Humanised mouse models for haematopoiesis and infectious diseases

Lysenko, Veronika; McHugh, Donal; Behrmann, Lena; Rochat, Mary-Aude; Wilk, C. Matthias; Kovtonyuk, Larisa V.; Bourquin, Jean‐Pierre; Münz, Christian; Manz, Markus G.; Speck, Roberto F.; Theocharides, Alexandre

doi:10.4414/smw.2017.14516

Cited by 6 publications

(6 citation statements)

References 178 publications

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“…Humanized mice have the ability to recapitulate certain aspects of the human immune system in vivo. However, a number of limitations in immune function should be mentioned at this point, which may preclude direct transfer of these results to human infections (reviewed in reference 25 ). Importantly, reconstituted human immune system components show similarities to cord blood immune cells.…”

Section: Discussionmentioning

confidence: 99%

“…Although direct interactions between HIV-1 and B cells have been reported several decades ago (22,23), there are, to our knowledge, no reports of HIV-1 replication in B cells in vivo or experimental coinfection of HIV-1 with EBV in vivo, as reviewed in reference 24. In this study, we aimed to characterize the influence of EBV infection on HIV-1 susceptibility and possible HIV-1 integration in EBV-transformed B cells for lentiviral reservoir generation, as well as its influence on viral and host gene transcription in comparison to CD4 + T cells in vitro. Humanized mice have been successfully used to separately investigate HIV-1 and EBV infection, pathogenesis, and immune control, and we and others could recapitulate the protective value of CD4 + or CD8 + T cells against EBV-mediated lymphoproliferation in these models (25,26,27,28). Here, we modelled and investigated the effect of HIV-1 on EBV-specific immune control via coinfection of humanized mice.…”

Section: Introductionmentioning

confidence: 99%

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EBV renders B cells susceptible to HIV-1 in humanized mice

et al. 2020

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HIV and EBV are human pathogens that cause a considerable burden to worldwide health. In combination, these viruses are linked to AIDS-associated lymphomas. We found that EBV, which transforms B cells, renders them susceptible to HIV-1 infection in a CXCR4 and CD4-dependent manner in vitro and that CXCR4-tropic HIV-1 integrates into the genome of these B cells with the same molecular profile as in autologous CD4+ T cells. In addition, we established a humanized mouse model to investigate the in vivo interactions of EBV and HIV-1 upon coinfection. The respective mice that reconstitute human immune system components upon transplantation with CD34+ human hematopoietic progenitor cells could recapitulate aspects of EBV and HIV immunobiology observed in dual-infected patients. Upon coinfection of humanized mice, EBV/HIV dual-infected B cells could be detected, but were susceptible to CD8+ T-cell–mediated immune control.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

EBV renders B cells susceptible to HIV-1 in humanized mice

et al. 2020

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“…However, several signaling components of the mouse are incongruent with those of humans. In particular AML remains one of the hematologic malignancies with low engraftment performance in NSG mice ( 69 ). As a result, several attempts have been made to customize the bone marrow microenvironment to enable myeloid infiltration.…”

Section: Animal Models For Aml Niche Analysismentioning

confidence: 99%

Acute Myeloid Leukemia and the Bone Marrow Niche—Take a Closer Look

2018

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The bone marrow is the home of hematopoiesis and is therefore a hotspot for the development of hematopoietic diseases. Complex interactions between the bone marrow microenvironment and hematopoietic stem cells must find a balance between proliferation, differentiation and homeostasis of the stem cell compartment. Changes in this tightly regulated network can provoke malignant transformation, leading to hematopoietic diseases. Here we focus on acute myeloid leukemia (AML), since this is the most frequent acute leukemia in adulthood with very poor overall survival rates and where relapse after chemotherapy continues to be a major challenge, driving demand for new therapeutic strategies. Current research is focusing on the identification of specific interactions between leukemic blasts and their niche components, which may be exploited as novel treatment targets along with induction chemotherapy. Significant progress has been gained over the last few years in the field of high-resolution imaging. Confocal ex vivo and intravital microscopy have revealed a detailed map of bone marrow structures and components; as well as identifying numerous alterations in the stem cell niche that correspond to disease progression. However, the underlying mechanisms are still not completely understood and due to the complexity, their elucidation remains a challenging. This review discusses the constitution of the AML niche in the bone marrow, the improvement in visualization of the complex three-dimensional niche structures and points out new therapeutic strategies to increase the overall survival of AML patients.

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“…The study of malignant haematopoietic disorders, leading to the identification of leukaemia stem cells and leukaemia-initiating cells 42 , is another important application of humanized mouse models. Initial studies in this area [43][44][45] have been instrumental to advance our understanding of the mechanisms underlying the development of and explore therapeutic strategies for human leukaemias [46][47][48][49] .…”

Section: Utility Of Humanized Mouse Modelsmentioning

confidence: 99%

Humanized mouse models for immuno-oncology research

et al. 2023

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Immunotherapy has emerged as a promising treatment paradigm for many malignancies and is transforming the drug development landscape. Although immunotherapeutic agents have demonstrated clinical efficacy, they are associated with variable clinical responses, and substantial gaps remain in our understanding of their mechanisms of action and specific biomarkers of response. Currently, the number of preclinical models that faithfully recapitulate interactions between the human immune system and tumours and enable evaluation of human-specific immunotherapies in vivo is limited. Humanized mice, a term that refers to immunodeficient mice co-engrafted with human tumours and immune components, provide several advantages for immuno-oncology research. In this Review, we discuss the benefits and challenges of the currently available humanized mice, including specific interactions between engrafted human tumours and immune components, the development and survival of human innate immune populations in these mice, and approaches to study mice engrafted with matched patient tumours and immune cells. We highlight the latest advances in the generation of humanized mouse models, with the aim of providing a guide for their application to immuno-oncology studies with potential for clinical translation.• Next-generation humanized mouse models are being generated to better recapitulate the development of human innate and adaptive immunity. The development and use of novel humanized mouse platforms will accelerate the discovery and testing of new immunotherapies for patients with cancer.Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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Humanised mouse models for haematopoiesis and infectious diseases

Cited by 6 publications

References 178 publications

EBV renders B cells susceptible to HIV-1 in humanized mice

EBV renders B cells susceptible to HIV-1 in humanized mice

Acute Myeloid Leukemia and the Bone Marrow Niche—Take a Closer Look

Humanized mouse models for immuno-oncology research

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