD47 antibody–mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response

  2013cited by this paper
• Structural and functional annotation of the porcine immunome

  2013cited by this paper
• Differences in human and porcine platelet oligosaccharides may influence phagocytosis by liver sinusoidal cells in vitro

  2012cited by this paper
• The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

  2012cited by this paper
• Human Xenografts Are Not Rejected in a Naturally Occurring Immunodeficient Porcine Line: A Human Tumor Model in Pigs

  2012cited by this paper
• Il2rg gene-targeted severe combined immunodeficiency pigs.

  2012cited by this paper
• CD47 functions as a molecular switch for erythrocyte phagocytosis.

  2012cited by this paper
• Transgenic expression of human signal regulatory protein alpha in Rag2−/−γc−/− mice improves engraftment of human hematopoietic cells in humanized mice

  2011cited by this paper
• Macrophages prevent human red blood cell reconstitution in immunodeficient mice.

  2011cited by this paper
• Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic leukemia.

  2011cited by this paper
• The pig: a model for human infectious diseases

  2011cited by this paper
• Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega

  2011cited by this paper
• The mononuclear phagocyte system of the pig as a model for understanding human innate immunity and disease

  2011cited by this paper
• Humanized mouse models to study human diseases

  2010cited by this paper
• Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma.

  2010cited by this paper
• The fate of human platelets perfused through the pig liver: implications for xenotransplantation

  2010cited by this paper
• Signal regulatory protein alpha (SIRPalpha)/CD47 interaction and function.

  2009cited by this paper
• CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells.

  2009cited by this paper
• Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47.

  2008cited by this paper
• Toward Development and Production of Human T Cells in Swine for Potential Use in Adoptive T Cell Immunotherapy

  2008cited by this paper
• Novel structural determinants on SIRP alpha that mediate binding to CD47.

  2007cited by this paper
• Functional elements on SIRPalpha IgV domain mediate cell surface binding to CD47.

  2007cited by this paper
• The Structure of the Macrophage Signal Regulatory Protein α (SIRPα) Inhibitory Receptor Reveals a Binding Face Reminiscent of That Used by T Cell Receptors*

  2007cited by this paper
• Novel Structural Determinants on SIRPα that Mediate Binding to CD471

  2007cited by this paper
• Role for CD47-SIRPα signaling in xenograft rejection by macrophages

  2007cited by this paper
• Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells

  2007cited by this paper
• The structure of the macrophage signal regulatory protein alpha (SIRPalpha) inhibitory receptor reveals a binding face reminiscent of that used by T cell receptors.

  2007cited by this paper
• Macrophage tolerance: CD47-SIRP-alpha-mediated signals matter.

  2007cited by this paper
• Macrophage tolerance: CD47–SIRP-α–mediated signals matter

  2007cited by this paper
• Role for CD47-SIRPalpha signaling in xenograft rejection by macrophages.

  2007cited by this paper
• Functional Elements on SIRPα IgV domain Mediate Cell Surface Binding to CD47

  2007cited by this paper
• Species- and cell type-specific interactions between CD47 and human SIRPalpha.

  2006cited by this paper
• Successful multilineage engraftment of human cord blood cells in pigs after in utero transplantation

  2003cited by this paper
• Role of CD47 as a marker of self on red blood cells.

  2000cited by this paper
• Integrin-associated Protein Is a Ligand for the P84 Neural Adhesion Molecule*

  1999cited by this paper
• Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

  1997cited by this paper

• Cell membrane-coated nanoparticles-based drug delivery systems for osteoarthritis therapy: the application and potential translation into clinical therapy

  2025cites this paper
• Hypoimmunogenic human motor neurons induced from iPSCs in vivo substantially ameliorate ALS disease in large animal models

  2025cites this paper
• Human Hematopoietic Stem Cell Engraftment and Differentiation in Immunodeficient Pigs

  2025cites this paper
• Long-term engraftment of human stem and progenitor cells for large-scale production of functional immune cells in engineered pigs

  2025influential citation
• Advances and applications of genome-edited animal models for severe combined immunodeficiency

  2025cites this paper
• Tolerating CD47

  2024influential citation
• Erythrocyte Membrane Coating Alleviate Immune Response and Promoted Adipogenesis in Adipose Matrix

  2024cites this paper
• Deciphering the role of CD47 in cancer immunotherapy

  2023cites this paper
• Porcine Macrophage Markers and Populations: An Update

  2023cites this paper
• Suppressing or Enhancing Macrophage Engulfment through the Use of CD47 and Related Peptides.

  2022cites this paper
• Red blood cell membrane nanoparticles for tumor phototherapy.

  2022cites this paper
• Allogeneic and xenogeneic lymphoid reconstitution in a RAG2−/−IL2RGy/− severe combined immunodeficient pig: A preclinical model for intrauterine hematopoietic transplantation

  2022cites this paper
• Comparison of Genetically Engineered Immunodeficient Animal Models for Nonclinical Testing of Stem Cell Therapies

  2021cites this paper
• CD47 cross-dressing by extracellular vesicles expressing CD47 inhibits phagocytosis without transmitting cell death signals

  2021cites this paper
• Macrophage checkpoint blockade: results from initial clinical trials, binding analyses, and CD47-SIRPα structure–function

  2020cites this paper
• Photosensitizer-loaded cell membrane biomimetic nanoparticles for enhanced tumor synergetic targeted therapy

  2020cites this paper
• Humanization of Immunodeficient Animals for the Modeling of Transplantation, Graft Versus Host Disease, and Regenerative Medicine

  2020cites this paper
• Progress towards xenogenic tolerance

  2020cites this paper
• Novel Engraftment and T Cell Differentiation of Human Hematopoietic Cells in ART−/− IL2RG−/Y SCID Pigs

  2020cites this paper
• Novel engraftment and T cell differentiation of human hematopoietic cells in Art-/- IL2RG-/ SCID pigs

  2019cites this paper
• Cellular Therapies for the Treatment of Hematological Malignancies; Swine Are an Ideal Preclinical Model

  2019cites this paper
• Xenotransplantation literature update, March/April 2019

  2019cites this paper
• Justification of specific genetic modifications in pigs for clinical organ xenotransplantation

  2019cites this paper
• Development of Severe Combined Immunodeficient (SCID) Pig Models for Translational Cancer Modeling: Future Insights on How Humanized SCID Pigs Can Improve Preclinical Cancer Research

  2018cites this paper