A5044496329- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Virus-based gene therapy research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Asthma and respiratory diseases
- CRISPR and Genetic Engineering
- IL-33, ST2, and ILC Pathways
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer Research and Treatments
- Lung Cancer Treatments and Mutations
- Mesenchymal stem cell research
- Allergic Rhinitis and Sensitization
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Neuroendocrine Tumor Research Advances
- Sepsis Diagnosis and Treatment
- Medical Imaging and Pathology Studies
- Immune cells in cancer
- Neuroblastoma Research and Treatments
- Tracheal and airway disorders
- Cancer Cells and Metastasis
- Animal Genetics and Reproduction
Nihon University
2025
Central Institute for Experimental Animals
2015-2024
Niigata University
2005-2024
Ehime Medical Center
2017-2024
National Hospital Organization
2017-2023
Shonan Kamakura General Hospital
2015-2022
ORCID
2021
Osaka City University
2017
Juntendo University
2016
Ehime University
2006-2015
'Humanized mice' are anticipated to be a valuable tool for studying the human immune system, but reconstituted cells have not yet been well characterized. Here, we extensively investigated differentiation and functions of B T in supra-immunodeficient mouse strain, NOD/shi-scid/γcnull (NOG) with CD34+ hematopoietic stem obtained from umbilical cord blood. In these hu-HSC NOG mice, development was partially blocked, significant number B-cell progenitors accumulated spleen. The mature...
Abstract The development of animal models that mimic human allergic responses is crucial to study the pathophysiology disease and generate new therapeutic methodologies. Humanized mice reconstituted with immune systems are essential reactions in vivo expected be useful for studying allergies. However, application this technology allergies has been limited, largely because poor myeloid cells, especially granulocytes mast which responsible mediating diseases, conventional humanized mice. In...
Background. Several animal models for xenogenic (xeno) graft versus host disease (GVHD) have been developed in immunodeficient mice, such as C.B-17-scid and nonobese diabetes (NOD)/severe combined immunodeficiency (SCID), by human peripheral blood mononuclear cell (hPBMC) transplantation. However, these pose problems because they require sublethal total body irradiation of the mice a large number hPBMCs to induce GVHD, timing onset GVHD is also unstable. The aim this study establish improved...
Mounting evidence has demonstrated that NOD-Shi/scid/γc(null) (NOG) mice are one of the most suitable mouse strains for humanized technologies, in which various human cells or tissues can be engrafted without rejection and autonomously maintained. We have characterized analyzed features immune system reconstituted NOG by transplanting hematopoietic stem (hu-HSC). One problems quasi-immune these hu-HSC is quality responses not always sufficient, as lack IgG production response to antigen...
We generated a severe immunodeficient NOD/Shi-scid-IL-2Rγ(null) (NOG) mouse substrain expressing the transgenic human IL-2 gene (NOG-IL-2 Tg). Upon transfer of cord blood-derived hematopoietic stem cells (HSCs), CD3(-)CD56(high)CD16(+/-) developed unexpectedly, predominantly in NOG-IL-2 Tg (hu-HSC These expressed various NK receptors, including NKp30, NKp44, NKp46, NKG2D, and CD94, as well diverse set killer cell Ig-like receptor molecules at levels comparable to normal from peripheral...
We generated a novel mouse strain expressing transgenic human interleukin-15 (IL-15) using the severe immunodeficient NOD/Shi-scid-IL-2Rγ null (NOG) genetic background (NOG-IL-15 Tg). Human natural killer (NK) cells, purified from peripheral blood (hu-PB-NK) of normal healthy donors, proliferated when transferred into NOG-IL-15 Tg mice. In addition, cell number increased, and hu-PB-NK cells persisted for 3 months without signs xenogeneic graft versus host diseases (xGVHD). These in...
The tumor microenvironment contains unique immune cells, termed myeloid derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that suppress host anti-tumor immunity promote angiogenesis metastasis. Although these are considered a key target of cancer therapy, in vivo animal models allowing differentiation human immunosuppressive have yet to be established, hampering the development novel therapies. In this study, we established humanized transgenic (Tg) mouse strain,...
Graft-versus-host disease (GVHD) is a major complication of allogenic bone marrow transplantation and involves the infiltration donor CD4+ and/or CD8+ T cells into various organs recipient. The pathological role human in GVHD remains controversial. In this study, we established two novel xenogeneic (xeno)-GVHD models. Human or were purified from peripheral blood transplanted immunodeficient NOD/Shi-scid IL2rgnull (NOG) mice. did not induce symptoms conventional NOG However, immediately...
Neutrophil elastase plays a crucial role in the development of acute lung injury (ALI) patients with systemic inflammatory response syndrome (SIRS). The clinical efficacy neutrophil inhibitor, sivelestat, for ALI associated SIRS has not been convincingly demonstrated. aim this study was to determine if there are features condition that affect sivelestat.This retrospective 110 SIRS. Clinical information, including etiology ALI, number organs failing, scoring systems assessing severity...
Asthma is one of the most common immunological diseases and characterized by airway hyperresponsiveness (AHR), mucus overproduction, eosinophilia. Although mouse models have provided insight into mechanisms which type-2 cytokines induce asthmatic inflammation, differences between rodent human immune systems hamper efforts to improve understanding allergic diseases. In this study, we aim establish a preclinical animal model inflammation using humanized IL-3/GM-CSF or IL-3/GM-CSF/IL-5 Tg...
Primary human hepatocytes (PHHs) have been commonly used as the gold standard in many drug metabolism studies, regardless of having large inter-individual variation. These variations PHHs arise primarily from genetic polymorphisms, well donor health conditions and storage prior to cell processing. To equalize effects latter two factors, were transplanted quality-controlled mice providing hepatocyte proliferation niches, engrafted livers generated. Cells that harvested livers, call this...
Abstract Leukemia stem cells (LSCs) in chronic myeloid leukemia (CML) are quiescent, insensitive to BCR-ABL1 tyrosine kinase inhibitors (TKIs) and responsible for CML relapse. Therefore, eradicating quiescent LSCs is a major goal therapy. Here, using G 0 marker (G M), we narrow down as M- CD27- double positive among the conventional LSCs. Whole transcriptome analysis reveals NF-κB activation via inflammatory signals imatinib-insensitive Blocking by of interleukin-1 receptor-associated 1/4...
DNA hypomethylating agents (HMAs) are used for the treatment of myeloid malignancies, although their therapeutic effects have been unsatisfactory. Here we show that CRISPR-Cas9 screening reveals knockout topoisomerase 1-binding arginine/serine-rich protein (TOPORS), which encodes a ubiquitin/SUMO E3 ligase, augments efficacy HMAs on leukemic cells with little effect normal hematopoiesis, suggesting TOPORS is involved in resistance to HMAs. incorporated into and trap methyltransferase-1...
Osteopontin (OPN) is a multifunctional protein that plays important roles in cell growth, differentiation, migration and tissue fibrosis. In human idiopathic pulmonary fibrosis murine bleomycin-induced lung fibrosis, OPN upregulated type II alveolar epithelial cells (AEC II). However, the mechanism of induction AEC not fully understood. this study, we demonstrate molecular elucidate functions fibroblasts. Human adenocarcinoma (A549) mouse (MLE12), used as lines for vitro assays, (HPAEpiC)...