Topic
Humanized mouse
About: Humanized mouse is a research topic. Over the lifetime, 1375 publications have been published within this topic receiving 42373 citations.
Papers published on a yearly basis
Papers
TL;DR: NOD-scid IL2Rγnull mice engrafted with human mobilized blood stem cells provide a new in vivo long-lived model of robust multilineage human HSC engraftment.
Abstract: Ethical considerations constrain the in vivo study of human hemopoietic stem cells (HSC). To overcome this limitation, small animal models of human HSC engraftment have been used. We report the development and characterization of a new genetic stock of IL-2R common gamma-chain deficient NOD/LtSz-scid (NOD-scid IL2Rgamma(null)) mice and document their ability to support human mobilized blood HSC engraftment and multilineage differentiation. NOD-scid IL2Rgamma(null) mice are deficient in mature lymphocytes and NK cells, survive beyond 16 mo of age, and even after sublethal irradiation resist lymphoma development. Engraftment of NOD-scid IL2Rgamma(null) mice with human HSC generate 6-fold higher percentages of human CD45(+) cells in host bone marrow than with similarly treated NOD-scid mice. These human cells include B cells, NK cells, myeloid cells, plasmacytoid dendritic cells, and HSC. Spleens from engrafted NOD-scid IL2Rgamma(null) mice contain human Ig(+) B cells and lower numbers of human CD3(+) T cells. Coadministration of human Fc-IL7 fusion protein results in high percentages of human CD4(+)CD8(+) thymocytes as well human CD4(+)CD8(-) and CD4(-)CD8(+) peripheral blood and splenic T cells. De novo human T cell development in NOD-scid IL2Rgamma(null) mice was validated by 1) high levels of TCR excision circles, 2) complex TCRbeta repertoire diversity, and 3) proliferative responses to PHA and streptococcal superantigen, streptococcal pyrogenic exotoxin. Thus, NOD-scid IL2Rgamma(null) mice engrafted with human mobilized blood stem cells provide a new in vivo long-lived model of robust multilineage human HSC engraftment.
1,797 citations
TL;DR: It is suggested that multiple immunological dysfunctions, including cytokine production capability, in addition to functional incompetence of T, B, and NK cells, may lead to the high engraftment levels of xenograft in NOD/SCID/gamma(c)(null) mice.
1,516 citations
TL;DR: This Review discusses the development of these new generations of humanized mice, how they will facilitate translational research in several biomedical disciplines and approaches to overcome the remaining limitations of these models.
Abstract: The culmination of decades of research on humanized mice is leading to advances in our understanding of human haematopoiesis, innate and adaptive immunity, autoimmunity, infectious diseases, cancer biology and regenerative medicine. In this Review, we discuss the development of these new generations of humanized mice, how they will facilitate translational research in several biomedical disciplines and approaches to overcome the remaining limitations of these models.
1,348 citations
TL;DR: It is found that a chimeric adenoviral vector overcame the inherent resistance of primary human macrophages to genetic manipulation and imparted a sustained pro-inflammatory (M1) phenotype in humanized mice.
Abstract: Chimeric antigen receptor (CAR) T cell therapy has shown promise in hematologic malignancies, but its application to solid tumors has been challenging1–4. Given the unique effector functions of macrophages and their capacity to penetrate tumors5, we genetically engineered human macrophages with CARs to direct their phagocytic activity against tumors. We found that a chimeric adenoviral vector overcame the inherent resistance of primary human macrophages to genetic manipulation and imparted a sustained pro-inflammatory (M1) phenotype. CAR macrophages (CAR-Ms) demonstrated antigen-specific phagocytosis and tumor clearance in vitro. In two solid tumor xenograft mouse models, a single infusion of human CAR-Ms decreased tumor burden and prolonged overall survival. Characterization of CAR-M activity showed that CAR-Ms expressed pro-inflammatory cytokines and chemokines, converted bystander M2 macrophages to M1, upregulated antigen presentation machinery, recruited and presented antigen to T cells and resisted the effects of immunosuppressive cytokines. In humanized mouse models, CAR-Ms were further shown to induce a pro-inflammatory tumor microenvironment and boost anti-tumor T cell activity. Primary macrophages engineered to express chimeric antigen receptors have anti-tumor activity in humanized mice.
1,031 citations
TL;DR: This Review discusses recent advances in the development and utilization of humanized mice, the lessons learnt, the remaining challenges and the promise of using humanization mice for the in vivo study of human immunology.
Abstract: Significant advances in our understanding of the in vivo functions of human cells and tissues and the human immune system have resulted from the development of 'humanized' mouse strains that are based on severely immunodeficient mice with mutations in the interleukin-2 receptor common γ-chain locus. These mouse strains support the engraftment of a functional human immune system and permit detailed analyses of human immune biology, development and functions. In this Review, we discuss recent advances in the development and utilization of humanized mice, the lessons learnt, the remaining challenges and the promise of using humanized mice for the in vivo study of human immunology.
949 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 63 |
| 2024 | 103 |
| 2023 | 153 |
| 2022 | 170 |
| 2021 | 174 |
| 2020 | 152 |