Hematopoiesis News Volume 4.05 | Feb 12 2013

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    Hematopoiesis News 4.05 February 12, 2013
    Hematopoiesis News

         In this issue: Publications | ReviewsIndustry News | Policy News | Events | Jobs
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    TOP STORY
    FOXO3A Directs a Protective Autophagy Program in Hematopoietic Stem Cells
    Scientists identified autophagy as an essential mechanism protecting hematopoietic stem cells (HSCs) from metabolic stress. They showed that mouse HSCs, in contrast to their short-lived myeloid progeny, robustly induce autophagy after ex vivo cytokine withdrawal and in vivo calorie restriction. [Nature] Abstract

    Free Wallchart: Identification Of Colonies Derived From Mouse Hematopoietic Progenitors

    PUBLICATIONS (Ranked by impact factor of the journal)

    LABORATORY RESEARCH

    Growth Factor Independence 1 Antagonizes a p53-Induced DNA Damage Response Pathway in Lymphoblastic Leukemia
    Since oncogenic signaling activates a p53-dependent DNA damage response and apoptosis, leukemic cells must devise appropriate countermeasures. Researchers showed that growth factor independence 1 (Gfi1) can serve such a function because Gfi1 ablation exacerbates p53 responses and lowers the threshold for p53-induced cell death. [Cancer Cell] Abstract | Press Release

    Sustained PU.1 Levels Balance Cell-Cycle Regulators to Prevent Exhaustion of Adult Hematopoietic Stem Cells
    To provide a lifelong supply of blood cells, hematopoietic stem cells need to carefully balance both self-renewing cell divisions and quiescence. Although several regulators that control this mechanism have been identified, the authors demonstrated that the transcription factor PU.1 acts upstream of these regulators. [Mol Cell] Abstract

    miR-21 Mediates Hematopoietic Suppression in MDS by Activating TGF-β Signaling
    Scientists observed that SMAD7, a negative regulator of TGF-β receptor-I kinase, is markedly reduced in myelodysplastic syndromes (MDS), and leads to ineffective hematopoiesis by overactivation of TGF-β signaling. To determine the cause of SMAD7 reduction in MDS, they analyzed the 3’UTR of the gene and determined that it contains a highly conserved putative binding site for microRNA (miR)-21. [Blood] Abstract

    Transgene-Free iPSCs Generated from Small Volume Peripheral Blood Non-Mobilized CD34+ Cells
    Researchers report a method for deriving induced pluripotent stem cells (iPSCs) from peripheral blood hematopoietic stem cells (HSCs) using immunobead purification and 2-4 day culture to enrich CD34+ HSCs, followed by reprogramming with loxP-flanked polycistronic STEMCCA-loxP lentivector; or with Sendai vectors. [Blood] Abstract

    Hematopoietic Stem Cell and Progenitor Cell Mechanisms in Myelodysplastic Syndromes
    The authors transplanted purified human hematopoietic stem cells (HSCs) from myelodysplastic syndromes (MDS) samples into immunodeficient mice and show that HSCs are the disease-initiating cells in MDS. [Proc Natl Acad Sci USA] Abstract

    Chronic TLR Signaling Impairs the Long-Term Repopulating Potential of Hematopoietic Stem Cells of Wild Type but Not Id1 Deficient Mice
    To determine the effects of LPS treatment on hematopoietic stem cell function and to evaluate the significance of Id1 expression, the authors assessed the repopulating potential of wild type and Id1 deficient mice, which were subjected to a 30 day regimen of LPS treatment. [PLoS One] Full Article

    CLINICAL RESEARCH

    Treatment Reduction for Children and Young Adults with Low-Risk Acute Lymphoblastic Leukemia Defined by Minimal Residual Disease (UKALL 2003): A Randomized Controlled Trial
    Minimal residual disease (MRD) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukemia during remission. Researchers assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification. [Lancet Oncol] Abstract

    H-Y Antigen-Binding B Cells Develop in Male Recipients of Female Hematopoietic Cells and Associate with Chronic Graft vs. Host Disease
    The authors previously showed that IgG allo-antibodies recognize Y chromosome-encoded proteins (H-Y) and a dominant H-Y epitope, DEAD box protein (DBY-2) detectable 6-12 months after transplant in male patients who receive grafts from female donors (F→M) in hematopoietic cell transplantation (HCT). Here they present FACS studies of peripheral blood mononuclear cells collected 6 months after transplant showing that 16 of 28 F→M HCT patients have circulating donor B cells that express B-cell receptor specific for DBY-2. [Proc Natl Acad Sci USA] Abstract | Press Release

    Infusion of Megakaryocytic Progenitor Products Generated from Cord Blood Hematopoietic Stem/Progenitor Cells: Results of the Phase I Study
    Megakaryocytic progenitor cells (MPs) were produced and characterized from cord blood mononuclear cells under a serum free medium with cytokines. Researchers investigated the feasibility of expansion and infusion of cord blood-derived MPs in 24 patients with advanced hematological malignancies. [PLoS One]
    Full Article

    Tech Bulletin: Expansion Of Hematopoietic Stem And Progenitor Cells

    REVIEWS
    Wnt Signaling in Normal and Malignant Hematopoiesis
    The authors trace the emerging role of Wnt signaling as a critical regulator of distinct aspects of self-renewal and differentiation, its contribution to the maintenance of homeostasis and regeneration, and how the pathway can be hijacked to promote leukemia development. [Cold Spring Harb Perspect Biol] Abstract

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    INDUSTRY NEWS

    Regen BioPharma Files Investigational New Drug (IND) Application with FDA on HemaXellerate I™ Stem Cell Drug for Aplastic Anemia
    Regen BioPharma, a wholly-owned subsidiary of Bio-Matrix Scientific Group Inc., announced filing of an IND application with the FDA to initiate clinical trials assessing the company’s HemaXellerate I™ stem cell drug in patients with drug-refractory aplastic anemia. [Marketwire] Press Release

    Northwestern Medicine Researchers Investigate Stem Cell Therapy for Stroke
    Northwestern Medicine® researchers are investigating a novel stem cell therapy, known as SB623, that may hold the key to improving motor function following a disabling stroke. While the study’s primary purpose is to examine the safety of SB623 stem cells, researchers will also seek to determine if the cells are effective in improving stroke symptoms. [Northwestern Memorial Hospital] Press Release

    Gamida Cell’s StemEx® Achieves Primary Endpoint in Phase II/III Clinical Study
    Gamida Cell announced that its flagship product, StemEx, reached its primary endpoint of improving overall survival in a Phase II/III study which compared the use of StemEx as part of a transplantation regimen to historical controls in the treatment of patients with hematological malignancies such as leukemia and lymphoma. [Gamida Cell] Press Release

    POLICY NEWS

    National Institutes of Health (United States)

    Food and Drug Administration (United States)
     
    Center for Biologics Evaluation and Research (United States)
     
    European Medicines Agency (European Union)

    Medicines and Healthcare Products Regulatory Agency (United Kingdom)

    Therapeutic Goods Administration (Australia)

    EVENTS

    NEW Clinical Translation of Stem Cells 2013
    April 22-23, 2013
    Palm Springs, United States

    NEW Stem Cells & Cell Therapy Summit
    September 5-6, 2013
    London, United Kingdom

    Visit our events page to see a complete list of events in the hematopoietic community.

    JOB OPPORTUNITIES

    Postdoctoral Position – Gene Regulation in the Hematopoietic and Immune Systems (Lund University)

    Postdoctoral Positions – Stem Cell Biology (Children’s Hospital Oakland Research Institute)

    Postdoctoral Position – Hematopoietic and Malignant Stem Cells (Istanbul University)

    Postdoctoral Position – Stem Cell Biology (Washington University of Medicine)

    Postdoctoral Research Associate – Stem Cell Biology and Epigenetics (University of Wisconsin)

    Postdoctoral Position – Gene Expression and Regulation of Stem Cells (University of Texas at Houston)

    Postdoctoral Position – Myeloproliferative Neoplasms (Mount Sinai Medical Center)

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