8,559 results match your criteria humanized mice

Interferon signaling suppresses the unfolded protein response and induces cell death in hepatocytes accumulating hepatitis B surface antigen.

PLoS Pathog 2021 May 12;17(5):e1009228. Epub 2021 May 12.

Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Virus infection, such as hepatitis B virus (HBV), occasionally causes endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is counteractive machinery to ER stress, and the failure of UPR to cope with ER stress results in cell death. Mechanisms that regulate the balance between ER stress and UPR are poorly understood. Read More

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Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7.

Leukemia 2021 May 11. Epub 2021 May 11.

Institute for Molecular Medicine, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.

Humanized mouse models have become increasingly valuable tools to study human hematopoiesis and infectious diseases. However, human T-cell differentiation remains inefficient. We generated mice expressing human interleukin-7 (IL-7), a critical growth and survival factor for T cells, under the control of murine IL-7 regulatory elements. Read More

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Genetically edited CD34 cells derived from human iPS cells in vivo but not in vitro engraft and differentiate into HIV-resistant cells.

Proc Natl Acad Sci U S A 2021 May;118(20)

Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, CA 94143-1270;

Genetic editing of induced pluripotent stem (iPS) cells represents a promising avenue for an HIV cure. However, certain challenges remain before bringing this approach to the clinic. Among them, in vivo engraftment of cells genetically edited in vitro needs to be achieved. Read More

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Infection of humanized mice with a novel phlebovirus presented pathogenic features of sever fever with thrombocytopenia syndrome.

PLoS Pathog 2021 May 11;17(5):e1009587. Epub 2021 May 11.

School of Life Sciences, Ningxia University, Yinchuan, P.R. China.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne emerging phlebovirus with high mortality rates of 6.0 to 30%. SFTSV infection is characterized by high fever, thrombocytopenia, leukopenia, hemorrhage and multiple organ failures. Read More

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Humanized Mouse Models for the Advancement of Innate Lymphoid Cell-Based Cancer Immunotherapies.

Front Immunol 2021 22;12:648580. Epub 2021 Apr 22.

Department of Otolaryngology-Head and Neck Surgery, Stanford Cancer Institute and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, United States.

Innate lymphoid cells (ILCs) are a branch of the immune system that consists of diverse circulating and tissue-resident cells, which carry out functions including homeostasis and antitumor immunity. The development and behavior of human natural killer (NK) cells and other ILCs in the context of cancer is still incompletely understood. Since NK cells and Group 1 and 2 ILCs are known to be important for mediating antitumor immune responses, a clearer understanding of these processes is critical for improving cancer treatments and understanding tumor immunology as a whole. Read More

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Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes.

PLoS Biol 2021 May 7;19(5):e3001209. Epub 2021 May 7.

MOE Key Laboratory of Protein Science & Collaborative Innovation Center of Biotherapy, School of Medicine, Tsinghua University, Beijing, China.

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) threatens global public health and economy unprecedentedly, requiring accelerating development of prophylactic and therapeutic interventions. Molecular understanding of neutralizing antibodies (NAbs) would greatly help advance the development of monoclonal antibody (mAb) therapy, as well as the design of next generation recombinant vaccines. Here, we applied H2L2 transgenic mice encoding the human immunoglobulin variable regions, together with a state-of-the-art antibody discovery platform to immunize and isolate NAbs. Read More

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Integrase-derived peptides together with CD24-targeted lentiviral particles inhibit the growth of CD24 expressing cancer cells.

Oncogene 2021 May 6. Epub 2021 May 6.

Health Promotion Center and Integrated Cancer Prevention Center, Sourasky Medical Center, Tel-Aviv, Israel.

The integration of viral DNA into the host genome is mediated by viral integrase, resulting in the accumulation of double-strand breaks. Integrase-derived peptides (INS and INR) increase the number of integration events, leading to escalated genomic instability that induces apoptosis. CD24 is a surface protein expressed mostly in cancer cells and is very rarely found in normal cells. Read More

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KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection.

Cell Rep 2021 May;35(5):109056

Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland. Electronic address:

Herpesvirus infections shape the human natural killer (NK) cell compartment. While Epstein-Barr virus (EBV) expands immature NKG2A NK cells, human cytomegalovirus (CMV) drives accumulation of adaptive NKG2C NK cells. Kaposi sarcoma-associated herpesvirus (KSHV) is a close relative of EBV, and both are associated with lymphomas, including primary effusion lymphoma (PEL), which nearly always harbors both viruses. Read More

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Combining Mobilizing Agents with Busulfan to Reduce Chemotherapy-Based Conditioning for Hematopoietic Stem Cell Transplantation.

Cells 2021 Apr 30;10(5). Epub 2021 Apr 30.

Department of Immunology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

In the context of hematopoietic stem cell (HSC) transplantation, conditioning with myelo- and immune-ablative agents is used to eradicate the patient's diseased cells, generate space in the marrow and suppress immune reactions prior to the infusion of donor HSCs. While conditioning is required for effective and long-lasting HSC engraftment, currently used regimens are also associated with short and long-term side effects on extramedullary tissues and even mortality. Particularly in patients with severe combined immunodeficiency (SCID), who are generally less than 1-year old at the time of transplantation and often suffer from existing comorbidities. Read More

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Antibody-mediated depletion of CCR10+ EphA3+ cells ameliorates fibrosis in IPF.

JCI Insight 2021 May 4. Epub 2021 May 4.

Division of Pulmonary and Critical Care, Cedars-Sinai Medical Center, Los Angeles, United States of America.

Idiopathic Pulmonary Fibrosis (IPF) is characterized by aberrant repair that diminishes lung function via mechanisms that remain poorly understood. C-C chemokine receptor (CCR10) and its ligand, CCL28, were both elevated in IPF compared with normal donors. CCR10 was highly expressed by various cells from IPF lungs, most notably stage-specific embryonic antigen (SSEA)-4+ mesenchymal progenitor cells (MPCs). Read More

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Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice.

Gut Microbes 2021 Jan-Dec;13(1):1-20

Laboratorio de Bacterias Lácticas y Probióticos, Departamento de Biotecnología de Alimentos, IATA-CSIC, Paterna, Spain.

Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α1,6-GlcNAc, lacto--biose (LNB) and galacto--biose on the fecal microbiota and host-microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased ( and ) or decreased ( and ) in all disaccharide-supplemented groups. Read More

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Sexual Dimorphism in Hepatocyte Xenograft Models.

Cell Transplant 2021 Jan-Dec;30:9636897211006132

Department of Gastroenterology and Hepatology, 6993Erasmus University Medical Center, Rotterdam, The Netherlands.

Humanized liver mouse models are crucial tools in liver research, specifically in the fields of liver cell biology, viral hepatitis and drug metabolism. The livers of these humanized mouse models are repopulated by 3-dimensional islands of fully functional primary human hepatocytes (PHH), which are notoriously difficult to maintain in vitro. As low efficiency and high cost hamper widespread use, optimization is of great importance. Read More

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Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: a comprehensive review.

Cancer Sci 2021 May 3. Epub 2021 May 3.

Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, P.R. China.

Immunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre-clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. Read More

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ApoE4 attenuates cortical neuronal activity in young behaving apoE4 rats.

Neurobiol Dis 2021 Apr 28;155:105373. Epub 2021 Apr 28.

Department of Neurobiology, The School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address:

The E4 allele of apolipoprotein E (apoE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). However, apoE4 may cause innate brain abnormalities before the appearance of AD-related neuropathology. Understanding these primary dysfunctions is vital for the early detection of AD and the development of therapeutic strategies. Read More

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A hierarchical dynamic model used for investigating feed efficiency and its relationship with hepatic gene expression in APOE*3-Leiden.CETP mice.

Physiol Rep 2021 Apr;9(8):e14832

Department of Experimental Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Background: Feed efficiency (FE) is an important trait for livestock and humans. While the livestock industry focuses on increasing FE, in the current obesogenic society it is more of interest to decrease FE. Hence, understanding mechanisms involved in the regulation of FE and particularly how it can be decreased would help tremendously in counteracting the obesity pandemic. Read More

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PD-1 Inhibition Enhances Blinatumomab Response in a UCB/PDX Model of Relapsed Pediatric B-Cell Acute Lymphoblastic Leukemia.

Front Oncol 2021 13;11:642466. Epub 2021 Apr 13.

Oncology, Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Immune therapies such as blinatumomab, CD19-directed bispecific CD3 T-cell Engager (BiTE), have resulted in significant improvements in outcomes for relapsed B-cell acute lymphoblastic leukemia (B-ALL). However, up to half of blinatumomab treated patients do not respond completely or relapse after therapy. As a result, there is a need to identify potential strategies to improve the efficacy of BiTE therapy. Read More

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Engineered adeno-associated virus 3 vector with reduced reactivity to serum antibodies.

Sci Rep 2021 Apr 29;11(1):9322. Epub 2021 Apr 29.

Division of Neurological Gene Therapy, Center for Open Innovation, Jichi Medical University, Tochigi, Japan.

The natural serotypes of adeno-associated virus (AAV) or their variants, such as AAV8 and AAV5, are commonly used as vectors in the clinical programs for liver-targeted gene therapy. While AAV8 vectors are not highly efficient at targeting primary human hepatocytes, AAV3 vectors have recently demonstrated remarkable efficiency at targeting both human and non-human primate hepatocytes. However, the presence of high levels of neutralizing antibodies (NAbs) impedes transduction into hepatocytes, representing a major obstacle to the clinical application of AAV3 vectors. Read More

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CD271+CD51+PALLADIN- human mesenchymal stromal cells possess enhanced ossicle-forming potential.

Stem Cells Dev 2021 Apr 30. Epub 2021 Apr 30.

Kumamoto University, 13205, Kumamoto, Japan, 860-8555;

Human mesenchymal stem/stromal cells (hMSCs), when engrafted into immunodeficient mice can form ectopic bone organs with hematopoietic stem cell supportive functions. However, the ability to do so, through a cartilage intermediate appears limited to 30% of donor bone marrow samples. Here, we characterize the heterogeneous nature of hMSCs and their ability to efficiently form humanized ossicles observed in "good donors" to correlate with the frequency and functionality of chondrocyte progenitors. Read More

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Animal Models of Hepatitis B Virus Infection-Success, Challenges, and Future Directions.

Viruses 2021 04 28;13(5). Epub 2021 Apr 28.

110 Lewis Thomas Laboratory, Department of Molecular Biology, Princeton University, Washington Road, Princeton, New Jersey, NJ 11 08544-101, USA.

Chronic hepatitis B virus (HBV) infection affects more than 250 million people worldwide, which greatly increases the risk for terminal liver diseases, such as liver cirrhosis and hepatocellular carcinoma (HCC). Even though current approved antiviral therapies, including pegylated type I interferon (IFN) and nucleos(t)ide analogs, can effectively suppress viremia, HBV infection is rarely cured. Since HBV exhibits a narrow species tropism and robustly infects only humans and higher primates, progress in HBV research and preclinical testing of antiviral drugs has been hampered by the scarcity of suitable animal models. Read More

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Perspectives on Non-BLT Humanized Mouse Models for Studying HIV Pathogenesis and Therapy.

Viruses 2021 Apr 28;13(5). Epub 2021 Apr 28.

Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.

A variety of humanized mice, which are reconstituted only with human hematopoietic stem cells (HSC) or with fetal thymus and HSCs, have been developed and widely utilized as in vivo animal models of HIV-1 infection. The models represent some aspects of HIV-mediated pathogenesis in humans and are useful for the evaluation of therapeutic regimens. However, there are several limitations in these models, including their incomplete immune responses and poor distribution of human cells to the secondary lymphoid tissues. Read More

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Rifaximin as a Potential Treatment for IgA Nephropathy in a Humanized Mice Model.

J Pers Med 2021 Apr 16;11(4). Epub 2021 Apr 16.

INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France.

IgA Nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by the mesangial deposition of abnormally glycosylated IgA1 (Gd-IgA). The production of Gd-IgA occurs in mucose-associated lymphoid tissue (MALT). The microbiota plays a role in MALT modulation. Read More

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Human Somatostatin SST Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization.

Int J Mol Sci 2021 Apr 4;22(7). Epub 2021 Apr 4.

Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School & Centre for Neuroscience, H-7624 Pécs, Hungary.

Somatostatin receptor subtype 4 (SST) has been shown to mediate analgesic, antidepressant and anti-inflammatory functions without endocrine actions; therefore, it is proposed to be a novel target for drug development. To overcome the species differences of SST receptor expression and function between humans and mice, we generated an SST humanized mouse line to serve as a translational animal model for preclinical research. A transposon vector containing the and reporter gene construct driven by the regulatory elements were created. Read More

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Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections.

Immunity 2021 Apr 22. Epub 2021 Apr 22.

Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.

A cardinal feature of COVID-19 is lung inflammation and respiratory failure. In a prospective multi-country cohort of COVID-19 patients, we found that increased Notch4 expression on circulating regulatory T (Treg) cells was associated with disease severity, predicted mortality, and declined upon recovery. Deletion of Notch4 in Treg cells or therapy with anti-Notch4 antibodies in conventional and humanized mice normalized the dysregulated innate immunity and rescued disease morbidity and mortality induced by a synthetic analog of viral RNA or by influenza H1N1 virus. Read More

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Genome-Wide B Cell, CD4, and CD8 T Cell Epitopes That Are Highly Conserved between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Targets for Preemptive Pan-Coronavirus Vaccines.

J Immunol 2021 Apr 28. Epub 2021 Apr 28.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA;

Over the last two decades, there have been three deadly human outbreaks of coronaviruses (CoVs) caused by SARS-CoV, MERS-CoV, and SARS-CoV-2, which has caused the current COVID-19 global pandemic. All three deadly CoVs originated from bats and transmitted to humans via various intermediate animal reservoirs. It remains highly possible that other global COVID pandemics will emerge in the coming years caused by yet another spillover of a bat-derived SARS-like coronavirus (SL-CoV) into humans. Read More

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Understanding hepatitis B virus dynamics and the antiviral effect of interferon-α treatment in humanized chimeric mice.

J Virol 2021 Apr 28. Epub 2021 Apr 28.

The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA

Whereas the mode of action of lamivudine (LAM) against hepatitis B virus (HBV) is well established, the inhibition mechanism(s) of interferon-α are less completely defined. To advance our understanding, we mathematically modelled HBV kinetics during 14-day pegylated interferon-α-2a (pegIFN), LAM or pegIFN+LAM treatment of 39 chronically HBV-infected humanized uPA/SCID chimeric mice. Serum HBV DNA and intracellular HBV DNA were measured frequently. Read More

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Distinct Repopulation Activity in Hu-Mice Between CB- and LPB- CD34 Cells by Enrichment of Transcription Factors.

Int J Stem Cells 2021 Apr 30. Epub 2021 Apr 30.

Department of Biomedical Science, CHA University, Seongnam, Korea.

Background And Objectives: Human CD34 hematopoietic stem cells can reconstitute the human hematopoietic system when transplanted into immunocompromised mice after irradiation. Human leukapheresis peripheral blood (LPB)- and cord blood (CB)-derived CD34 cells have a similar capacity to reconstitute myeloid lineage cells in a humanized mice (hu-mice) model. However, potent stem cells, such as CB-CD34 cells, efficiently reconstitute the lymphoid system in vivo compared to LPB-CD34 cells. Read More

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Mixed xenogeneic porcine chimerism tolerizes human anti-pig natural antibody-producing cells in a humanized mouse model.

Xenotransplantation 2021 Apr 26:e12691. Epub 2021 Apr 26.

Department of Medicine, Columbia Center for Translational Immunology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Background: A major obstacle to the success of organ transplantation from pigs to humans, necessitated by the shortage of human organs, is robust humoral immune rejection by pig-reactive human antibodies. Mixed xenogeneic hematopoietic chimerism induces xenoreactive B cell tolerance in rodents, but whether mixed pig/human chimerism could induce tolerance of human B cells to pig xenoantigens is unknown.

Methods: We investigated this question using a humanized mouse model in which durable mixed (pig-human) xenogeneic chimerism can be established. Read More

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Human-Specific Neuropeptide S Receptor Variants Regulate Fear Extinction in the Basal Amygdala of Male and Female Mice Depending on Threat Salience.

Biol Psychiatry 2021 Mar 3. Epub 2021 Mar 3.

Institute of Physiology I, Westfälische Wilhelms-Universität, Münster, Germany. Electronic address:

Background: A nonsynonymous single nucleotide polymorphism in the neuropeptide S receptor 1 (NPSR1) gene (rs324981) results in isoleucine-to-asparagine substitution at amino acid 107. In humans, the ancestral variant (NPSR1 I107) is associated with increased anxiety sensitivity and risk of panic disorder, while the human-specific variant (NPSR1 N107) is considered protective against excessive anxiety. In rodents, neurobiological constituents of the NPS system have been analyzed in detail and their anxiolytic-like effects have been endorsed. Read More

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An optimized protocol for patient-derived xenograft in humanized mice to evaluate the role of IL-34 in immunotherapeutic resistance.

STAR Protoc 2021 Jun 8;2(2):100460. Epub 2021 Apr 8.

Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo 060-0815, Japan.

Previously, we identified a therapy-resistant role of IL-34 in an immune checkpoint blockade in murine models. To investigate whether a similar mechanism is applicable in human tumors as well, we used this protocol for the selection of IL-34-neutralizing antibody and transplanting human tumor tissue expressing both IL-34 and PD-L1 as a patient-derived xenograft in immunologically humanized mice. This model helps to determine the effect of IL-34 neutralization along with the immune checkpoint blockade in human tumors. Read More

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VEGFR-1/Flt-1 inhibition increases angiogenesis and improves muscle function in a mouse model of Duchenne muscular dystrophy.

Mol Ther Methods Clin Dev 2021 Jun 23;21:369-381. Epub 2021 Mar 23.

Shire Human Genetic Therapies, a Takeda company, Lexington, MA, USA.

Duchenne muscular dystrophy is characterized by structural degeneration of muscle, which is exacerbated by localized functional ischemia due to loss of nitric oxide synthase-induced vasodilation. Treatment strategies aimed at increasing vascular perfusion have been proposed. Toward this end, we have developed monoclonal antibodies (mAbs) that bind to the vascular endothelial growth factor (VEGF) receptor VEGFR-1 (Flt-1) and its soluble splice variant isoform (sFlt-1) leading to increased levels of free VEGF and proangiogenic signaling. Read More

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