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Comparative Gene Expression Profiling of Stromal Cell Matrices
ell Res C ea m rc te h S & f o T h l Journal of Tiwari et al., J Stem Cell Res Ther 2013, 3:4 e a r n a r p u DOI: 10.4172/2157-7633.1000152 y o J ISSN: 2157-7633 Stem Cell Research & Therapy Research Article Open Access Comparative Gene Expression Profiling of Stromal Cell Matrices that Support Expansion of Hematopoietic Stem/Progenitor Cells Abhilasha Tiwari1,2, Christophe Lefevre2, Mark A Kirkland2*, Kevin Nicholas2 and Gopal Pande1* 1CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India 2Deakin University, Waurn Ponds, Geelong, VIC, Australia Abstract The bone marrow microenvironment maintains a stable balance between self-renewal and differentiation of hematopoietic stem/progenitor cells (HSPCs). This microenvironment, also termed the “hematopoietic niche”, is primarily composed of stromal cells and their extracellular matrices (ECM) that jointly regulate HSPC functions. Previously, we have demonstrated that umbilical cord blood derived HSPCs can be maintained and expanded on stromal cell derived acellular matrices that mimic the complexity of the hematopoietic niche. The results indicated that matrices prepared at 20% O2 with osteogenic medium (OGM) were best suited for expanding committed HSPCs, whereas, matrices prepared at 5% O2 without OGM were better for primitive progenitors. Based upon these results we proposed that individual constituents of these matrices could be responsible for regulation of specific HSPC functions. To explore this hypothesis, we have performed comparative transcriptome profiling of these matrix producing cells, which identified differential expression of both known niche regulators, such as Wnt4, Angpt2, Vcam and Cxcl12, as well as genes not previously associated with HSPC regulation, such as Depp. -
How I Treat Myelofibrosis
From www.bloodjournal.org by guest on October 7, 2014. For personal use only. Prepublished online September 16, 2014; doi:10.1182/blood-2014-07-575373 How I treat myelofibrosis Francisco Cervantes Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml Advance online articles have been peer reviewed and accepted for publication but have not yet appeared in the paper journal (edited, typeset versions may be posted when available prior to final publication). Advance online articles are citable and establish publication priority; they are indexed by PubMed from initial publication. Citations to Advance online articles must include digital object identifier (DOIs) and date of initial publication. Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved. From www.bloodjournal.org by guest on October 7, 2014. For personal use only. Blood First Edition Paper, prepublished online September 16, 2014; DOI 10.1182/blood-2014-07-575373 How I treat myelofibrosis By Francisco Cervantes, MD, PhD, Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain Correspondence: Francisco Cervantes, MD, Hematology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. Phone: +34 932275428. -
Thrombopoietin Supports the Continuous Growth of Cytokine-Dependent Human Leukemia Cell Lines HG Drexler, M Zaborski and H Quentmeier
Leukemia (1997) 11, 541–551 1997 Stockton Press All rights reserved 0887-6924/97 $12.00 Thrombopoietin supports the continuous growth of cytokine-dependent human leukemia cell lines HG Drexler, M Zaborski and H Quentmeier DSMZ-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Mascheroder Weg 1 B, D-38124 Braunschweig, Germany Hematopoiesis is a complex process of regulated cellular pro- nate membrane receptor. This binding triggers a series of intra- liferation and differentiation from the primitive stem cells to the cellular mediators involved in the growth factor’s signaling final fully differentiated cell. The long and extensive search for a factor specifically regulating megakaryocytopoiesis led to the pathways. Recently, a novel hematopoietic growth factor, cloning of a hormone, here called thrombopoietin (TPO), that termed thrombopoietin (TPO), was cloned and shown to be a specifically promotes proliferation and differentiation of the megakaryocytic lineage-associated growth and differentiation megakaryocytic lineage. The availability of recombinant TPO factor. Binding of TPO to its receptor, c-MPL, mediates plei- and its imminent clinical use has made a more detailed under- otropic effects on megakaryocyte development in vitro and in standing of its effects on hematopoietic cells more urgent. Nor- vivo. TPO is clearly the primary regulator of this cell lineage mal megakaryocyto- and thrombopoiesis occurs predomi- nantly in the bone marrow, a difficult organ to study in situ, acting at all levels of megakaryocytopoiesis and thrombopo- particularly in humans, due to the low numbers of megakary- iesis (reviewed in Ref. 1). ocytic progenitors and the consequent difficult isolation as The availability of TPO will be of considerable clinical pure populations. -
Side Effects of Molecular-Targeted Therapies in Solid Cancers : a New Challenge in Cancer Therapy Management
Side effects of molecular-targeted therapies in solid cancers : a new challenge in cancer therapy management Ahmad Awada, MD, PhD Medical Oncology Clinic Institut Jules Bordet Université Libre de Bruxelles (U.L.B.) Brussels, Belgium PLAN OF THE LECTURE 1. Concept 2. Achievements on the management of side effects 3. Remaining challenges 4. New challenges with the development of molecular-targeted therapies 5. Conclusions Reducing the cancer- related problems and the side effects of the SUPPORTIVE CARE = medicine administered to treat the disease SIDE EFFECTS OF CANCER THERAPY: ACHIEVEMENTS Side effect Preventive & Therapeutic intervention • Febrile neutropenia • G-CSF, Anti-infectives • Anemia • Epoetine •Mucositis •Laser therapy, Palifermin • Nausea & Vomiting • 5-HT3 and neurokin-1-receptor antagonists •Thromboembolic •LMW Heparin events • Cardiomyopathy • Liposomal formulations, Dexrazonane (anthracyclines) MANAGEMENT OF SIDE EFFECTS : REMAINING CHALLENGES • Alopecia • Thrombocytopenia ( ! Promising Thrombopoietin- mimetics are under investigation) • Asthenia MOLECULAR TARGETS AND THERAPIES (1) Drug Class Mechanism of action Main tumor indication Gefitinib* Small molecule TK inhibitor of EGFR NSCLC (Iressa) Erlotinib* Small molecule TK inhibitor of EGFR NSCLC (Tarceva) Cetuximab* Monoclonal Antibody Blocks EGFR Colorectal, Head & (Erbitux) Neck, NSCLC Monoclonal Panitumumab* Antibody Blocks EGFR Colorectal (Vectibix) * Investigational in BC TK : tyrosine kinase; EGFR : epidermal growth factor receptor MOLECULAR TARGETS AND THERAPIES -
DOPTELET (Avatrombopag) RATIONALE for INCLUSION IN
DOPTELET (avatrombopag) RATIONALE FOR INCLUSION IN PA PROGRAM Background Doptelet is a thrombopoietin (TPO) receptor agonist used to increase platelet counts. Doptelet (avatrombopag) is an orally bioavailable, small molecule TPO receptor agonist that stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells resulting in an increased production of platelets. Doptelet does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production (1). Regulatory Status FDA approved indication: Doptelet is a thrombopoietin receptor agonist indicated for the treatment of: (1) 1. Thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. 2. Thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment. Doptelet should not be administered to patients with chronic liver disease in an attempt to normalize platelet counts (1). Doptelet is a thrombopoietin (TPO) receptor agonist and TPO receptor agonists have been associated with thrombotic and thromboembolic complications in patients with chronic liver disease. A Doppler ultrasound is a noninvasive test that can be used to estimate the blood flow through blood vessels by bouncing high-frequency sound waves (ultrasound) off circulating red blood cells. A Doppler ultrasound may help determine if Doptelet therapy is appropriate for a patient (1-2). The safety and effectiveness of Doptelet in pediatric patients have not been established (1). Summary Doptelet is a thrombopoietin (TPO) receptor agonist used to increase platelet counts. Doptelet (avatrombopag) is an orally bioavailable, small molecule TPO receptor agonist that stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells resulting in an increased production of platelets. -
Insights Into the Cellular Mechanisms of Erythropoietin-Thrombopoietin Synergy
Papayannopoulou et al.: Epo and Tpo Synergy Experimental Hematology 24:660-669 (19961 661 @ 1996 International Society for Experimental Hematology Rapid Communication ulation with fluorescence microscopy. Purified subsets were grown in plasma clot and methylcellulose clonal cultures and in suspension cultures using the combinations of cytokines Insights into the cellular mechanisms cadaveric bone marrow cells obtained from Northwest described in the text. Single cells from the different subsets Center, Puget Sound Blood Bank (Seattle, WA), were were. also deposited (by FACS) on 96-well plates containing of erythropoietin-thrombopoietin synergy washed, and incubated overnight in IMDM with 10% medmm and cytokines. Clonal growth from single-cell wells calf serum on tissue culture plates to remove adherent were double-labeled with antiglycophorin A-PE and anti Thalia Papayannopoulou, Martha Brice, Denise Farrer, Kenneth Kaushansky From the nonadherent cells, CD34+ cells were isolated CD41- FITC between days 10 and 19. direct immunoadherence on anti-CD34 monoclonal anti University of Washington, Department of Medicine, Seattle, WA (mAb)-coated plates, as previously described [15]. Purity Immunocytochemistry Offprint requests to: Thalia Papayannopoulou, MD, DrSci, University of Washington, isolated CD34+ cells ranged from 80 to 96% by this For immunocytochemistry, either plasma clot or cytospin cell Division of Hematology, Box 357710, Seattle, WA 98195-7710 od. Peripheral blood CD34 + cells from granulocyte preparations were used. These were fixed at days 6-7 and (Received 24 January 1996; revised 14 February 1996; accepted 16 February 1996) ulating factor (G-CSF)-mobilized normal donors 12-13 with pH 6.5 Histochoice (Amresco, Solon, OH) and provided by Dr. -
Dickkopf-1 Promotes Hematopoietic Regeneration Via Direct and Niche-Mediated Mechanisms
ARTICLES Dickkopf-1 promotes hematopoietic regeneration via direct and niche-mediated mechanisms Heather A Himburg1,7, Phuong L Doan2,7, Mamle Quarmyne1,3, Xiao Yan1,3, Joshua Sasine1, Liman Zhao1, Grace V Hancock4, Jenny Kan1, Katherine A Pohl1, Evelyn Tran1, Nelson J Chao2, Jeffrey R Harris2 & John P Chute1,5,6 The role of osteolineage cells in regulating hematopoietic stem cell (HSC) regeneration following myelosuppression is not well understood. Here we show that deletion of the pro-apoptotic genes Bak and Bax in osterix (Osx, also known as Sp7 transcription factor 7)-expressing cells in mice promotes HSC regeneration and hematopoietic radioprotection following total body irradiation. These mice showed increased bone marrow (BM) levels of the protein dickkopf-1 (Dkk1), which was produced in Osx-expressing BM cells. Treatment of irradiated HSCs with Dkk1 in vitro increased the recovery of both long-term repopulating HSCs and progenitor cells, and systemic administration of Dkk1 to irradiated mice increased hematopoietic recovery and improved survival. Conversely, inducible deletion of one allele of Dkk1 in Osx-expressing cells in adult mice inhibited the recovery of BM stem and progenitor cells and of complete blood counts following irradiation. Dkk1 promoted hematopoietic regeneration via both direct effects on HSCs, in which treatment with Dkk1 decreased the levels of mitochondrial reactive oxygen species and suppressed senescence, and indirect effects on BM endothelial cells, in which treatment with Dkk1 induced epidermal growth factor (EGF) secretion. Accordingly, blockade of the EGF receptor partially abrogated Dkk1-mediated hematopoietic recovery. These data identify Dkk1 as a regulator of hematopoietic regeneration and demonstrate paracrine cross-talk between BM osteolineage cells and endothelial cells in regulating hematopoietic reconstitution following injury. -
The Molecular Mechanisms That Control Thrombopoiesis
The molecular mechanisms that control thrombopoiesis Kenneth Kaushansky J Clin Invest. 2005;115(12):3339-3347. https://doi.org/10.1172/JCI26674. Review Series Our understanding of thrombopoiesis — the formation of blood platelets — has improved greatly in the last decade, with the cloning and characterization of thrombopoietin, the primary regulator of this process. Thrombopoietin affects nearly all aspects of platelet production, from self-renewal and expansion of HSCs, through stimulation of the proliferation of megakaryocyte progenitor cells, to support of the maturation of these cells into platelet-producing cells. The molecular and cellular mechanisms through which thrombopoietin affects platelet production provide new insights into the interplay between intrinsic and extrinsic influences on hematopoiesis and highlight new opportunities to translate basic biology into clinical advances. Find the latest version: https://jci.me/26674/pdf Review series The molecular mechanisms that control thrombopoiesis Kenneth Kaushansky Department of Medicine, Division of Hematology/Oncology, University of California, San Diego, San Diego, California, USA. Our understanding of thrombopoiesis — the formation of blood platelets — has improved greatly in the last decade, with the cloning and characterization of thrombopoietin, the primary regulator of this process. Thrombopoietin affects nearly all aspects of platelet production, from self-renewal and expansion of HSCs, through stimulation of the proliferation of megakaryocyte progenitor cells, to support of the maturation of these cells into platelet-pro- ducing cells. The molecular and cellular mechanisms through which thrombopoietin affects platelet production provide new insights into the interplay between intrinsic and extrinsic influences on hematopoiesis and highlight new opportunities to translate basic biology into clinical advances. -
Supporting Online Material
1 2 3 4 5 6 7 Supplementary Information for 8 9 Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic 10 retinopathy 11 12 *Samuel A. Mills, *Andrew I. Jobling, *Michael A. Dixon, Bang V. Bui, Kirstan A. Vessey, Joanna A. Phipps, 13 Ursula Greferath, Gene Venables, Vickie H.Y. Wong, Connie H.Y. Wong, Zheng He, Flora Hui, James C. 14 Young, Josh Tonc, Elena Ivanova, Botir T. Sagdullaev, Erica L. Fletcher 15 * Joint first authors 16 17 Corresponding author: 18 Prof. Erica L. Fletcher. Department of Anatomy & Neuroscience. The University of Melbourne, Grattan St, 19 Parkville 3010, Victoria, Australia. 20 Email: [email protected] ; Tel: +61-3-8344-3218; Fax: +61-3-9347-5219 21 22 This PDF file includes: 23 24 Supplementary text 25 Figures S1 to S10 26 Tables S1 to S7 27 Legends for Movies S1 to S2 28 SI References 29 30 Other supplementary materials for this manuscript include the following: 31 32 Movies S1 to S2 33 34 35 36 1 1 Supplementary Information Text 2 Materials and Methods 3 Microglial process movement on retinal vessels 4 Dark agouti rats were anaesthetized, injected intraperitoneally with rhodamine B (Sigma-Aldrich) to label blood 5 vessels and retinal explants established as described in the main text. Retinal microglia were labelled with Iba-1 6 and imaging performed on an inverted confocal microscope (Leica SP5). Baseline images were taken for 10 7 minutes, followed by the addition of PBS (10 minutes) and then either fractalkine or fractalkine + candesartan 8 (10 minutes) using concentrations outlined in the main text. -
Retinal Pigment Epithelium Protein of 65 Kda Gene
Molecular Vision 2013; 19:2312-2320 <http://www.molvis.org/molvis/v19/2312> © 2013 Molecular Vision Received 31 July 2013 | Accepted 14 November 2013 | Published 16 November 2013 Retinal pigment epithelium protein of 65 kDA gene-linked retinal degeneration is not modulated by chicken acidic leucine-rich epidermal growth factor-like domain containing brain protein/ Neuroglycan C/ chondroitin sulfate proteoglycan 5 Sandra Cottet,1,2 René Jüttner,3 Nathalie Voirol,1 Pierre Chambon,4 Fritz G. Rathjen,3 Daniel F. Schorderet,1,2,5 Pascal Escher1,2 1Institute for Research in Ophthalmology, Sion, Switzerland; 2Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland; 3Max-Delbrück-Centrum, Berlin, Germany; 4Institut de Génétique et de Biologie Moléculaire et Cellulaire, Collège de France, Strasbourg, France; 5EPFL-Ecole Polytechnique Fédérale, Lausanne, Switzerland Purpose: To analyze in vivo the function of chicken acidic leucine-rich epidermal growth factor-like domain containing brain protein/Neuroglycan C (gene symbol: Cspg5) during retinal degeneration in the Rpe65−/− mouse model of Leber congenital amaurosis. Methods: We resorted to mice with targeted deletions in the Cspg5 and retinal pigment epithelium protein of 65 kDa (Rpe65) genes (Cspg5−/−/Rpe65−/−). Cone degeneration was assessed with cone-specific peanut agglutinin staining. Tran- scriptional expression of rhodopsin (Rho), S-opsin (Opn1sw), M-opsin (Opn1mw), rod transducin α subunit (Gnat1), and cone transducin α subunit (Gnat2) genes was assessed with quantitative PCR from 2 weeks to 12 months. The retinal pigment epithelium (RPE) was analyzed at P14 with immunodetection of the retinol-binding protein membrane receptor Stra6. Results: No differences in the progression of retinal degeneration were observed between the Rpe65−/− and Cspg5−/−/ Rpe65−/− mice. -
Differential Regulation of Proteoglycan 4 Metabolism in Cartilage by IL-1A, IGF-I, and TGF-B1 T
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Osteoarthritis and Cartilage (2008) 16, 90e97 ª 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.joca.2007.05.009 International Cartilage Repair Society Differential regulation of proteoglycan 4 metabolism in cartilage by IL-1a, IGF-I, and TGF-b1 T. A. Schmidt Ph.D., N. S. Gastelum B.S., E. H. Han M.S., G. E. Nugent-Derfus Ph.D., B. L. Schumacher B.S. and R. L. Sah M.D., Sc.D.* Department of Bioengineering and Whitaker Institute of Biomedical Engineering, University of California-San Diego, La Jolla, CA 92093-0412, United States Summary Objectives: To determine (1) if interleukin-1 alpha (IL-1a), insulin like growth factor I (IGF-I), and transforming growth factor-beta 1 (TGF-b1) regulate proteoglycan 4 (PRG4) metabolism in articular cartilage, in terms of chondrocytes expressing PRG4 and PRG4 bound at the articular surface, and (2) if these features of cartilage PRG4 metabolism correlate with its secretion. Methods: Articular cartilage explants were harvested and cultured for 6 days with or without 10% fetal bovine serum (FBS), alone, or with the addition of 10 ng/ml IL-1a, 300 ng/ml IGF-I, or 10 ng/ml TGF-b1. PRG4 expression by chondrocytes in the cartilage disks was assessed by immunohistochemistry (IHC). PRG4 bound to the articular surface of disks was quantified by extraction and enzyme-linked immunosorbent assay (ELISA). PRG4 secreted into culture medium was quantified by ELISA and characterized by Western Blot. -
PRG4) in Modulating Osteoarthritic Synoviocyte Proliferation and Expression of Matrix Degrading Enzymes Ali Alquraini MCPHS University
Chapman University Chapman University Digital Commons Pharmacy Faculty Articles and Research School of Pharmacy 2017 The Autocrine Role of Proteoglycan-4 (PRG4) in Modulating Osteoarthritic Synoviocyte Proliferation and Expression of Matrix Degrading Enzymes Ali Alquraini MCPHS University Maha Jamal MCPHS University Ling Zhang Rhode Island Hospital Tannin Schmidt University of Calgary Gregory D. Jay Rhode Island Hospital FSeoe nelloxtw pa thige fors aaddndition addal aitutionhorsal works at: http://digitalcommons.chapman.edu/pharmacy_articles Part of the Amino Acids, Peptides, and Proteins Commons, Genetic Phenomena Commons, Other Chemicals and Drugs Commons, and the Pharmaceutical Preparations Commons Recommended Citation Alquraini A, Jamal M, Zhang L, Schmidt T, Jay GD, Elsaid KA. The uta ocrine role of proteoglycan-4 (PRG4) in modulating osteoarthritic synoviocyte proliferation and expression of matrix degrading enzymes. Arthritis Research & Therapy. 2017;19:89. doi:10.1186/s13075-017-1301-5. This Article is brought to you for free and open access by the School of Pharmacy at Chapman University Digital Commons. It has been accepted for inclusion in Pharmacy Faculty Articles and Research by an authorized administrator of Chapman University Digital Commons. For more information, please contact [email protected]. The Autocrine Role of Proteoglycan-4 (PRG4) in Modulating Osteoarthritic Synoviocyte Proliferation and Expression of Matrix Degrading Enzymes Comments This article was originally published in Arthritis Research & Therapy, volume 19, in 2017. DOI: 10.1186/ s13075-017-1301-5 Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 License. Copyright The uthora s Authors Ali Alquraini, Maha Jamal, Ling Zhang, Tannin Schmidt, Gregory D. Jay, and Khaled A.