DOCSLIB.ORG

Humanized Mouse Models Fact Sheet

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

ALZET Research Application Humanized Mouse Models The nude mouse and severe combined immunodeficiency (SCID) mouse have ALZET Pump Highlights traditionally been used as recipients for human cells or tissues because they lack host immunity and easily accept heterologous cells. The introduction of • Small size for implantation • 9 pump models for mice the non-obese diabetic (NOD)/SCID mouse led to the development of highly • Continuous and controlled immunodeficient strains, able to engraft human cells and tissues more delivery of agents efficiently, which are more appropriate for generating humanized mouse • Minimize side effects and models. experimental variables • Convenient and cost- effective dosing method The humanized mouse – a mouse carrying functional human genes, cells, • Reduced animal handling tissues, and/or organs – is now a powerful research tool for the in vivo study of and stress • Delivery rates ranging from human biology and disease. Humanized mouse models enable a better 0.11 µl/hr to 8 µl/hr understanding of disease pathways and ultimately improve the translational • Delivery durations ranging value of preclinical studies. Various humanized mouse models have been from 1 day to 6 weeks developed for the study of infectious diseases, autoimmunity, transplantation, vaccine development, cancer immunotherapy, regenerative medicine, cell development, and more. Immunodeficient Strains* ALZET® Osmotic Pumps are used extensively with immunodeficient mice, and Nude Mouse hundreds of publications attest to their research value in these species. These SCID Mouse implantable infusion pumps offer a convenient alternative to repetitive NOD/SCID Mouse injections for continuous dosing of unrestrained lab animals. Their automatic NSG Mouse operation, small size and simple design make them suitable for chronic dosing NOG Mouse studies in humanized mouse models. No researcher intervention is required during infusion, and animal handling is kept to a minimum to reduce the risk of NRG Mouse infection and stress. Read on for research summaries describing the use of *See page 4 for complete ALZET pumps in humanized mouse models. Contact us for additional descriptions information at 800.692.2990 or [email protected]. DURECT CORPORATION | 10260 BUBB ROAD | CUPERTINO CA, 95014-4166 T: 408.367.4036 F: 408.865.1406 TOLL FREE 800.692.2990 WWW.ALZET.COM | [email protected] Use of ALZET Pumps in Humanized Mouse Models Suzuki et al. Generation of engraftable hematopoietic stem cells from induced pluripotent stem cells by way of teratoma formation. Molecular Therapy 2013;21(7):1424–1431 Purpose (1) Develop an in vivo differentiation system for the generation of engraftable hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) to facilitate hematopoiesis. (2) Investigate teratomas as a suitable microenvironment for the generation of engraftable HSCs with bone marrow (BM) niche migration potential. Mouse Model Transplantation of BM cells (hiPSC-derived HSCs) of teratoma-bearing mice into irradiated NOD/SCID or NOD/SCID/ JAK3null recipient mice. Role of ALZET Continuous, SC administration of the hematopoietic cytokines, stem cell factor (SCF) and thrombopoietin (TPO), over 2 weeks in teratoma-bearing mice to stimulate differentiation of iPSCs into HSCs. Key Findings • HSCs were successfully induced by injection of iPSCs into immunodeficient mice and reproducing the HSC niche by way of teratoma formation. Co-administration of OP9 stromal cells along with hematopoietic cytokines dramatically enhanced the induction efficiency. • HSCs derived from iPSCs showed self-renewal and multi-lineage differentiation capabilities. • iPSC-derived HSCs were shown to migrate from teratomas into the BM niche following IV injection into irradiated recipients, where they are capable of long-term reconstitution of the hematolymphopoietic system. • Established an in vivo differentiation system to generate fully functional, xenotransplantable HSCs from iPSCs through teratoma formation. Gang et al. Small-molecule inhibition of CBP/catenin interactions eliminates drug-resistant clones in acute lymphoblastic leukemia. Oncogene 2013:1-10 Purpose Evaluate the efficacy of ICG-001, a novel small-molecule inhibitor of Wnt/beta catenin signaling, with or without traditional chemotherapy with nilotinib (NTB) or VDL (vincristine, dexamethasone and L-asparaginase). Mouse Model Xenograft model of primary acute lymphoblastic leukemia (ALL) in NOD/SCID gamma (NSG) mice. Role of ALZET Model 1004 used for subcutaneous administration of ICG-001 for 28 days to ensure stable plasma dosing levels. Key Findings • ICG-001 treatment in combination with chemotherapy significantly prolonged survival of mice engrafted with primary ALL: a mean survival time (MST) of 100 days was seen in mice treated with ICG-001 plus chemotherapy, compared to 85 days MST for chemotherapy only-treated mice, 37.5 days MST for ICG-001 only treated mice, and 34 days MST for saline control-treated mice. • Selective inhibition of CBP/catenin signaling with ICG-001 prevents self-renewal of drug-resistant leukemia- initiating cells by forced differentiation, thereby sensitizing them to chemotherapy. • This approach represents a promising therapeutic strategy for specifically eradicating drug-resistant leukemia- initiating cells. Klug et al. Low-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell 2013;24:589–602. Purpose Evaluate the effect of low-dose irradiation (LDI) as adjuvant for improving the efficacy of adoptive T cell therapy or tumor vaccination on various xenograft tumor models. Mouse Model Human melanoma (MeWo) xenograft model in NOD/SCID gamma (NSG) mice and NOD/SCID mice for cancer immunotherapy; RIP1-Tag5 (RT5) pancreatic tumor xenograft model in NOD/SCID mice. Role of ALZET Model 2002 used for subcutaneous administration of the selective iNOS inhibitor 1400W over 2 weeks to evaluate the effect of iNOS inhibition on vascular normalization, activation, and T cell recruitment into RT5 tumors. Key Findings • iNOS inhibition by 1400W treatment eliminated NO secretion in irradiated and CD8TC-treated tumors and completely inhibited vascular cell adhesion protein-1 expression. • LDI programs the differentiation of iNOS+ M1 macrophages which induce CTL recruitment and killing within solid tumors by inducing endothelial activation and TH1 chemokine expression, as well as by suppressing the production of angiogenic, immunosuppressive, and tumor growth factors. • iNOS+ macrophages are required to mediate effector T cell recruitment into tumors for successful tumor immune rejection through an NO-dependent mechanism. • Adoptive transfer of iNOS-expressing macrophages is a promising strategy to improve the efficacy of cancer immunotherapy. DURECT CORPORATION | 10260 BUBB ROAD | CUPERTINO CA, 95014-4166 T: 408.367.4036 F: 408.865.1406 TOLL FREE 800.692.2990 WWW.ALZET.COM | [email protected] Use of ALZET Pumps in Humanized Mouse Models Krause et al. Differential regulation of myeloid leukemias by the bone marrow microenvironment. Nature Med 2013;19:1513–1517 Purpose Evaluate the effect of human parathyroid hormone (PTH) for modulation of the bone marrow microenvironment to eliminate persistent and drug resistant leukemia stem cells (LSC) in chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML). Mouse Model Xenograft model of chronic myelogenous leukemia in NOD/SCID IL-2 receptor γ deficient (NSG) mice. Role of ALZET 14-day ALZET pumps used for SC administration of human PTH (1–34) for 18 weeks (PTH treatment started 4 weeks prior to xenotransplantation and continued for 14 weeks thereafter, with pump replacement every two weeks). Key Findings • PTH treatment caused a 15-fold decrease in LSCs in wild type mice with CML-like myeloproliferative neoplasia and significantly reduced engraftment of primary human CML cells in NSG mice. • The beneficial effect of PTH in CML is mediated via suppressive effects of TGF-β. • Study suggests that targeting the hematopoietic microenvironment through PTH may render it hostile for CML cells, indicating that alteration of the tumor microenvironment is a potentially complementary approach to tumor cell-specific therapy. Chandramohan et al. Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors. Int J Cancer. 2013;132(10) Purpose Evaluate the intracranial efficacy of an anti-podoplanin immunotoxin (NZ-1-(scdsFv)-PE38KDEL) in the meduloblastoma tumor model. Mouse Model Intracranial meduloblastoma xenograft model in NOD/SCID gamma (NSG) mice. Role of ALZET Model 1003D used for administration (3 days) of an anti-podoplanin immunotoxin directly into the brain tumor site to bypass the blood-brain barrier. Key Findings • The podoplanin tumor antigen is overexpressed in several glioblastoma and medulloblastoma xenograft cells. • Recombinant immunotoxin was highly efficacious against CNS tumors expressing podoplanin, increasing survival by 41% in tumor bearing mice compared to controls. • Podoplanin is a suitable candidate for targeted therapy of malignant brain tumors. Examples of Humanized Mouse Models Available BLT humanized (hBLT) mouse PBMC humanized (hPBMC) mouse • Modification of the SCID-Hu model • NSG mice engrafted with human peripheral blood • NOD/SCID mice engrafted with human liver and thymus mononuclear cells (hPBMC) tissues, along with autologous CD34+ HSCs • Perfect for short-term experiments where T cell engraftment • Robust
Recommended publications
  • Antiretroviral Drug Metabolism in Humanized PXR-CAR-CYP3A- NOG Mice S

    Antiretroviral Drug Metabolism in Humanized PXR-CAR-CYP3A- NOG Mice S

    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/02/23/jpet.117.247288.DC1 1521-0103/365/2/272–280$35.00 https://doi.org/10.1124/jpet.117.247288 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 365:272–280, May 2018 Copyright ª 2018 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. Antiretroviral Drug Metabolism in Humanized PXR-CAR-CYP3A- NOG Mice s JoEllyn M. McMillan, Denise A. Cobb, Zhiyi Lin, Mary G. Banoub, Raghubendra S. Dagur, Amanda A. Branch Woods, Weimin Wang, Edward Makarov, Ted Kocher, Poonam S. Joshi, Rolen M. Quadros, Donald W. Harms, Samuel M. Cohen, Howard E. Gendelman, Channabasavaiah B. Gurumurthy, Santhi Gorantla, and Larisa Y. Poluektova Department of Pharmacology and Experimental Neuroscience (J.M.M., D.A.C., M.G.B., R.S.D., A.A.B.W., W.W., E.M., T.K., P.S. J., H.E.G., S.G., L.Y.P.), Developmental Neuroscience, Munroe Meyer Institute for Genetics and Rehabilitation (C.B.G.), Department of Pharmaceutical Sciences (Z.L.), Mouse Genome Engineering Core Facility, Vice Chancellor for Research Office Downloaded from (R.M.Q., D.W.H., C.B.G.), and Department of Pathology and Microbiology (S.M.C.), University of Nebraska Medical Center, Omaha, Nebraska Received December 18, 2017; accepted February 22, 2018 ABSTRACT jpet.aspetjournals.org Antiretroviral drug (ARV) metabolism is linked largely to hepatic studies we used nanoformulated atazanavir (nanoATV) with or cytochrome P450 activity.
  • Humanized Mouse Models for the Study of Hepatitis C and Host Interactions

    Humanized Mouse Models for the Study of Hepatitis C and Host Interactions

    cells Review Humanized Mouse Models for the Study of Hepatitis C and Host Interactions Kylie Su Mei Yong 1, Zhisheng Her 1 and Qingfeng Chen 1,2,3,* 1 Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Proteos, Singapore 138673, Singapore; [email protected] (K.S.M.Y.); [email protected] (Z.H.) 2 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore 3 Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China * Correspondence: [email protected]; Tel.: +65-6586-9873 Received: 15 May 2019; Accepted: 13 June 2019; Published: 17 June 2019 Abstract: Hepatitis C virus (HCV) infection is commonly attributed as a major cause of chronic hepatotropic diseases, such as, steatosis, cirrhosis and hepatocellular carcinoma. As HCV infects only humans and primates, its narrow host tropism hampers in vivo studies of HCV-mammalian host interactions and the development of effective therapeutics and vaccines. In this context, we will focus our discussion on humanized mice in HCV research. Here, these humanized mice are defined as animal models that encompass either only human hepatocytes or both human liver and immune cells. Aspects related to immunopathogenesis, anti-viral interventions, drug testing and perspectives of these models for future HCV research will be discussed. Keywords: humanized mice; hepatitis C virus; liver; hepatotropic disease; steatosis; cirrhosis; hepatocellular carcinoma 1. Introduction First identified in 1989, hepatitis C virus (HCV) is an enveloped, positive-sense, single-stranded ribonucleic acid (RNA) virus belonging to the genus Hepacivirus of family Flaviviridae [1,2].
  • Modeling HIV Infection and Therapies in Humanized Mice

    Modeling HIV Infection and Therapies in Humanized Mice

    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2012 Modeling HIV infection and therapies in humanized mice Nischang, Marc ; Gers-Huber, Gustavo ; Audigé, Annette ; Akkina, Ramesh ; Speck, Robert F Abstract: The human immunodeficiency virus (HIV) type-1 is a human-specific virus. The lack ofa widely available small-animal model has seriously hampered HIV research. In 2004, a new humanised mouse model was reported. It was based on the intrahepatic injection of human CD34+ cord blood cells into newborn, highly immunodeficient mice. These mice develop a lymphoid system of human origin and are highly susceptible to HIV infection and showed disseminated infection, persistent viraemia and characteristic helper CD4+ T-cell loss. Here, we will briefly review the various existing humanised mouse models and highlight their value to the study of HIV infection. DOI: https://doi.org/10.4414/smw.2012.13618 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-68798 Journal Article Published Version Originally published at: Nischang, Marc; Gers-Huber, Gustavo; Audigé, Annette; Akkina, Ramesh; Speck, Robert F (2012). Modeling HIV infection and therapies in humanized mice. Swiss Medical Weekly, 142:w13618. DOI: https://doi.org/10.4414/smw.2012.13618 Review article: Medical intelligence | Published 9 July 2012, doi:10.4414/smw.2012.13618 Cite this as: Swiss Med Wkly. 2012;142:w13618 Modelling HIV infection and therapies in humanised mice Marc Nischanga, Gustavo Gers-Hubera, Annette Audigé a, Ramesh Akkinab, Roberto F. Specka a Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Switzerland b Department of Microbiology, Immunology and Pathology, Colorado State University, Colorado, USA Summary somewhat permissive to HIV infection [1].
  • Monitoring HIV DNA and Cellular Activation Markers in HIV-Infected Humanized Mice Under Cart Mary-Aude Rochat, Erika Schlaepfer, Stefan P

    Monitoring HIV DNA and Cellular Activation Markers in HIV-Infected Humanized Mice Under Cart Mary-Aude Rochat, Erika Schlaepfer, Stefan P

    Rochat et al. Virology Journal (2018) 15:191 https://doi.org/10.1186/s12985-018-1101-9 SHORT REPORT Open Access Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART Mary-Aude Rochat, Erika Schlaepfer, Stefan P. Kuster, Duo Li, Annette Audige, Sandra Ivic, Audrey Fahrny and Roberto F. Speck* Abstract Background: The major obstacle to cure of HIV type-1 infection is the presence of the HIV reservoir, hidden from the immune system and insensitive to combined antiretroviral therapy (cART). Eradication approaches have been hindered by the difficulty for accurately monitoring its size in vivo, especially in the lymphoid organs. Humanized mouse models are a valuable tool for systematically assess the efficacy of therapeutic interventions in reducing the HIV reservoir. Nonetheless, persistence of the HIV reservoir over time, in the presence of cART, has yet to be analyzed in this in vivo model. Findings: We found that the proviral DNA as well as the total DNA were very stable in the spleen and mesenteric lymph node irrespective of the length of cART. Notably, the amount of proviral DNA was very similar in the spleen and lymph node. Furthermore, we observed a correlation between the percentage of splenic human CD4+ T-cells with total HIV DNA, between the number of human CD38 + CD8+ T-cells in the spleen with the amount of integrated HIV DNA, and eventually between the hCD4/hCD8 ratio in the spleen with integrated as well as total HIV DNA implying that the CD8+ T cells influence the size of the HIV reservoir.
  • Modeling EBV Infection and Pathogenesis in New-Generation Humanized Mice

    Modeling EBV Infection and Pathogenesis in New-Generation Humanized Mice

    OPEN Experimental & Molecular Medicine (2015) 47, e135; doi:10.1038/emm.2014.88 & 2015 KSBMB. All rights reserved 2092-6413/15 www.nature.com/emm REVIEW Modeling EBV infection and pathogenesis in new-generation humanized mice Shigeyoshi Fujiwara1,2, Ken-Ichi Imadome1 and Masami Takei2 The development of highly immunodeficient mouse strains has allowed the reconstitution of functional human immune system components in mice. New-generation humanized mice generated in this manner have been extensively used for modeling viral infections that are exclusively human tropic. Epstein–Barr virus (EBV)-infected humanized mice reproduce cardinal features of EBV-associated B-cell lymphoproliferative disease and EBV-associated hemophagocytic lymphohistiocytosis (HLH). Erosive arthritis morphologically resembling rheumatoid arthritis (RA) has also been recapitulated in these mice. Low-dose EBV infection of humanized mice results in asymptomatic, persistent infection. Innate immune responses involving natural killer cells, EBV-specific adaptive T-cell responses restricted by human major histocompatibility and EBV-specific antibody responses are also elicited in humanized mice. EBV-associated T-/natural killer cell lymphoproliferative disease, by contrast, can be reproduced in a distinct mouse xenograft model. In this review, recent findings on the recapitulation of human EBV infection and pathogenesis in these mouse models, as well as their application to preclinical studies of experimental anti-EBV therapies, are described. Experimental & Molecular Medicine (2015) 47, e135; doi:10.1038/emm.2014.88; published online 23 January 2015 ANIMAL MODELS OF EPSTEIN–BARR VIRUS INFECTION EBV belongs to the genus lymphocryptovirus (LCV) of the Humans are the only natural host of Epstein–Barr virus (EBV). γ-herpesvirus subfamily.
  • 15 22 January 2020

    15 22 January 2020

    Joint Pathology Center Veterinary Pathology Services WEDNESDAY SLIDE CONFERENCE 2019-2020 C o n f e r e n c e 15 22 January 2020 Dr. Cory Brayton, DVM, PhD, DACVP, DACLAM, Director, Phenotypic Core Associate Professor of Molecular and Comparative and Pathobiology Johns Hopkins School of Medicine Baltimore MD CASE I: 16N131-1 (JPC 4128009). Microscopic Description: In sections of brain, there was a severe inflammatory Signalment: 3.5mo old, female, NOD.Cg- infiltrate composed exclusively of mature scid tm1Wjl Prkdc Il2rg /SzJ (NOD-SCID- and degenerate neutrophils within the third gamma/NSG) mouse (Mus musculus) and lateral ventricles, extending into the History: This mouse was xenografted in the subjacent neuropil of the hippocampus and mammary fat pad at 6 weeks of age with cerebrum with associated fragmentation and tumor cells from a breast cancer patient. The rarefaction of the neuropil. Several colonies mouse presented moribund, hunched and of short rod-shaped bacteria with peripheral scruffy two months later, and was clearing were observed within areas of subsequently euthanized. necrosis. The meninges were expanded with a mild inflammatory infiltrate composed Gross Pathology: The xenograft tumor was predominantly of neutrophils. In sections of not observed at gross necropsy. The mouse lung, multiple arteries contained variably was in poor body condition, with marked sized accumulations of fibrin, neutrophils, depletion of external and internal adipose and fewer macrophages, some containing stores. The lungs were mottled dark red, and similar rod-shaped bacteria. The the spleen was dark red to black and smaller perivascular interstitium and alveolar walls than normal. The small intestine contained were multifocally thickened with few small amounts of mucous, and few fecal neutrophils and macrophages, some of pellets were present in the descending colon.
  • Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy

    Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy

    cancers Article Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy Wai Nam Liu 1, Shin Yie Fong 1, Wilson Wei Sheng Tan 1 , Sue Yee Tan 1, Min Liu 1, Jia Ying Cheng 1, Sherlly Lim 1, Lisda Suteja 2, Edwin Kunxiang Huang 3, Jerry Kok Yen Chan 3,4, Narayanan Gopalakrishna Iyer 2 , Joe Poh Sheng Yeong 1, Darren Wan-Teck Lim 1,2,* and Qingfeng Chen 1,5,* 1 Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore; [email protected] (W.N.L.); [email protected] (S.Y.F.); [email protected] (W.W.S.T.); [email protected] (S.Y.T.); [email protected] (M.L.); [email protected] (J.Y.C.); [email protected] (S.L.); [email protected] (J.P.S.Y.) 2 Division of Medical Oncology, National Cancer Centre, Singapore 169610, Singapore; [email protected] (L.S.); [email protected] (N.G.I.) 3 Department of Reproductive Medicine, KK Women’s and Children’s Hospital, Singapore 229899, Singapore; [email protected] (E.K.H.); [email protected] (J.K.Y.C.) 4 Experimental Fetal Medicine Group, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore 5 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore * Correspondence: [email protected] (D.W.-T.L.); [email protected] (Q.C.); Tel.: +65-6586-9873 (Q.C.) Received: 22 March 2020; Accepted: 17 April 2020; Published: 22 April 2020 Abstract: Immune checkpoint blockade (ICB) monotherapy shows early promise for the treatment of nasopharyngeal carcinoma (NPC) in patients.
  • Humanized Mouse Model Supports Development, Function, and Tissue Residency of Human Natural Killer Cells

    Humanized Mouse Model Supports Development, Function, and Tissue Residency of Human Natural Killer Cells

    Humanized mouse model supports development, function, and tissue residency of human natural killer cells Dietmar Herndler-Brandstettera,1, Liang Shana,1,2, Yi Yaob,3, Carmen Stechera, Valerie Plajera, Melanie Lietzenmayera, Till Strowiga,4, Marcel R. de Zoetea,5, Noah W. Palma, Jie Chena, Catherine A. Blishc, Davor Frletad, Cagan Gurerd, Lynn E. Macdonaldd, Andrew J. Murphyd, George D. Yancopoulosd, Ruth R. Montgomeryb, and Richard A. Flavella,e,6 aDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06519; bDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06519; cDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305; dRegeneron Pharmaceuticals Inc., Tarrytown, NY 10591; and eHoward Hughes Medical Institute, New Haven, CT 06519 Contributed by Richard A. Flavell, September 18, 2017 (sent for review March 30, 2017; reviewed by Hergen Spits and Wayne M. Yokoyama) Immunodeficient mice reconstituted with a human immune sys- acids identical between humans and mice, is interleukin 15 (IL- tem represent a promising tool for translational research as they 15). IL-15 is essential for the development and/or function of NK may allow modeling and therapy of human diseases in vivo. cells, memory CD8 T cells, CD8αα intraepithelial lymphocytes However, insufficient development and function of human natural (IELs), and tissue-resident NK cells (10, 11). In addition, phys- killer (NK) cells and T cell subsets limit the applicability of human- iological levels of IL-15 are essential for functional antitumor ized mice for studying cancer biology and therapy. Here, we de- responses of NK and T cells in cancer immunotherapy (12).
  • 370 1. Abstract 2. Introduction: Natural Killer Cells Kill

    370 1. Abstract 2. Introduction: Natural Killer Cells Kill

    [Frontiers in Bioscience, Landmark, 22, 370-384, January 1, 2017] Novel strategies to target cancer stem cells by NK cells; studies in humanized mice Anna K. Kozlowska1,3, Kawaljit Kaur1, Paytsar Topchyan1, Anahid Jewett1,2 1Division of Oral Biology and Oral Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, CA, USA, 2The Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA, USA, 3Department of Tumor Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland TABLE OF CONTENTS 1. Abstract 2. Introduction: Natural killer cells kill and differentiate cancer stem-like cells 3. Studies of NK cells in xenogeneic implantation of human cells into immunodeficient mouse strains 4. Use of immunodeficient mouse strains in the studies of cancer immunity 5. Humanized mice as preclinical models to study the complexity of human immune system interactions 6. Potential limitations of allogeneic tumor transplantation in humanized mice 7. Are NK cells in humanized mice of sufficient quantity and quality? 8. NK cell receptor downregulation as potential mechanism for the detection of low NK cell frequencies in vivo 9. Adoptive therapy with osteoclast-expanded NK cells eliminates cancer stem-like cells in humanized mice 10. Future of NK cell mediated immunotherapy 11. Acknowledgements 12. References 1. ABSTRACT We have previously shown, that following represent the first line of defense against virally infected selection, natural killer (NK) cells differentiate cancer stem- cells and transformed cells. However, decreased NK like cells (CSCs)/poorly differentiated tumors via secreted cell cytotoxicity in the tumor microenvironment and and membrane bound IFN-gamma and TNF-alpha, peripheral blood of cancer patients, as well as down- leading to prevention of tumor growth and remodeling modulation of CD16 receptors on the surface of NK cells, of the tumor microenvironment.
  • Induction of Functional Human Macrophages in Humanized Mice

    Induction of Functional Human Macrophages in Humanized Mice

    Induction of functional human macrophages in humanized mice Dissertation with the aim of achieving a doctoral degree at the Faculty of Mathematics, Informatics and Natural Sciences Department of Biology of the University of Hamburg Submitted by Jan Engelhardt Hamburg, 2016 Date of oral defense: November 4th, 2016 The following evaluators recommend the admission of the dissertation: Prof. Dr. med. Klaus Pantel Prof. Dr. Julia Kehr I hereby declare, on oath, that I have written the present dissertation by my own and have not used other than the acknowledged resources and aids. Munich, 09.11.2016 Signature Table of contents 1. Summary .................................................................................................................... 3 2. Introduction ............................................................................................................... 5 3. Materials ................................................................................................................... 15 4. Methods .................................................................................................................... 21 5. Results ...................................................................................................................... 36 5.1. Characterization of CD34-enriched fetal liver cells............................................................... 36 5.2. Characterization of lymphoid organs in HIS BRG mice ......................................................... 38 5.2.1. Peripheral blood .................................................................................................................
  • NOG Mice Transgenic − Using Human IL-3/GM-CSF Establishment

    NOG Mice Transgenic − Using Human IL-3/GM-CSF Establishment

    Establishment of a Human Allergy Model Using Human IL-3/GM-CSF−Transgenic NOG Mice This information is current as Ryoji Ito, Takeshi Takahashi, Ikumi Katano, Kenji Kawai, of September 26, 2021. Tsutomu Kamisako, Tomoyuki Ogura, Miyuki Ida-Tanaka, Hiroshi Suemizu, Satoshi Nunomura, Chisei Ra, Akio Mori, Sadakazu Aiso and Mamoru Ito J Immunol 2013; 191:2890-2899; Prepublished online 16 August 2013; Downloaded from doi: 10.4049/jimmunol.1203543 http://www.jimmunol.org/content/191/6/2890 Supplementary http://www.jimmunol.org/content/suppl/2013/08/20/jimmunol.120354 http://www.jimmunol.org/ Material 3.DC1 References This article cites 45 articles, 24 of which you can access for free at: http://www.jimmunol.org/content/191/6/2890.full#ref-list-1 Why The JI? Submit online. by guest on September 26, 2021 • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists,
  • Humanized Mouse Models: Using Human Cells to Conquer Disease

    Humanized Mouse Models: Using Human Cells to Conquer Disease

    Humanized Mouse Models: Using Human Cells to Conquer Disease Rodent models provide significant insights into basic biology and underlying circuitry. But research on infectious diseases, viruses, and pathogenesis has been limited because animal models rely on the rodent’s own immune system—a vastly different physiological system Inject than a human’s. Our immune system is vital for resisting disease, but many unanswered Human Mouse questions remain about how immunity works. Humanized mouse models stems cells are developed from mice that have disabled immune systems. As shown in Figure 1, when human cells from fetal tissue are inserted in these animals, mice acquire human biological immunity and responses. Humanized mouse models represent one of many ways fetal tissue contributes to life-saving research1, combining the value of animal models with the accuracy of human immune responses, humanized Mouse develops with human mice are poised to revolutionize research by offering a way for scientists immune cells = Humanized mouse to directly study the human immune system.2,3 Scientists continue to create different techniques to produce these mouse models; each model has strengths and weaknesses. As in all Figure 1: Development of Humanized fields of research, the model that is chosen depends on the research Mouse Models. Schematic illustrating the question and available resources. For a more in-depth look at the four overall experimental design used to establish humanized mouse models. primary ways scientists develop humanized mouse models, please refer to the table on p. 3. BREAKTHROUGHS AND DISCOVERY Humanized mice are a premier model for infectious disease research, serving as key pre- clinical tools for a wide variety of translational studies: Human Immunodeficiency Virus (HIV): As of 2017, about 36.9 million individuals across the globe are HIV positive, 1.8 million of them under 15 years old.