NDLI: Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD/SCID/IL2rÎ³KO mice.

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Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD/SCID/IL2rÎ³KO mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ishikawa, Fumihiko Wake, Taichi Kurashima, Yosuke Suzuki, Nahoko Shultz, Leonard D. Tanaka, Satoshi Saito, Yoriko Kunisawa, Jun Kiyono, Hiroshi
Description	Country affiliation: Japan Author Affiliation: Tanaka S ( Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.)
Abstract	Although physiological development of human lymphoid subsets has become well documented in humanized mice, in vivo development of human myeloid subsets in a xenotransplantation setting has remained unevaluated. Therefore, we investigated in vivo differentiation and function of human myeloid subsets in NOD/SCID/IL2rÎ³(null) (NSG) mouse recipients transplanted with purified lineage(-)CD34(+)CD38(-) cord blood hematopoietic stem cells. At 4-6 mo posttransplantation, we identified the development of human neutrophils, basophils, mast cells, monocytes, and conventional and plasmacytoid dendritic cells in the recipient hematopoietic organs. The tissue distribution and morphology of these human myeloid cells were similar to those identified in humans. After cytokine stimulation in vitro, phosphorylation of STAT molecules was observed in neutrophils and monocytes. In vivo administration of human G-CSF resulted in the recruitment of human myeloid cells into the recipient circulation. Flow cytometry and confocal imaging demonstrated that human bone marrow monocytes and alveolar macrophages in the recipients displayed intact phagocytic function. Human bone marrow-derived monocytes/macrophages were further confirmed to exhibit phagocytosis and killing of Salmonella typhimurium upon IFN-Î³ stimulation. These findings demonstrate the development of mature and functionally intact human myeloid subsets in vivo in the NSG recipients. In vivo human myelopoiesis established in the NSG humanized mouse system may facilitate the investigation of human myeloid cell biology including in vivo analyses of infectious diseases and therapeutic interventions.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1103660
Journal	The Journal of Immunology
Issue Number	12
Volume Number	188
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Hematopoietic Stem Cell Transplantation Myeloid Cells Cytology Immunology Metabolism Transplantation, Heterologous Animals Flow Cytometry Interleukin Receptor Common Gamma Subunit Deficiency Genetics Mice Mice, Inbred Nod Mice, Knockout Mice, Scid Microscopy, Confocal Phagocytosis Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s. Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Transplantation of human spleen into immunodeficient NOD/SCID IL2RÎ³(null) mice generates humanized mice that improve functional B cell development.

Intrahepatic transplantation of cord blood CD34+ cells into newborn NOD/SCID-IL2RÎ³(null) mice allows efficient multi-organ and multi-lineage hematopoietic engraftment without accessory cells.

The effect of human fetal liver-derived mesenchymal stem cells on CD34+ hematopoietic stem cell repopulation in NOD/Shi-scid/IL-2Rã(null) mice.

Efficient xenoengraftment in severe immunodeficient NOD/Shi-scid IL2rÎ³null mice is attributed to a lack of CD11c+B220+CD122+ cells.

Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation.

Characterization of human B cells in umbilical cord blood-transplanted NOD/SCID mice.

Co-transplantation of human fetal thymus, bone and $CD34^{+}$ cells into young adult immunodeficient NOD/SCID $IL2Rγ^{null}$ mice optimizes humanized mice that mount adaptive antibody responses

Expansion in vitro of transplantable human cord blood stem cells demonstrated using a quantitative assay of their lympho-myeloid repopulating activity in nonobese diabetic-scid/scid mice.

Development of mature and functional human myeloid subsets in HSC engrafted NOD/SCID/IL2rγKO mice

Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD/SCID/IL2rÎ³KO mice.

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Transplantation of human spleen into immunodeficient NOD/SCID IL2RÎ³(null) mice generates humanized mice that improve functional B cell development.

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Development of mature and functional human myeloid subsets in HSC engrafted NOD/SCID/IL2rγKO mice

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