Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγnull mice is enhanced by transgenic expression of membrane-bound human SCF

Brehm, Michael A.; Racki, Waldemar J.; Leif, Jean; Burzenski, Lisa M.; Hosur, Vishnu; Wetmore, Amber; Gott, Bruce; Herlihy, M.; Ignotz, Ronald A.; Dunn, Raymond M.; Shultz, Leonard D.; Greiner, Dale L.

doi:10.1182/blood-2011-05-353243

Cited by 79 publications

(75 citation statements)

References 46 publications

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“…In a transgenic NSG model that expressed membrane-bound human stem cell factor, human myeloid cell engraftment is increased in both irradiated and nonirradiated hosts. 27,30 Our levels of granulomonocytic hematopoiesis are comparable to those found in models of NSG mice in which there is no irradiation for preconditioning. 27 However, because ACK2 increases the rate of chimerism, this strategy can be used as an adjunct to improve the efficiency of in utero transplantation.…”

Section: Fetal Host Conditioning Increases Engraftment Ratesupporting

confidence: 76%

“…We found higher percentage of T-cell engraftment than typically noted in adult transplanted NSG mice, which may reflect homeostatic proliferation of T cells, as our CD34 1 human samples were not completely pure and did contain a percentage of human T cells (3% to 17%). Earlier transplantation of human cells into NSG mice results in higher percentage of T cells when compared with adult transplantation, 27 which may be taking place within our model. Although chronic graft-versus-host disease (GVHD) has been implicated in high T-cell numbers in NSG mice that receive human CD34 1 cells, 28 our mice showed no physical evidence of GVHD at 24 weeks.…”

Section: Foxp3mentioning

confidence: 91%

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Systemic multilineage engraftment in mice after in utero transplantation with human hematopoietic stem cells

et al. 2018

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Section: Fetal Host Conditioning Increases Engraftment Ratesupporting

confidence: 76%

Section: Foxp3mentioning

confidence: 91%

Systemic multilineage engraftment in mice after in utero transplantation with human hematopoietic stem cells

et al. 2018

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“…42 Moreover, mice that express membrane-bound human SCF rejected HLA-mismatched human skin grafts. 41 These observations demonstrate that next-generation humanized mouse models support the development of functional human immune cells in vivo. For more detailed information on human immune responses in humanized mice, we refer to the respective review articles.…”

Section: Mistrg Mice Alsomentioning

confidence: 82%

“…40 Similarly, the transgenic expression of cytokine-encoding genes under the control of a strong constitutive promoter provides support for human hematopoietic cell development. [41][42][43][44] However, these approaches all result in the expression of systemic supraphysiological concentrations of human cytokines. In the case of transgenic mice expressing human IL-3, GM-CSF and stem cell factor (SCF) this induces the mobilization of HSPC and limits long-term engraftment.…”

Section: Cytokine Support For Human Hematopoietic Development and Immmentioning

confidence: 99%

Humanized hemato-lymphoid system mice

et al. 2015

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O ver the last decades, incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system, have been developed and now represent an important research tool in the field. The most significant contributions made by means of humanized mice are the identification of normal and leukemic hematopoietic stem cells, the characterization of the human hematopoietic hierarchy, and their use as preclinical therapy models for malignant hematopoietic disorders. Successful xenotransplantation depends on three major factors: tolerance by the mouse host, correct spatial location, and appropriately cross-reactive support and interaction factors such as cytokines and major histocompatibility complex molecules. Each of these can be modified. Experimental approaches include the genetic modification of mice to faithfully express human support factors as non-cross-reactive cytokines, to create free niche space, the co-transplantation of human mesenchymal stem cells, the implantation of humanized ossicles or other stroma, and the implantation of human thymic tissue. Besides the source of hematopoietic cells, the conditioning regimen and the route of transplantation also significantly affect human hematopoietic development in vivo. We review here the achievements, most recent developments, and the remaining challenges in the generation of pre-clinicallypredictive systems for human hematology and immunology, closely resembling the human situation in a xenogeneic mouse environment. Humanized hemato-lymphoid system mice

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“…The generation of mice with gene defects that prevent formation of T and B cells (scid or rag mutations) and natural killer cells (through IL-2 receptor γ chain deficiency) resulted in models that sustain meaningful numbers of human blood cells (Ito et al, 2002;Traggiai et al, 2004), and these models are continuously being improved (Brehm et al, 2012;Strowig and Flavell, 2012). The individual techniques have all been described (see Fig.…”

Section: What Are Stem Cells and How Can They Be Generated In Vitro?mentioning

confidence: 99%

Stem cell-derived cell cultures and organoids for protozoan parasite propagation and studying host–parasite interaction

Klotz

Aebischer

Seeber

2012

International Journal of Medical Microbiology

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SummaryPossibilities to study the biology of human protozoan parasites and their interaction with the host remain severely limited, either because of non-existent or inappropriate animal models or because parasites cannot even be cultured in vitro due to strict human-host specificity or physiology. Here we discuss the prospects of using induced pluripotent stem cell (iPSC)-derived culture systems including organoids as a strategy to address many of these experimental bottlenecks. iPSCs already allow the generation of differentiated cell cultures for many human organs, and these cells and derivatives are amenable to reverse genetics in combination with advanced tools for genetic manipulation. We present examples of blood, neuron, liver, and intestine-dwelling protozoa, i.e. Plasmodium falciparum, Toxoplasma gondii and Giardia duodenalis, where iPSCs or organoids would allow addressing questions of cell and developmental biology, immunology, and pharmacology in unprecedented ways. Starting points and resources for iPSC experimentation are briefly discussed.

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Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγnull mice is enhanced by transgenic expression of membrane-bound human SCF

Cited by 79 publications

References 46 publications

Systemic multilineage engraftment in mice after in utero transplantation with human hematopoietic stem cells

Systemic multilineage engraftment in mice after in utero transplantation with human hematopoietic stem cells

Humanized hemato-lymphoid system mice

Stem cell-derived cell cultures and organoids for protozoan parasite propagation and studying host–parasite interaction

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