Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/γc−/−, Balb/c-Rag1−/−γc−/−, and C.B-17-scid/bg immunodeficient mice

Lepus, Christin M.; Gibson, Thomas F.; Gerber, Scott A.; Kawikova, Ivana; Szczepanik, Marian; Hossain, Jaber; Ablamunits, Vitaly; Kirkiles-Smith, Nancy C.; Herold, Kevan C.; Donis, Ruben O.; Bothwell, Alfred L.M.; Pober, Jordan S.; Harding, Mark J.

doi:10.1016/j.humimm.2009.06.005

Cited by 108 publications

(114 citation statements)

References 45 publications

(52 reference statements)

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“…To experimentally recapitulate human immune reconstitution after HCT in vivo, Shultz, Ishikawa, and colleagues (28,29) + cell transfer. However, regardless of the source of HSC and the method for cell transplantation, humanized mice displayed suboptimal levels of lymphocyte reconstitution, and lacked or had low levels of Ag-specific cellular and humoral responses and overall anergy (30,31). Factors that may impact in the inefficient lymphatic development in HIS mice include the absence of human histocompatibility molecules and a poor humanized cytokine environment.…”

Section: Cd83mentioning

confidence: 99%

Dendritic Cell–Mediated Immune Humanization of Mice: Implications for Allogeneic and Xenogeneic Stem Cell Transplantation

Salguero

Daenthanasanmak

Münz

et al. 2014

The Journal of Immunology

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De novo regeneration of immunity is a major problem after allogeneic hematopoietic stem cell transplantation (HCT). HCT modeling in severely compromised immune-deficient animals transplanted with human stem cells is currently limited because of incomplete maturation of lymphocytes and scarce adaptive responses. Dendritic cells (DC) are pivotal for the organization of lymph nodes and activation of naive T and B cells. Human DC function after HCT could be augmented with adoptively transferred donor-derived DC. In this study, we demonstrate that adoptive transfer of long-lived human DC coexpressing high levels of human IFN-α, human GM-CSF, and a clinically relevant Ag (CMV pp65 protein) promoted human lymphatic remodeling in immune-deficient NOD.Rag1−/−.IL-2rγ−/− mice transplanted with human CD34+ cells. After immunization, draining lymph nodes became replenished with terminally differentiated human follicular Th cells, plasma B cells, and memory helper and cytotoxic T cells. Human Igs against pp65 were detectable in plasma, demonstrating IgG class-switch recombination. Human T cells recovered from mice showed functional reactivity against pp65. Adoptive immunotherapy with engineered DC provides a novel strategy for de novo immune reconstitution after human HCT and a practical and effective tool for studying human lymphatic regeneration in vivo in immune deficient xenograft hosts.

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Section: Cd83mentioning

confidence: 99%

Dendritic Cell–Mediated Immune Humanization of Mice: Implications for Allogeneic and Xenogeneic Stem Cell Transplantation

Salguero

Daenthanasanmak

Münz

et al. 2014

The Journal of Immunology

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“…Lepus et al 22 reported that CD34 1 cells from fetal liver were more efficient than those from cord blood or G-CSF-mobilized PB. In addition, Matsumura et al 23 reported that CD34 1 cells from cord blood were more effective than those from G-CSF-mobilized PB and BM.…”

Section: Introductionmentioning

confidence: 99%

Current advances in humanized mouse models

et al. 2012

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Humanized mouse models that have received human cells or tissue transplants are extremely useful in basic and applied human disease research. Highly immunodeficient mice, which do not reject xenografts and support cell and tissue differentiation and growth, are indispensable for generating additional appropriate models. Since the early 2000s, a series of immunodeficient mice appropriate for generating humanized mice has been successively developed by introducing the IL-2Rc null gene (e.g., NOD/SCID/cc null and Rag2 null cc null mice). These strains show not only a high rate of human cell engraftment, but also generate well-differentiated multilineage human hematopoietic cells after human hematopoietic stem cell (HSC) transplantation. These humanized mice facilitate the analysis of human hematology and immunology in vivo. However, human hematopoietic cells developed from HSCs are not always phenotypically and functionally identical to those in humans. More recently, a new series of immunodeficient mice compensates for these disadvantages. These mice were generated by genetically introducing human cytokine genes into NOD/SCID/cc null and Rag2 null cc null mice. In this review, we describe the current knowledge of human hematopoietic cells developed in these mice. Various human disease mouse models using these humanized mice are summarized.

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“…6 Transfer of human CD34 1 HSCs in these mice leads to multilineage hematopoiesis with variable levels of reconstitution depending on the strain and age of recipient mice and the source of donor HSCs. 7,8 Despite robust lymphoid reconstitution in most models, adaptive immune responses remain incomplete in both the CD34 1 HSC model as well as advanced models incorporating concurrently implanted The online version of this article contains a data supplement.…”

Section: Introductionmentioning

confidence: 99%

Fatal autoimmunity in mice reconstituted with human hematopoietic stem cells encoding defective FOXP3

Goettel

Biswas

Lexmond

et al. 2015

Blood

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• Improved adaptive immune responses in humanized mice lacking murine MHC II and expressing human HLADR1.• NOD.Prkdc H2-Ab1 2/2Tg(HLA-DR1) mice reconstituted with hematopoietic stem cells from an IPEX syndrome patient develop fatal autoimmunity.Mice reconstituted with a human immune system provide a tractable in vivo model to assess human immune cell function. To date, reconstitution of murine strains with human hematopoietic stem cells (HSCs) from patients with monogenic immune disorders have not been reported. One obstacle precluding the development of immune-disease specific "humanized" mice is that optimal adaptive immune responses in current strains have required implantation of autologous human thymic tissue. To address this issue, we developed a mouse strain that lacks murine major histocompatibility complex class II (MHC II) and instead expresses human leukocyte antigen DR1 (HLA-DR1). These mice displayed improved adaptive immune responses when reconstituted with human HSCs including enhanced T-cell reconstitution, delayed-type hypersensitivity responses, and class-switch recombination. Following immune reconstitution of this novel strain with HSCs from a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, associated with aberrant FOXP3 function, mice developed a lethal inflammatory disorder with multiorgan involvement and autoantibody production mimicking the pathology seen in affected humans. This humanized mouse model permits in vivo evaluation of immune responses associated with genetically altered HSCs, including primary immunodeficiencies, and should facilitate the study of human immune pathobiology and the development of targeted therapeutics. (Blood. 2015;125(25):3886-3895)

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Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/γc−/−, Balb/c-Rag1−/−γc−/−, and C.B-17-scid/bg immunodeficient mice

Cited by 108 publications

References 45 publications

Dendritic Cell–Mediated Immune Humanization of Mice: Implications for Allogeneic and Xenogeneic Stem Cell Transplantation

Dendritic Cell–Mediated Immune Humanization of Mice: Implications for Allogeneic and Xenogeneic Stem Cell Transplantation

Current advances in humanized mouse models

Fatal autoimmunity in mice reconstituted with human hematopoietic stem cells encoding defective FOXP3

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