Complement Depletion Improves Human Red Blood Cell Reconstitution in Immunodeficient Mice

Bing, Chen; Wei, Fan Yan; Zou, Jun; Zhang, Siwen; He, Jin; Shu, Chen; Zhao, Guoqing; Sun, Tianmeng; Hu, Zheng; Yang, Yong‐Guang

doi:10.1016/j.stemcr.2017.08.018

Cited by 20 publications

(29 citation statements)

References 33 publications

(45 reference statements)

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“…Xenograft survival in SCID animals is still limited as the remaining innate immune components are involved in rejection of human cell xenografts, independently of functional B or T cells (49, 50). Importantly, both nude and SCID animals may present a ‘leaky phenotype’, with development of some functional B and T cells arising from residual and low frequency NHEJ (51).…”

Section: Immunocompromised Modelsmentioning

confidence: 99%

Immune-relevant aspects of murine models of head and neck cancer

Rossa

D’Silva

2019

Oncogene

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Head and neck cancers (HNC) cause significant mortality and morbidity. There have been few advances in therapeutic management of HNC in the past 4 to 5 decades, which supports the need for studies focusing on HNC biology. In recent years, increased recognition of the relevance of the host response in cancer progression has led to novel therapeutic strategies and putative biomarkers of tumor aggressiveness. However, tumor-immune interactions are highly complex and vary with cancer type. Pre-clinical, in vivo models represent an important and necessary step in understanding biological processes involved in development, progression and treatment of HNC. Rodents (mice, rats, hamsters) are the most frequently used animal models in HNC research. The relevance and utility of information generated by studies in murine models is unquestionable, but it is also limited in application to tumor-immune interactions. In this review, we present information regarding the immune-specific characteristics of the murine models most commonly used in HNC research, including immunocompromised and immunocompetent animals. The particular characteristics of xenograft, chemically-induced, syngeneic, transgenic, and humanized models are discussed in order to provide context and insight for researchers interested in the in vivo study of tumor-immune interactions in HNC.

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Section: Immunocompromised Modelsmentioning

confidence: 99%

Immune-relevant aspects of murine models of head and neck cancer

Rossa

D’Silva

2019

Oncogene

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“…Previous reports in mouse models indicate NOD mouse macrophages phagocytose human RBC despite the ability of NOD SIRPA to bind to human CD47. The phagocytosis of human RBC by NOD macrophages is hypothesized to be attributed to either mouse complement or xenoantigens on the human RBCs . In our study, we were able to show low levels of in vitro phagocytosis of human RBC by porcine monocytes; enhanced phagocytosis only occurred when the porcine SIRPA‐human CD47 axis was blocked with the anti‐human CD47 B6H12 antibody.…”

Section: Discussionmentioning

confidence: 49%

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

Boettcher

Cunnick

Powell

et al. 2018

Xenotransplantation

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Background: 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.Methods: Peripheral 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. Results:We 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. AUTH O R CO NTR I B UTI O N S ANB designed and performed experiments, analyzed data, and wrote the manuscript; JEC, CLL, EJP, and TKE designed experiments, reviewed data, and edited manuscript; EJP performed statistical analysis; SEC genotyped piglets, managed SCID pig colony, and helped with sample collection; and CKT designed experiments, reviewed data, and edited manuscript. O RCI D Adeline N. Boettcher

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“…NSG-SGM3-BLT mice ( 44 )]. NSGW41, BRgWv, NBSGW and SRG-W41 mice are reported to show robust human HSPC engraftment in the absence of irradiation and this is coupled with improved human bone marrow erythropoiesis compared to irradiated NSG mice ( 4 , 36 , 38 – 40 , 43 – 45 ). Our results extend these and our own previous findings ( 29 ) by demonstrating consistent engraftment and human leucocyte reconstitution following intravenous transplantation of as few as 10x10 3 CD133 + HSPCs in adult nonirradiated NBSGW recipients over the extended period of 20-22 weeks, regardless of sex and without the requirement to co-transplant other human hematopoietic niche tissues.…”

Section: Discussionmentioning

confidence: 99%

Development of LT-HSC-Reconstituted Non-Irradiated NBSGW Mice for the Study of Human Hematopoiesis In Vivo

et al. 2021

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Humanized immune system (HIS) mouse models are useful tools for the in vivo investigation of human hematopoiesis. However, the majority of HIS models currently in use are biased towards lymphocyte development and fail to support long-term multilineage leucocytes and erythrocytes. Those that achieve successful multilineage reconstitution often require preconditioning steps which are expensive, cause animal morbidity, are technically demanding, and poorly reproducible. In this study, we address this challenge by using HSPC-NBSGW mice, in which NOD,B6.SCID IL-2rγ-/-KitW41/W41 (NBSGW) mice are engrafted with human CD133+ hematopoietic stem and progenitor cells (HSPCs) without the need for preconditioning by sublethal irradiation. These HSPCs are enriched in long-term hematopoietic stem cells (LT-HSCs), while NBSGW mice are permissive to human hematopoietic stem cell (HSC) engraftment, thus reducing the cell number required for successful HIS development. B cells reconstitute with the greatest efficiency, including mature B cells capable of class-switching following allogeneic stimulation and, within lymphoid organs and peripheral blood, T cells at a spectrum of stages of maturation. In the thymus, human thymocytes are identified at all major stages of development. Phenotypically distinct subsets of myeloid cells, including dendritic cells and mature monocytes, engraft to a variable degree in the bone marrow and spleen, and circulate in peripheral blood. Finally, we observe human erythrocytes which persist in the periphery at high levels following macrophage clearance. The HSPC-NBSGW model therefore provides a useful platform for the study of human hematological and immunological processes and pathologies.

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Complement Depletion Improves Human Red Blood Cell Reconstitution in Immunodeficient Mice

Cited by 20 publications

References 33 publications

Immune-relevant aspects of murine models of head and neck cancer

Immune-relevant aspects of murine models of head and neck cancer

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

Development of LT-HSC-Reconstituted Non-Irradiated NBSGW Mice for the Study of Human Hematopoiesis In Vivo

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