Hematopoietic stem cells. Presentation outline: Embryonic und adult tissue stem cells. Hematopoietic stem cells
|
|
- Daniel Burke
- 6 years ago
- Views:
Transcription
1 SCA1-Height R Hematopoietic stem Totipotent Stem Cell Zygote Embryonic und adult tissue stem Pluripotent Stem Cell Embryonic Stem (ES) Cells T-CELL LYMPHOID STEM CELL B-CELL PLASMA CELL Multipotent Tissue Stem Cells BFU-E ERYTHROCYTE Aleksandra Wodnar-Filipowicz Department of Biomedicine University Hospital Basel Switzerland ESH-EBMT Targu Muresh Neural Muscle Liver Epidermis Retina Hematopoietic Cancer Stem Cells MYELOID STEM CELL CFU-GM CFU-Eo CFU-Baso CFU-Meg NEUTROPHIL MONOCYTE MACROPHAGE EOSINOPHIL BASOPHIL PLATELETS 2 MEGAKARYOCYTE Hematopoietic stem Presentation outline: 1. Bone marrow hematopoietic stem 2. Bone marrow stem cell 3. Leukemia stem 4. Embryonic/pluripotent stem! Therapeutic concepts c-kit c-kit Mouse Phenotype Lin - LSK sca % ckit + of BM tie2 + flk2 - CXCR4 + ABCG2 + SLAM-Rs: CD150 + CD244 - CD48 - TLR4 + BL6 % LSK : 0.007% sca-1 Human Phenotype Lin - CD34 + CD38 - ckit + flk2 - CD133 + CXCR4 + ABCG2 + Side population (SP) (ABCG2 + transporter) Hoechst blue Hoechst Blue 0.2% SP Hoechst Far Red Hoechst far red CD34 + CD38-0.1% of BM 3 4 Human hematopoietic stem In vitro CFU assays Function In vivo transplantation: xenografts in immunologically permissive mouse strains (e.g...nod/scid; NOD/SCID-!c-/-; Rag2-/-!c-/-) SRC human CD34 + (i.v. or i.f.) Bone marrow stem cell s CFSE/ DAPI/ OPN bone BM os endosteum Wilson et al. Genes & Dev 2004 c-kit + LRC + marrow BMT BMT 1º 2º 3º endosteum Clinical transplantation 5 6
2 Stem Cells - Definition: Cellular components of stem cell s in the adult bone marrow Cells capable to: self-renew i.e. produce undifferentiated differentiate and give rise to specialized Stem Cell Niche - Definition: Supportive bone marrow microenvironment structures that are essential for the long-term maintenance of a stable pool The is anatomically and functionally defined to have: endosteal compartment: proximity to trabecular bone perivascular compartment: proximity to sinusoidal Trabecular bone Endosteal Sinusoid endothelial (SEC) Precursor Osteoblasts - osteogenic CAR - (CXCL12 abundant vascular endothelium 7 lining the inner surface of the bone reticular) close to 8 the bone surface and endothelium CAR Osteoblasts Vascular Stroma fibroblasts Molecular interactions in the bone marrow Extrinsic Intrinsic mechanisms: Sinusoid mechanisms: cytokines endothelial (SEC) signalling molecules chemokines negative regulators (osteopontin) adhesion molecules VEGFR2 & 3 - VEGF cytoplasmic nuclear, incl. transcription factors proteases (MMP-9, cathepsin K) hormones (PTH, PGE2) epigenetic mechanisms DNA/histone modif. sympathetic nerves micrornas Gene expression oxygen status calcium concentration circadian rhytm quiescence self-renewal expansion Ang-1 - tie2 SCF - c-kit Flt3-L - Flt3 TPO - mpl Wnt - Frizzled Jagged/Delta - Notch OSTEOBLAST PTH, PGE2 Cadherins VCAM - VLA ICAM - LFA CXCL12 - CXCR4 HA - CD44 nerves cell-cell adhesion migration 9 Functional interactions in the bone marrow Hematopoietic homeostasis Migration Proliferation Differentiation Self-renewal Vascular Endosteal Engraftment Regeneration 5-FU IR Stress response Myelosuppressive injury damages SECs but not osteoblasts Administration of angiogenic factors may promote hematopoietic reconstitution after myeloablation through stabilization of vessels (VEGFR2 + VEGFR3 + sca110 - SEC) Fetal stem cell s Human placenta : reside in proximity to fetal blood vessels (pericytes and endothelial ) Robin et al. Cell 5: (2009) Mouse fetal liver : reside in perisinusoidal sites Iwasaki et al. Blood (2010) Stem cell quiescence: to prevent the stem cell exhaustion to protect stem from acquiring mutations leading to malignant transformation Developmental switch: fetal vs adult Bowie et al. PNAS 104: (2007) birth 3w 4w E14.5 adult Developmental Actively cycling expansion High self-renewal High GM output Quiescent Lower self-renewal Reduced GM output Homeostatic maintenance 11 Migration from active (vascular) s towards BM dormant (endosteal) s 12
3 reversibly switch from dormancy to self-renewal during homeostasis and repair Wilson et al. Cell 135:1118 (2008) Lin-Sca1 + CD117 + CD135 - CD34 - CD150 + CD48 - Homeostasis ± 15% ± 85% c-kit + LRC + marrow endosteum Dormant : - reduced metabolism & ribosomal biogenesis - reduced DNA replication (to protect from errors) - housed in dormant s (endosteal) as single - represent a reserve pool which can be used upon BM injury Dormant (d) LRC- activity high CD34 mrna low Injury Activated (a) Non-LRC- activity low CD34 mrna high Activated : - designated to proliferate & differentiate - present in vascular s where more oxygen is available to support the increased metabolism and cell-cycle activity < 1000 / mouse 5 divisions / life (mouse) every 145 days Injury: G-CSF, 5-FU IFN" activates dormant hematopoietic stem in vivo Essers et al. Nature 458: (2009) IFN" Leukemia Stem Cells Precursor (d) (a) Endosteal IFN" promotes the cell-cycle entry of (dormant and activated) resulting in proliferation, expansion, differentiation Cancer stem Normal stem and cancer share the ability to self-renew and many signaling pathways involved in the regulaton of normal stem cell development are mutated or epigenetically activated in cancer. Cancer Initiating Cell Models Cancer stem cell model Leukemia stem : Transformed hematopoietic stem or commited progenitor that have amplified or acquired the capacity for self-renewal, albeit in a poorly regulated fashion. Prog. 17 Wang and Dick,
4 Leukemia stem : 1 st identified cancer stem Induction of cell cycle entry eliminates human leukemia stem in a mouse model of AML Saito et al. Nature Biotech 28: (2010) Phenotype Function CD34 + CD38 - CD34 + CD38 + CD33+ CD44+ CD47+ CD71+ CD96+ CD117- CD123+ CD133+ CLL-1+ Human AML peripheral blood Serial assays: AML SL-IC CD34 + CD38 - NOD/SCID BM BM 1 o 2 o 3 o 1 o CFU 2 o CFU 3 o CFU 19 Combined G-CSF and AraC treatment effectively clears endosteal of 20 Leukemic stem resistant to conventional treatment lead to relapse and fatal outcome Current (novel) therapeutic studies Conventional treatment Leukemic cell growth Relapse Induction of cycling: IFN", G-CSF Targeting homing: CXCR4 antagonists Elimination of Degeneration Remission Interfering with adherence: Targeting surface markers: anti-cd44 mab anti-il3 r (CD123) mab Terminal differentiation Remission Preventing immune evasion: anti-cd47mab 1. Activation of dormant IFN"/G-CSF 2. Chemotherapy Targeted therapy CD47 is an adverse prognostic factor and therapeutic antibody target on human AML stem Jaiswal et al. Cell 138: (2009) Majet et al. Cell 138: (2009) SIRP" CD47 = No phagocytosis SIRP" CD47 Low levels of CD47 on avoid macrophages upon mobilization w. G-CSF High levels of CD47 on enhance survival due to decreased clearance..by macrophages General goal: creation of tumor non-permissive microenvironment BM is a dynamic microenvironment with high concentration of growth factors necessary for hematopoiesis, making it a highly permissive zone for cancer cell homing and survival. This is supported by the fact, that solid tumors very frequently home and metastasize to the BM. Hijacking the Elimination of Differentiation Remission BM stroma or Activation 1. of dormant IFN"/G-CSF Prevent immune evasion Promote Chemotherapy immunosurveillance23 Targeted therapy Seed or soil or both? 24
5 Generation of ES cell lines from human blastocysts The challenge of embryonic stem cell research: Thomson et al. Science 282:1145 (1998) Kaufman et al. PNAS 98:10716 (2001) Differentiation in vitro into various tissues! ES! ips! Therapeutic outlook Donated IVF blastocyst Inner cell mass immortal cell lines CFU s 25 enucleated Donated donor oocyte oocyte nuclear-transfer from adult cell Therapeutic Cloning (SCNT) Human ES with patient s genetic information = Immunologically-compatible tissue for transplantation 26 Human ES Goal: generation of engraftable hematopoietic Clinical use of ES-derived must address both maintenance and control of pluripotency, and also control of rejection danger. Control of growth and differentiation: Pluripotency may be a double-edged sward, since such have an increased potential for malignant transformation (teratoma formation). Uncontrolled differentiation of hes may lead to undesired progeny, overgrowth, or death of transplanted. Control the rejection: The likelihood of rejection requires strategies to circumvent or control the immune barriers (eg.with tolerogenic ES-derived cell lineages produced in parallel). 27 Human ips (induced pluripotent stem ) from adult dermal fibroblasts Oct3/4 Sox2 c-myc Klf4 fibroblasts Oct4 Sox2 Nanog Lin28 Takahashi et al. Cell 131:1 (2007) Yu et al. Science 318:1917 (2007) Zhou et al. Cell Stem Cell 4:381 (2009) Fusionproteins ± 20 days ips (pips) ES-like Differentiation into of all germ layers: Ectoderm Mesoderm Entoderm " Human ES morphology " Normal karyotype " Telomerase activity " Cell surface markers of ES " Gene expression profile of ES e.g. neural, heart muscle 28 Proof-of-principle papers on the therapeutic potential of ips 1 st report on correction of a disease in mouse : Treatment of sickle cell anemia mouse model with ips generated from autologous skin. Hanna et al. (Jaenisch s lab) Science 318:1920 (2007) Hu sickle cell anemia mouse h#s/h#s 70% PB were derived from ips Diff. to hematopoietic progenitors tail fibroblasts + Oct4/Sox2/klf4/c-Myc viruses ips ips Correction by gene targeting 29 30
6 1 st report on patient-specific corrected and reprogrammed ips : Disease-corrected haemopoietic progenitors from Fanconi anaemia ips Raya et al. Nature 460:53 (2009) Dermal fibroblasts 6 FA patients 1. Correction of defect lentiviral vectors: FANCA FANCD2 Succesful with: 3 FA patients-derived somatic 12/28 reprogramming attempts CD34 2. Reprogramming Viral vectors: Oct4 Sox2 Klf4 c-myc O nm MMC 1O nm MMC 31 ES SCNT Prospects for stem cell-based therapy of degenerative diseases ips CB- Stem cell choice: adult (multipotent) or embryonic (pluripotent) off-the-shelf from master-stocks (= cell banks) or customized for individual patients Stem cell number: increase homing and engraftment in tissue of choice develop drugs that augment the endogenous stem cell pools Stem cell immunogenicity: generate isogenic (genetically equivalent) : ips ES after nuclear transfer ( therapeutic cloning ) parthenogenetic embryos as ES cell source (pes) overcome the immune response: engineer deficient in class I...and II HLA genes/nk ligands or antagonizing immune responses Stem cell gene therapy: ES/iPS terato/cancerogenicity: control insertional mutagenesis 32 NSC Literature - Reviews: Stem - all aspects: Issue of Cell 132; Feb 22 (2008) and s: Kiel & Morrison, Nature 8: (2008) Jones & Wagers, Nature 9:11-21 (2008) Butler, Kobayashi & Rafii Nature 10: (2010) Trumpp, Essers & Wilson Nature Revs 10: (2010) Leukemia stem Chan & Huntly, Seminars in Oncology 35:326 (2008) Leukemic stem Lane, Scadden and Gilliland Blood 114: (2009) Cancer stem - targeting Trumpp & Wiestler, Nature Clinical Oncol 5:337 (2008) Sipkins NEJM 361: (2009) Goff & Jamieson Cell Stem Cell 6: (2010) 33
Haematopoietic stem cells
Haematopoietic stem cells Neil P. Rodrigues, DPhil NIH Centre for Biomedical Research Excellence in Stem Cell Biology Boston University School of Medicine neil.rodrigues@imm.ox.ac.uk Haematopoiesis: An
More informationHematopoiesis. - Process of generation of mature blood cells. - Daily turnover of blood cells (70 kg human)
Hematopoiesis - Process of generation of mature blood cells - Daily turnover of blood cells (70 kg human) 1,000,000,000,000 total cells 200,000,000,000 red blood cells 70,000,000,000 neutrophils Hematopoiesis
More informationHematopoiesis. BHS Liège 27/1/2012. Dr Sonet Anne UCL Mont-Godinne
Hematopoiesis BHS Liège 27/1/2012 Dr Sonet Anne UCL Mont-Godinne Hematopoiesis: definition = all the phenomenons to produce blood cells Leukocytes = White Blood Cells Polynuclear = Granulocytes Platelet
More informationMeeting Report. From December 8 to 11, 2012 at Atlanta, GA, U.S.A
Meeting Report Affiliation Department of Transfusion Medicine and Cell Therapy Name Hisayuki Yao Name of the meeting Period and venue Type of your presentation Title of your presentation The 54 th Annual
More informationHematopoiesis/Hematopoiesis Physiology
Hematopoiesis/Hematopoiesis Physiology Definitions Hematopoiesis is the process of continuous generation of mature blood cells in the bone marrow (Figure 1). Blood cells represent different kinds of mature
More informationGetting to the root of Cancer
Cancer Stem Cells: Getting to the root of Cancer Dominique Bonnet, Ph.D Senior Group Leader, Haematopoietic Stem Cell Laboratory Cancer Research UK, London Research Institute Venice, Sept 2009 Overview
More informationStem cells: units of development and regeneration. Fernando D. Camargo Ph.D. Whitehead Fellow Whitehead Institute for Biomedical Research.
Stem cells: units of development and regeneration Fernando D. Camargo Ph.D. Whitehead Fellow Whitehead Institute for Biomedical Research Concepts 1. Embryonic vs. adult stem cells 2. Hematopoietic stem
More informationCD34+ Cells: A Comparison of Stem and Progenitor Cells in Cord Blood, Peripheral Blood, and the Bone Marrow
White Paper September 2016 CD34+ Cells: A Comparison of Stem and Progenitor Cells in Cord Blood, Peripheral Blood, and the Bone Marrow Lily C. Trajman, PhD Introduction: Hematopoietic Stem Cells (HSCs)
More informationCytokines, adhesion molecules and apoptosis markers. A comprehensive product line for human and veterinary ELISAs
Cytokines, adhesion molecules and apoptosis markers A comprehensive product line for human and veterinary ELISAs IBL International s cytokine product line... is extremely comprehensive. The assays are
More informationDISCOVERING ATCC IMMUNOLOGICAL CELLS - MODEL SYSTEMS TO STUDY THE IMMUNE AND CARDIOVASCULAR SYSTEMS
DISCOVERING ATCC IMMUNOLOGICAL CELLS - MODEL SYSTEMS TO STUDY THE IMMUNE AND CARDIOVASCULAR SYSTEMS James Clinton, Ph.D. Scientist, ATCC February 19, 2015 About ATCC Founded in 1925, ATCC is a non-profit
More informationBlood 101 Introduction Blood and Marrow & Overview of Bone Marrow Failure Diseases. Dr. M. Sabloff October 16 th 2010
Blood 101 Introduction Blood and Marrow & Overview of Bone Marrow Failure Diseases Dr. M. Sabloff October 16 th 2010 Normal Marrow knee joint white is articular cartilage Adjacent to this is the red marrow
More informationStem cells. -Dr Dinesh Bhurani, MD, DM, FRCPA. Rajiv Gandhi Cancer Institute, Delhi, -Director, Department of Haematology and BMT
Stem cells -Dr Dinesh Bhurani, MD, DM, FRCPA -Director, Department of Haematology and BMT Rajiv Gandhi Cancer Institute, Delhi, Flow of presentation Update on stem cell uses Haematopoietic stem cell transplantation
More informationCancer and Cell Differentiation
Cancer and Cell Differentiation Recall The cell cycle consists of interphase, mitosis, and cytokinesis. Recall During S phase of interphase, the DNA is replicated to prepare for mitosis. Each daughter
More informationMyeloproliferative Disorders - D Savage - 9 Jan 2002
Disease Usual phenotype acute leukemia precursor chronic leukemia low grade lymphoma myeloma differentiated Total WBC > 60 leukemoid reaction acute leukemia Blast Pro Myel Meta Band Seg Lymph 0 0 0 2
More informationThe Role of the Embryonic Microenvironment in Hematopoietic Cell Development
The Role of the Embryonic Microenvironment in Hematopoietic Cell Development The Role of the Embryonic Microenvironment in Hematopoietic Cell Development De rol van de embryonale micro-omgeving op de
More informationProduction of the Formed Elements (Chapter 11) *
OpenStax-CNX module: m62120 1 Production of the Formed Elements (Chapter 11) * Ildar Yakhin Based on Production of the Formed Elements by OpenStax This work is produced by OpenStax-CNX and licensed under
More informationQuestion 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell?
Abbas Chapter 2: Sarah Spriet February 8, 2015 Question 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell? a. Dendritic cells b. Macrophages c. Monocytes
More informationRegenerative Medicine for Cardiomyocytes
Regenerative Medicine Regenerative Medicine for JMAJ 47(7): 328 332, 2004 Keiichi FUKUDA Assistant Professor, Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine Abstract: Heart
More informationStem Cells. Induced Stem Cells
Induced Stem Cells Stem Cells Mouse and human somatic cells can either be reprogrammed to a pluripotent state or converted to another lineage with a combination of transcription factors suggesting that
More informationTISSUE-SPECIFIC STEM CELLS
TISSUE-SPECIFIC STEM CELLS Concise Review: Multiple Niches for Hematopoietic Stem Cell Regulations IL-HOAN OH, a,b KYUNG-RIM KWON a,b a The Catholic High-Performance Cell Therapy Center, Division of Regenerative
More informationHematopoietic Stem Cells, Stem Cell Processing, and Transplantation
Hematopoietic Stem Cells, Stem Cell Processing, and Joseph (Yossi) Schwartz, M irector, Hemotherapy and Stem Cell Processing Facility Bone Marrow Can Cure: Leukemia Lymphoma Multiple Myeloma Genetic iseases:
More informationProduction of the Formed Elements *
OpenStax-CNX module: m46691 1 Production of the Formed Elements * OpenStax This work is produced by OpenStax-CNX and licensed under the Creative Commons Attribution License 3.0 By the end of this section,
More informationThe Role of Rac Signaling in The Perivascular Niche
The Role of Rac Signaling in The Perivascular Niche Felicia Ciuculescu Diaspora and Higher Education and Research Perspectives in Personalized Medicine- from Concept to Clinical Application Center for
More informationStem Cells And The Future of Regenerative Medicine. Dipnarine Maharaj, M. D., FACP
Stem Cells And The Future of Regenerative Medicine Dipnarine Maharaj, M. D., FACP The following potential conflict of interest relationships are germane to my presentation. Employment: South Florida Bone
More informationStem cells are undifferentiated cells which are maintained within a specific niche. A stem cell
Abstract Stem cells are undifferentiated cells which are maintained within a specific niche. A stem cell niche is a microenvironment of cells that maintain stem cell functionality, and one example is the
More informationMuscle Stem Cells in Regeneration
Muscle Stem Cells in Regeneration Dr. F Jeffrey Dilworth BIM6028/SMC6052 Lecture (February 11, 2016) Duchenne Muscular Dystrophy is an X-linked genetic disorder that affects 1 in 3500 males Wells et al,
More informationTransplantation - Challenges for the future. Dr Gordon Cook S t James s Institute of Oncology, Leeds Teaching Hospitals Trust
Transplantation - Challenges for the future Dr Gordon Cook S t James s Institute of Oncology, Leeds Teaching Hospitals Trust Bone Marrow Transplantation Timeline, 1957-2006 Appelbaum F. N Engl J Med 2007;357:1472-1475
More informationTARGETED THERAPY FOR CHILDHOOD CANCERS
TARGETED THERAPY FOR CHILDHOOD CANCERS AZIZA SHAD, MD AMEY DISTINGUISHED PROFESSOR OF PEDIATRIC HEMATOLOGY ONCOLOGY, BLOOD AND MARROW TRANSPLANTATION LOMBARDI CANCER CENTER GEORGETOWN UNIVERSITY HOSPITAL
More informationOne Day BMT Course by Thai Society of Hematology. Management of Graft Failure and Relapsed Diseases
One Day BMT Course by Thai Society of Hematology Management of Graft Failure and Relapsed Diseases Piya Rujkijyanont, MD Division of Hematology-Oncology Department of Pediatrics Phramongkutklao Hospital
More informationstem cell products Basement Membrane Matrix Products Rat Mesenchymal Stem Cell Growth and Differentiation Products
stem cell products Basement Membrane Matrix Products Rat Mesenchymal Stem Cell Growth and Differentiation Products Stem Cell Qualified Extracellular Matrix Proteins Stem cell research requires the finest
More informationGeneration of post-germinal centre myeloma plasma B cell.
Generation of post-germinal centre myeloma. DNA DAMAGE CXCR4 Homing to Lytic lesion activation CD38 CD138 CD56 Phenotypic markers Naive Secondary lymphoid organ Multiple myeloma is a malignancy of s caused
More informationLymphoid architecture & Leukocyte recirculation. Thursday Jan 26th, 2017
Lymphoid architecture & Leukocyte recirculation Thursday Jan 26th, 2017 Topics The life of immune cells Where are they born? Where are they educated? Where do they function? How do they get there? The
More informationHumanized models to study immunity and to accelerate the development of new solutions for human health
Humanized models to study immunity and to accelerate the development of new solutions for human health Fondation Mérieux Conference Center April 27, 2017 Next generation humanized mouse models for normal
More informationReviews. This Review is part of a thematic series on Cellular Therapy, which includes the following articles:
Reviews This Review is part of a thematic series on Cellular Therapy, which includes the following articles: The Stem Cell Movement Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy
More informationHematopoetic Stem Cell Therapies in TURKIYE
Hematopoetic Stem Cell Therapies in TURKIYE World Location of transplant centers participating in CIBMTR (2010) Dr. Mustafa ÇETİN Mustafa CETIN, M.D. Erciyes University Medical Faculty Kayseri-TURKIYE
More informationBone Marrow Stroma in Myelodysplastic Syndromes
Bone Marrow Stroma in Myelodysplastic Syndromes Universidad de Salamanca Prof Mª M Consuelo del Cañizo Hematology Dept. University Hospital, Salamanca SPAIN Bone marrow stroma in MDS Introduction Mesenchymal
More informationUnderstanding the role of ex vivo T cell depletion
Prevention of graftversus-host disease (GVHD) Understanding the role of ex vivo T cell depletion Information for patients undergoing allogeneic stem cell transplantation in AML and their families 2 This
More informationProf. Dr. Malak A. Al-yawer
Bone marrow Is a soft connective tissue occupies the medullary cavity of long bones and all the spaces between the trabeculae of spongy bone. It accounts for approximately 5% of the body weight in humans.
More informationBL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES. Overview and Mechanism of Action Dr.
BL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES Overview and Mechanism of Action Dr. Leah Klapper, CSO 88 BL-8040: Novel CXCR4 Antagonist For Hematological Cancers Indications:
More informationANAT3231: lectures overview
ANAT3231: lectures overview Stem Cell Biology Stem Cell Technology Resources: http://php.med.unsw.edu.au/cell biology/ Essential Cell Biology 3 rd edition Alberts Dr Annemiek Beverdam School of Medical
More informationOncolytic Virotherapy: Targeting Cancer Stem Cells
Oncolytic Virotherapy: Targeting Cancer Stem Cells Cancer Stem Cells (CSCs) or Cancer Initiating Cells (CICs) A consensus of five defining criteria has been established to affirm the existence of CICs:
More informationANAT3231: lectures overview
ANAT3231: lectures overview Stem Cell Biology Stem Cell Technology Resources: http://php.med.unsw.edu.au/cell biology/ Essential Cell Biology 3 rd edition Alberts Dr Annemiek Beverdam School of Medical
More informationScientific report: Delineating cellular stages and regulation of human NK cell development to improve NK cell-based therapy for cancer (Dnr )
Scientific report: Delineating cellular stages and regulation of human NK cell development to improve NK cell-based therapy for cancer (Dnr 130259) The main goal of this project focuses on establishing
More informationChildhood hematopoiesis and hematological features. Yongmin Tang Dept. Hematology-oncology Chidlren s Hospital Zhejiang University School of medicine
Childhood hematopoiesis and hematological features Yongmin Tang Dept. Hematology-oncology Chidlren s Hospital Zhejiang University School of medicine Questions: How much have you known about our hematopoietic
More informationCANCER IMMUNOPATHOLOGY. Eryati Darwin Faculty of Medicine Andalas University
CANCER IMMUNOPATHOLOGY Eryati Darwin Faculty of Medicine Andalas University Padang 18 Mei 2013 INTRODUCTION Tumor: cells that continue to replicate, fail to differentiate into specialized cells, and become
More informationLeukine. Leukine (sargramostim) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.10.08 Subject: Leukine Page: 1 of 6 Last Review Date: March 13, 2014 Leukine Description Leukine (sargramostim)
More informationIN THE NAME OF GOD CANCER CELL REPROGRAMING
IN THE NAME OF GOD CANCER CELL REPROGRAMING Qazvin university of medical science Presented by: fatane abedy GUIDANCE: Dr. gheibi 1 CONTENT: CANCER REPROGRAMMING OSKM microrna PROBLEM AND ADVANTAGE REFRANCE
More informationLeukine. Leukine (sargramostim) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Leukine Page: 1 of 6 Last Review Date: November 30, 2018 Leukine Description Leukine (sargramostim)
More informationHSC Niche Biology and HSC Expansion Ex Vivo
Feature Review HSC Niche Biology and HSC Expansion Ex Vivo Sachin Kumar 1, * and Hartmut Geiger 1,2,3, * Hematopoietic stem cell (HSC) transplantation can restore a new functional hematopoietic system
More information4. TEXTBOOK: ABUL K. ABBAS. ANDREW H. LICHTMAN. CELLULAR AND MOLECULAR IMMUNOLOGY. 5 TH EDITION. Chapter 2. pg
LECTURE: 03 Title: CELLS INVOLVED IN THE IMMUNE RESPONSE LEARNING OBJECTIVES: The student should be able to: Identify the organs where the process of the blood formation occurs. Identify the main cell
More informationTissue renewal and Repair. Nisamanee Charoenchon, PhD Department of Pathobiology, Faculty of Science
Tissue renewal and Repair Nisamanee Charoenchon, PhD Email: nisamanee.cha@mahidol.ac.th Department of Pathobiology, Faculty of Science Topic Objectives 1. Describe processes of tissue repair, regeneration
More informationTargeting tumour associated macrophages in anti-cancer therapies. Annamaria Gal Seminar Series on Drug Discovery Budapest 5 January 2018
Targeting tumour associated macrophages in anti-cancer therapies Annamaria Gal Seminar Series on Drug Discovery Budapest 5 January 2018 Macrophages: Professional phagocytes of the myeloid lineage APC,
More informationSeptember 20, Submitted electronically to: Cc: To Whom It May Concern:
History Study (NOT-HL-12-147), p. 1 September 20, 2012 Re: Request for Information (RFI): Building a National Resource to Study Myelodysplastic Syndromes (MDS) The MDS Cohort Natural History Study (NOT-HL-12-147).
More informationThe Immune System. A macrophage. ! Functions of the Immune System. ! Types of Immune Responses. ! Organization of the Immune System
The Immune System! Functions of the Immune System! Types of Immune Responses! Organization of the Immune System! Innate Defense Mechanisms! Acquired Defense Mechanisms! Applied Immunology A macrophage
More informationCLINICAL USE OF CELLULAR SUBPOPULATION ANALYSIS IN BM
CLINICAL USE OF CELLULAR SUBPOPULATION ANALYSIS IN BM CANCER RESEARCH CENTRE, UNIVERSITY AND UNIVERSITY HOSPITAL OF SALAMANCA (SPAIN)( Sao Paulo, 18th of April, 2009 IDENTIFICATION OF HPC (I) 1.- In vivo
More informationCancer Stem Cells & Glioblastoma
Cancer Stem Cells & Glioblastoma JP Hugnot «Brain plasticity, Neural stem cells and Glial tumors» INSERM U1051-UM2 Institut des Neurosciences de Montpellier Montpellier 1-Stem cells and Brain Stem Cells
More informationUMBILICAL CORD BLOOD STEM CELLS EXPANDED IN THE PRESENCE OF NICOTINAMIDE (NICORD) PROVIDE LONG TERM MULITI-LINEAGE ENGRAFTMENT
UMBILICAL CORD BLOOD STEM CELLS EXPANDED IN THE PRESENCE OF NICOTINAMIDE (NICORD) PROVIDE LONG TERM MULITI-LINEAGE ENGRAFTMENT Mitchell E. Horwitz, MD Duke University Medical Center Duke Cancer Institute
More informationThe nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive hematopoietic cells
Research article The nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive hematopoietic cells Sungho Kook, 1 Joonseok Cho, 1 Sean Bong Lee, 2 and Byeong-Chel Lee 1 1 University of Pittsburgh
More informationThe National Marrow Donor Program. Graft Sources for Hematopoietic Cell Transplantation. Simon Bostic, URD Transplant Recipient
1988 199 1992 1994 1996 1998 2 22 24 26 28 21 212 214 216 218 Adult Donors Cord Blood Units The National Donor Program Graft Sources for Hematopoietic Cell Transplantation Dennis L. Confer, MD Chief Medical
More informationRole of Inflammatory and Progenitor Cells in Pulmonary Vascular Remodeling: Potential Role for Targeted Therapies. Traditional Hypothesis Stress
3/1/212 Role of Inflammatory and Progenitor Cells in Pulmonary Vascular Remodeling: Potential Role for Targeted Therapies K.R. Stenmark University of Colorado Denver, CO 845 Prominent Fibroproliferative
More informationAccelerate Your Research with Conversant Bio
Accelerate Your Research with Conversant Bio 400+ Participating MDs 50+ Partner sites for tissue procurement Continuous expansion of sourcing capabilities Closely monitored chain of custody Full regulatory
More informationBone Marrow Transplantation and the Potential Role of Iomab-B
Bone Marrow Transplantation and the Potential Role of Iomab-B Hillard M. Lazarus, MD, FACP Professor of Medicine, Director of Novel Cell Therapy Case Western Reserve University 1 Hematopoietic Cell Transplantation
More informationDevelopment of Highly Active Anti-Leukemia Stem Cell Therapy (HALT)
Development of Highly Active Anti-Leukemia Stem Cell Therapy (HALT) CIRM/CSCC disease team grant CIRM PI: D. Carson co-pi: C. Jamieson CSCC PI: J. Dick co-pi: J. Wang Project leaders: ROR1 mab Development:
More informationPhD THESIS Epigenetic mechanisms involved in stem cell differentiation
Romanian Academy Institute of Cellular Biology and Pathology "Nicolae Simionescu" PhD THESIS Epigenetic mechanisms involved in stem cell differentiation Coordinator: Acad. Maya Simionescu PhD Student:
More informationStrategic delivery: Setting standards Increasing and. Details: Output: Demonstrating efficiency. informing choice.
Strategic delivery: Setting standards Increasing and informing choice Demonstrating efficiency economy and value Details: Meeting Scientific and Clinical Advances Advisory Committee Agenda item 6 Paper
More informationCurrent Developments in Mobilization of Hematopoietic Stem and Progenitor Cells and Their Interaction with Niches in Bone Marrow
Review Article DOI: 10.1159/000477262 Received: March 2, 2017 Accepted: May 4, 2017 Published online: May 29, 2017 Current Developments in Mobilization of Hematopoietic Stem and Progenitor Cells and Their
More informationCancer as a disease of development; Developmental therapies: Anti- Angiogenesis; Stem cells and tissue regeneration.
Cancer as a disease of development; Developmental therapies: Anti- Angiogenesis; Stem cells and tissue regeneration Mitesh Shrestha What is Cancer? Unrestricted cell growth: tumor cell population 1x10^9
More informationBONE MARROW PROF. DR. MALAK A. AL-YAWER
Objectives state the types of bone marrow Identify the major sites of hematopoiesis in the fetus and normal adult. outline the compartments of red bone marrow describe the types and distinctive characteristic
More informationEffective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features
Effective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features Loretta Gammaitoni, Lidia Giraudo, Valeria Leuci, et al. Clin Cancer Res
More informationLeukine. Leukine (sargramostim) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.85.08 Subject: Leukine Page: 1 of 5 Last Review Date: September 15, 2017 Leukine Description Leukine
More informationLong-term innate immune memory via effects on bone marrow progenitors
Long-term innate immune memory via effects on bone marrow progenitors Helen S Goodridge, PhD helen.goodridge@csmc.edu Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, USA Fondation
More informationJournal Club WS 2012/13 Stefanie Nickl
Journal Club WS 2012/13 Stefanie Nickl Background Mesenchymal Stem Cells First isolation from bone marrow 30 ys ago Isolation from: spleen, heart, skeletal muscle, synovium, amniotic fluid, dental pulp,
More informationCRISPR-mediated Editing of Hematopoietic Stem Cells for the Treatment of β-hemoglobinopathies
CRISPR-mediated Editing of Hematopoietic Stem Cells for the Treatment of β-hemoglobinopathies Jennifer Gori American Society of Gene & Cell Therapy May 11, 2017 editasmedicine.com 1 Highlights Developed
More informationStem Cells. Keith Channon. Department of Cardiovascular Medicine University of Oxford John Radcliffe Hospital, Oxford
Stem Cells Keith Channon Department of Cardiovascular Medicine University of Oxford John Radcliffe Hospital, Oxford Adult Stem Cells Unique cells that are capable of self-renewal Have the ability to differentiate
More informationBCR-ABL - LSK BCR-ABL + LKS - (%)
Marker Clone BCR-ABL + LSK (%) BCR-ABL + LKS - (%) BCR-ABL - LSK (%) P value vs. BCR-ABL + LKS - P value vs. BCR-ABL - LSK CD2 RM2-5 12.9 ± 3.6 36.7 ± 6.5 19.3 ± 2.4 0.01 0.10 CD5 53-7.3 13.9 ± 3.2 20.8
More informationHEMATOLOGIC MALIGNANCIES BIOLOGY
HEMATOLOGIC MALIGNANCIES BIOLOGY Failure of terminal differentiation Failure of differentiated cells to undergo apoptosis Failure to control growth Neoplastic stem cell FAILURE OF TERMINAL DIFFERENTIATION
More informationMechanisms of Resistance to Antiangiogenic. Martin J. Edelman, MD University of Maryland Greenebaum Cancer Center Dresden, 2012
Mechanisms of Resistance to Antiangiogenic Agents Martin J. Edelman, MD University of Maryland Greenebaum Cancer Center Dresden, 2012 Angiogenesis: A fundamental attribute of cancer Premise of Anti-angiogenic
More informationMobilization of hematopoietic stem and leukemia cells
Review Mobilization of hematopoietic stem and leukemia cells Mark A. Schroeder and John F. DiPersio 1 Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri,
More informationMACROPHAGE "MONOCYTES" SURFACE RECEPTORS
LECTURE: 13 Title: MACROPHAGE "MONOCYTES" SURFACE RECEPTORS LEARNING OBJECTIVES: The student should be able to: Describe the blood monocytes (size, and shape of nucleus). Enumerate some of the monocytes
More informationResident cardiac stem cells: how to find and use them
Resident cardiac stem cells: how to find and use them G. Hasenfuß Cardiology and Pneumology Heart Research Center Göttingen Georg-August-University Göttingen Definition: Stem cell Selfrenewal Stem cell
More informationNormal & Leukaemic haematopoiesis. Dr. Liu Te Chih Dept of Haematology / Oncology National University Health Services Singapore
Normal & Leukaemic haematopoiesis 2010 Dr. Liu Te Chih Dept of Haematology / Oncology National University Health Services Singapore Use of Immunophenotyping today Lineage assignment Differentiation of
More informationAn Introduction to Bone Marrow Transplant
Introduction to Blood Cancers An Introduction to Bone Marrow Transplant Rushang Patel, MD, PhD, FACP Florida Hospital Medical Group S My RBC Plt Gran Polycythemia Vera Essential Thrombocythemia AML, CML,
More informationMesenchymal Stem Cells to Repair Vascular Damage after Chemotherapy: Past, Present and Future
Mesenchymal Stem Cells to Repair Vascular Damage after Chemotherapy: Past, Present and Future Cell Therapy 2014 Las Vegas, NV, USA Sulaiman Al-Hashmi, PhD Sultan Qaboos University Oman What are MSCs? Stem
More informationChapter 3, Part A (Pages 37-45): Leukocyte Migration into Tissues
Allergy and Immunology Review Corner: Chapter 3, Part A (pages 37-45) of Cellular and Molecular Immunology (Seventh Edition), by Abul K. Abbas, Andrew H. Lichtman and Shiv Pillai. Chapter 3, Part A (Pages
More informationThe future of HSCT. John Barrett, MD, NHBLI, NIH Bethesda MD
The future of HSCT John Barrett, MD, NHBLI, NIH Bethesda MD Transplants today Current approaches to improve SCT outcome Optimize stem cell dose and source BMT? PBSCT? Adjusting post transplant I/S to minimize
More informationStem cells and Cancer. John Glod. December 2, 2009
Stem cells and Cancer John Glod Lehigh University Lehigh University December 2, 2009 The Tumor Microenvironment Littlepage et al Cancer Cell 2005 Cancer Stem Cells A small group of cells within the larger
More informationNeutrophil Recovery: The. Posttransplant Recovery. Bus11_1.ppt
Neutrophil Recovery: The First Step in Posttransplant Recovery No conflicts of interest to disclose Bus11_1.ppt Blood is Made in the Bone Marrow Blood Stem Cell Pre-B White cells B Lymphocyte T Lymphocyte
More informationModeling Developmental Hematopoiesis Using Pluripotent Stem Cells
Modeling Developmental Hematopoiesis Using Pluripotent Stem Cells Christopher Sturgeon February 14, 2017 Pluripotent Stem Cells self-renewal hpsc Mesoderm blood cardiovascular muscle Endoderm lung liver
More informationBiology of Immune Aging
Biology of Immune Aging Jorg J. Goronzy Stanford University Immune deficiency Increase morbidity and mortality from infections Poor vaccine responses Cancer Immune Aging Chronic inflammation Coronary artery
More informationSTEM CELL RESEARCH: MEDICAL PROGRESS WITH RESPONSIBILITY
STEM CELL RESEARCH: MEDICAL PROGRESS WITH RESPONSIBILITY A REPORT FROM THE CHIEF MEDICAL OFFICER S EXPERT GROUP REVIEWING THE POTENTIAL OF DEVELOPMENTS IN STEM CELL RESEARCH AND CELL NUCLEAR REPLACEMENT
More informationAnimal Models to Understand Immunity
Animal Models to Understand Immunity Hussein El Saghire hesaghir@sckcen.be Innate Adaptive immunity Immunity MAPK and NF-kB TLR pathways receptors Fast Slow Non-specific Specific NOD-like receptors T-cell
More informationEHA an overview. Christine Chomienne EHA President.
EHA an overview Christine Chomienne EHA President www.ehaweb.org EHA activities Career development Calls are open now EHA Learning Center Annual congress EHA promotes excellence in research, education
More informationFlow Cytometry. What is flow cytometry?
Flow Cytometry Flow Cytometry What is flow cytometry? Flow cytometry is a popular laser-based technology to analyze the characteristics of cells or particles. It is predominantly used to measure fluorescence
More informationThe Role of Microenvironment in the Control of Tumor Angiogenesis
The Role of Microenvironment in the Control of Tumor Angiogenesis Domenico Ribatti The Role of Microenvironment in the Control of Tumor Angiogenesis Domenico Ribatti Department of Basic Medical Sciences,
More informationCell signalling pathways in the HSC niche. Dr. Abdullah Aljedai
Cell signalling pathways in the HSC niche Dr. Abdullah Aljedai 31-10-2009 Learning objectives & resources 1- To introduce the concept of cell signaling process in the haemopoietic system. 2- To outline
More informationFormation of Blood Cells
Hematopoiesis Lecture Objectives Name organs responsible for hematopoiesis in the fetus. List the developmental stages of hematopoiesis both prenatally and postnatally. Outline the major steps of post
More informationAplastic Anemia: Understanding your Disease and Treatment Options
Aplastic Anemia: Understanding your Disease and Treatment Options No financial relationships or commercial interest related to the content of this presentation Josh Sasine, MD, PhD Hematopoietic Cell Transplant
More informationThe Hierarchical Organization of Normal and Malignant Hematopoiesis
The Hierarchical Organization of Normal and Malignant Hematopoiesis NORMAL Hematopoie2c Stem Cell (HSC) Leukemia Stem Cells (LSC) MPP MLP CMP Leukemic Progenitors MEP GMP B/NK ETP Leukemic Blasts Erythrocytes
More informationUmbilical Cord Blood Transplantation
Umbilical Cord Blood Transplantation Current Results John E. Wagner, M.D. Blood and Marrow Transplant Program and Stem Cell Institute University of Minnesota Donor Choices Unrelated Marrow/PBSC Results
More information