Humanized SCID Mouse Models for Biomedical Research

Pearson, Todd; Greiner, Dale L.; Shultz, Leonard D.

doi:10.1007/978-3-540-75647-7_2

Cited by 84 publications

(88 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with reports that humanized mice support diversified xenogeneic hematopoiesis (23,24), analysis of huCD45 + BM cells 1 mo after grafting detected cells expressing lymphoid T (CD7), B (CD10, CD19), or NK (CD56) markers, as well as discrete erythromegakaryocytic (CD36, GPA, CD41) and monocytic (CD14) cell subsets (data not shown). CD34 + HPCs (median, 25%; range, 16-39%) were segregated into two CD34 lacked CD7, CD10, CD19, and CD33 markers, suggesting that they comprised most multipotent progenitors (Fig.…”

Section: Resultssupporting

confidence: 87%

Dynamics of Human Prothymocytes and Xenogeneic Thymopoiesis in Hematopoietic Stem Cell-Engrafted Nonobese Diabetic-SCID/IL-2rγnull Mice

Parietti

Nelson

Telliam

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

To model the developmental pattern of human prothymocytes and thymopoiesis, we used NOD-scid/γc−/− mice grafted with human umbilical cord blood CD34+ hematopoietic progenitor cells (HPCs). Human prothymocytes developed in the murine bone marrow (BM) from multipotent CD34++CD38lolineage− HPCs to CD34++CD7+CD2- pro-T1 cells that progressed in a Notch-dependent manner to CD34+CD7++CD2+ pro-T2 cells, which migrated to the thymus. BM prothymocyte numbers peaked 1 mo after graft, dropped at mo 2, and persisted at low levels thereafter, with only a few CD34+CD7lo prothymocytes with limited T potential being detected by mo 5. As a consequence, thymopoiesis in this xenogeneic setting began by weeks 4–6, peaked at mo 3, and decreased thenceforth. Analyzing mice grafted at 2, 4 or 8, mo of age showed that in an “older” BM, prothymocyte differentiation was perturbed and resulted in CD34+CD7lo prothymocytes with limited T potential. Whereas the early drop in BM thymopoietic activity was related to a Notch-independent loss of T potential by CD34++CD38lolineage− HPCs, the later age-dependent production decline of prothymocytes was linked to a more complex mix of cell-intrinsic and microenvironmental defects. Accordingly, and contrasting with what was observed with umbilical cord blood HPCs, CD34+ HPCs from human adult BM displayed only marginal thymopoietic activity when grafted into young 2-mo-old NOD-scid/γc−/− mice. These data demonstrate that the developmental pattern of BM prothymocytes during human late fetal and early postnatal life can be reproduced in humanized mice, and they suggest that onset of human thymus involution relates to decreased colonization by prothymocytes.

show abstract

Section: Resultssupporting

confidence: 87%

Dynamics of Human Prothymocytes and Xenogeneic Thymopoiesis in Hematopoietic Stem Cell-Engrafted Nonobese Diabetic-SCID/IL-2rγnull Mice

Parietti

Nelson

Telliam

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…As shown by different groups, NSG mice are a valuable tool for studying numerous immune-related diseases, such as GvHD, and for the research on novel therapeutic strategies (23,33,34). It seems likely that induction of GvHD is more severe in a xenogeneic transplantation setting (human PBMCs into NSG mice) than after allogeneic transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, most of these therapeutic approaches depend on intravenous application to the recipients and antibodies are often highly immunogenic (19,21). Potent tools to study immunological pathologies such as GvHD in vivo are NOD.Cg-Prkdc scid IL-2rg tm1Wjl /SzJ (NSG) mice, an immunosuppressed strain bearing a mutation in the IL-2 receptor common gamma chain (IL-2Rc) gene (22,23). NSG mice have an impaired adaptive immune system as well as defective NKcell development, allowing human immune cells to engraft and provoke GvHD (24)(25)(26).…”

mentioning

confidence: 99%

Attenuation of graft‐versus‐host‐disease in NOD scid IL‐2Rγ^−/− (NSG) mice by ex vivo modulation of human CD4⁺ T cells

et al. 2016

View full text Add to dashboard Cite

NOD.Cg-Prkdcscid IL-2rg tm1Wjl /SzJ (NSG) mice are a valuable tool for studying Graftversus-Host-Disease (GvHD) induced by human immune cells. We used a model of acute GvHD by transfer of human peripheral blood mononuclear cells (PBMCs) into NSG mice. The severity of GvHD was reflected by weight loss and was associated with engraftment of human cells and the expansion of leukocytes, particularly granulocytes and monocytes. Pre-treatment of PBMCs with the anti-human CD4 antibody MAX.16H5 IgG1 or IgG4 attenuated GvHD. The transplantation of 2 3 10 7 PBMCs without anti-human CD4 pre-treatment induced a severe GvHD (0% survival). In animals receiving 2 3 10 7 PBMCs pre-incubated with MAX.16H5 IgG1 or IgG4, GvHD development was reduced and survival was increased. Immune reconstitution was measured by flow cytometry and confirmed for human leukocytes (CD45), CD3 /CD41 T helper cells. Human B cells (CD19) and monocytes (CD14) could not be detected. Histopathological analysis (TUNEL assay) of the gut of recipient animals showed significantly less apoptotic crypt cells in animals receiving a MAX.16H5 IgG1 pre-incubated graft. These findings indicate that preincubation of an allogeneic graft with an anti-human CD4 antibody may decrease the frequency and severity of GvHD after hematopoietic stem cell transplantation (HSCT) and the need of conventional immunosuppressive drugs. Moreover, this approach most probably provides a safer HSCT that must be confirmed in appropriate clinical trials in the future. V C 2016 International Society for Advancement of Cytometry

show abstract

“…administration of freshly isolated cells versus cells expanded in culture (24 h in StemSpan SFEM medium with CC100 Cytokine Cocktail); 84,85 . tail vein versus intrafemoral cell injection; 86,87 . with or without human IL-15/IL-15Ra complex treatment at 6 and 7 weeks of age and at day 6.5 after mating.…”

Section: Il2rgmentioning

confidence: 99%

Natural killer cell-triggered vascular transformation: maternal care before birth?

et al. 2010

View full text Add to dashboard Cite

Natural killer (NK) cells are found in lymphoid and non-lymphoid organs. In addition to important roles in immune surveillance, some NK cells contribute to angiogenesis and circulatory regulation. The uterus of early pregnancy is a non-lymphoid organ enriched in NK cells that are specifically recruited to placental attachment sites. In species with invasive hemochorial placentation, these uterine natural killer (uNK) cells, via secretion of cytokines, chemokines, mucins, enzymes and angiogenic growth factors, contribute to the physiological change of mesometrial endometrium into the unique stromal environment called decidua basalis. In humans, uNK cells have the phenotype CD56 bright CD16 dim and they appear in great abundance in the late secretory phase of the menstrual cycle and early pregnancy. Gene expression studies indicate that CD56 bright CD16 dim uterine and circulating cells are functionally distinct. In humans but not mice or other species with post-implantation decidualization, uNK cells may contribute to blastocyst implantation and are of interest as therapeutic targets in female infertility. Histological and genetic studies in mice first identified triggering of the process of gestation spiral arterial modification as a major uNK cell function, achieved via interferon (IFN)-c secretion. During spiral arterial modification, branches from the uterine artery that traverse the endometrium/decidua transiently lose their muscular coat and ability to vasoconstrict. The expression of vascular markers changes from arterial to venous as these vessels dilate and become low-resistance, high-volume channels. Full understanding of the vascular interactions of human uNK cells is difficult to obtain because endometrial time-course studies are not possible in pregnant women. Here we briefly review key information concerning uNK cell functions from studies in rodents, summarize highlights concerning human uNK cells and describe our preliminary studies on development of a humanized, pregnant mouse model for in vivo investigations of human uNK cell functions.

show abstract

Humanized SCID Mouse Models for Biomedical Research

Cited by 84 publications

References 135 publications

Dynamics of Human Prothymocytes and Xenogeneic Thymopoiesis in Hematopoietic Stem Cell-Engrafted Nonobese Diabetic-SCID/IL-2rγnull Mice

Dynamics of Human Prothymocytes and Xenogeneic Thymopoiesis in Hematopoietic Stem Cell-Engrafted Nonobese Diabetic-SCID/IL-2rγnull Mice

Attenuation of graft‐versus‐host‐disease in NOD scid IL‐2Rγ^−/− (NSG) mice by ex vivo modulation of human CD4⁺ T cells

Natural killer cell-triggered vascular transformation: maternal care before birth?

Contact Info

Product

Resources

About

Humanized SCID Mouse Models for Biomedical Research

Cited by 84 publications

References 135 publications

Dynamics of Human Prothymocytes and Xenogeneic Thymopoiesis in Hematopoietic Stem Cell-Engrafted Nonobese Diabetic-SCID/IL-2rγnull Mice

Dynamics of Human Prothymocytes and Xenogeneic Thymopoiesis in Hematopoietic Stem Cell-Engrafted Nonobese Diabetic-SCID/IL-2rγnull Mice

Attenuation of graft‐versus‐host‐disease in NOD scid IL‐2Rγ−/− (NSG) mice by ex vivo modulation of human CD4+ T cells

Natural killer cell-triggered vascular transformation: maternal care before birth?

Contact Info

Product

Resources

About

Attenuation of graft‐versus‐host‐disease in NOD scid IL‐2Rγ^−/− (NSG) mice by ex vivo modulation of human CD4⁺ T cells