The SCID-hu Mouse: Murine Model for the Analysis of Human Hematolymphoid Differentiation and Function

McCune, JM; Namikawa, Reiko; Kaneshima, Hideto; Shultz, L D; Lieberman, Miriam; Il, Weissman

doi:10.1126/science.2971269

Cited by 1,306 publications

(732 citation statements)

References 41 publications

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“…[19][20][21] Briefly, femurs, tibias and fibulas of 17-to 18-gestational-week-old fetuses (Advanced Bioscience Resources; Alameda, CA, USA) were implanted subcutaneously into 6-8 week-old mice. After 4 weeks, patient bone marrow cells in PBS supplemented with 25% high protein Matrigel (BD Biosciences) were transplanted directly into human bone grafts.…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

Anti-CD47 antibodies promote phagocytosis and inhibit the growth of human myeloma cells

et al. 2012

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Multiple myeloma is a plasma cell neoplasm residing in bone marrow. Despite advances in myeloma therapies, novel therapies are required to improve patient outcomes. CD47 is highly expressed on myeloma cells and a potential therapeutic candidate for myeloma therapies. Flow cytometric analysis of patient bone marrow cells revealed that myeloma cells overexpress CD47 when compared with non-myeloma cells in 73% of patients (27/37). CD47 expression protects cells from phagocytosis by transmitting an inhibitory signal to macrophages. Here we show that blocking CD47 with an anti-CD47 monoclonal antibody increased phagocytosis of myeloma cells in vitro. In xenotransplantation models, anti-CD47 antibodies inhibited the growth of RPMI 8226 myeloma cells and led to tumor regression (42/57 mice), implicating the eradication of myeloma-initiating cells. Moreover, anti-CD47 antibodies retarded the growth of patient myeloma cells and alleviated bone resorption in human bone-bearing mice. Irradiation of mice before myeloma cell xenotransplantation abolished the therapeutic efficacy of anti-CD47 antibodies delivered 2 weeks after radiation, and coincided with a reduction of myelomonocytic cells in spleen, bone marrow and liver. These results are consistent with the hypothesis that anti-CD47 blocking antibodies inhibit myeloma growth, in part, by increasing phagocytosis of myeloma cells.

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Section: Flow Cytometric Analysismentioning

confidence: 99%

Anti-CD47 antibodies promote phagocytosis and inhibit the growth of human myeloma cells

et al. 2012

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“…To confirm our in vitro results in the human in vivo system, we used mice with severe combined immunodeficiency (SCID). Recent studies have demonstrated that the SCID mouse has several defects in both humoral and cellmediated immunity, and can serve as a recipient of grafts derived from a variety of human tissues, [22][23][24][25][26][27] including rheumatoid synovium. Thus, proliferative rheumatoid synovium can grow as a xenograft in SCID mice and pre- serve the histologic components of rheumatoid synovia.…”

Section: Figure 4 Immunohistochemical Analysis Of the Effects Of Hfasmentioning

confidence: 99%

Induction of apoptosis in the rheumatoid synovium by Fas ligand gene transfer

et al. 1998

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We have recently reported that local administration of antiactivity against RA synoviocytes via the Fas/FasL system Fas monoclonal antibody (MAb) in human T cell leukemia in vitro. Histopathological and immunohistochemical studvirus type 1 (HTLV-1) carrying mice improved arthritis due ies showed that local injection of irradiated-hFasL transfecto the induction of apoptosis. This finding strongly indicated tants eliminated synoviocytes and mononuclear cells in the beneficial therapeutic effect of Fas-mediated apoptosis engrafted human rheumatoid synovium of SCID-RA mice. in rheumatoid arthritis (RA). To establish further the theraFurthermore, in situ nick end labeling analysis confirmed peutic effect of Fas-mediated apoptosis on RA taking into that the cells in engrafted synovium frequently underwent consideration safety and practicality, we investigated the apoptosis by irradiated-hFasL transfectants. Our results effect of cells transfected with human Fas ligand (hFasL) clearly demonstrated that hFasL transfectants induced gene on proliferating human rheumatoid synovium apoptosis by cell-to-cell interaction via the Fas/FasL sysengrafted in severe combined immunodeficiency (SCIDtem. Thus, ex vivo gene transfer of FasL may represent a RA) mice. The hFasL transfectants exhibited cytotoxic novel therapeutic strategy for RA.

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“…The severe combined immunodeficient (SCID)-hu Thy/Liv mouse has an intact human thymus organ, thus allowing investigation of HIV-1 pathogenesis in a human lymphoid organ. [4][5][6] However, very low levels of human T cells are detected in the peripheral lymphoid organs or blood. The hu-peripheral blood lymphocyte (PBL)-SCID mouse supports transient and selective engraftment of xenoreactive human T cells.…”

mentioning

confidence: 99%

HIV-1 infection and pathogenesis in a novel humanized mouse model

Zhang

Kovalev

2006

Blood

128

136

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IntroductionThe hallmarks of AIDS are high levels of HIV-1 infection, depletion of CD4 ϩ T cells, and loss of immunity. The mechanism of HIV-1 immunopathogenesis is not clear because human patients are the only hosts that support high levels of HIV-1 replication and develop AIDS. Extensive studies have been performed in primate models with either low levels of HIV-1 replication (HIV-1 in chimps) or a different virus (simian immunodeficiency virus [SIV] or simian/human immunodeficiency virus [SHIV] in monkeys). 1-3 HIV-1 fails to infect murine cells due to blocks at multiple steps of the HIV life cycle. The mouse with a reconstituted human immune system would be an ideal small animal model for studying HIV-1 infection and pathogenesis. A number of human-mouse chimeric models have been developed, but with only limited success. The severe combined immunodeficient (SCID)-hu Thy/Liv mouse has an intact human thymus organ, thus allowing investigation of HIV-1 pathogenesis in a human lymphoid organ. [4][5][6] However, very low levels of human T cells are detected in the peripheral lymphoid organs or blood. The hu-peripheral blood lymphocyte (PBL)-SCID mouse supports transient and selective engraftment of xenoreactive human T cells. 7,8 Human CD34 ϩ cells transplanted into SCID or nonobese diabetic (NOD)/SCID mice lead to generation of mainly human myeloid and B cells in the mouse bone marrow, but inefficient generation of human T cells. 9,10 When CD34 ϩ human hematopoietic stem cells (HSCs)/hematopoietic stem progenitor cells (HSPCs) are injected directly into the liver of newborn Rag2-␥C double-knockout (DKO) mice, which lack T, B, and natural killer (NK) cells, the newborn liver environment of DKO mice supports efficient engraftment and development of a functional human immune system in central and peripheral lymphoid organs. 11,12 To demonstrate that the DKO-hu HSC mouse can support efficient HIV-1 infection with relevant immunopathogenesis, we show that CCR5 and CXCR4, the HIV-1 coreceptors, are both expressed on human T cells in central and peripheral lymphoid organs. DKO-hu HSC mice allow high plasma viremia with high levels of HIV-1 infection in lymphoid organs. Both CD4 ϩ CD45RO ϩ and CD4 ϩ CD45RO Ϫ T cells are productively infected in lymphoid organs. Human CD4 ϩ T cells are gradually depleted by HIV-1 in a dose-dependent manner. In addition, HIV-1 infection persists in infected DKO-hu HSC mice for at least 19 weeks, with recoverable infectious HIV-1 in lymphoid tissues. Materials and methods Construction of DKO-hu HSC mice with human CD34 ؉/؊ cells from cord blood or fetal liverHuman CD34 ϩ cells were isolated from cord blood (CB) or fetal liver (FL) tissues. FL CD34 ϩ (1 ϫ 10 6 ) or CB CD34 ϩ (1 ϫ 10 5 ) cells were injected intrahepatically into each newborn DKO mouse previously irradiated at 400 rad. 11 Human leukocytes (CD45 ϩ ) were analyzed for CD3, CD4, CD8, CD45RO, CD19, CCR5(2D7), and CXCR4(12G5) by fluorescenceactivated cell sorting (FACS). 13 HIV-1 infection and pathogenesis in DKO-hu HSC miceAt l...

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The SCID-hu Mouse: Murine Model for the Analysis of Human Hematolymphoid Differentiation and Function

Cited by 1,306 publications

References 41 publications

Anti-CD47 antibodies promote phagocytosis and inhibit the growth of human myeloma cells

Anti-CD47 antibodies promote phagocytosis and inhibit the growth of human myeloma cells

Induction of apoptosis in the rheumatoid synovium by Fas ligand gene transfer

HIV-1 infection and pathogenesis in a novel humanized mouse model

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