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Inside this Issue: February

Posted By Connections Editor, Thursday, February 18, 2016

Hematopoietic niches, erythropoiesis and anemia of chronic infection
Ana Cordeiro Gomes, Maria Salomé Gomes


Anemia is a significant co-morbidity of chronic infections, as well as other inflammatory diseases. Anemia of chronic infection results from defective bone marrow erythropoiesis. Although the limitation of iron availability has been considered a key factor, the exact mechanisms underlying blockade in erythroid generation during infection are not fully understood. Erythropoiesis is a tightly regulated process that is very sensitive to environmental changes. During the last decade, the importance of the bone marrow hematopoietic niche has been progressively acknowledged.

How hematopoietic stem/progenitors and their niche sense and respond to infectious stress

Hiroshi Kobayashi, Toshio Suda, Keiyo Takubo


Hematopoietic stem/progenitor cells (HSPCs) play important roles in fighting systemic infection as they supply immune cells in a demand-adapted manner. Various mechanisms govern HSPC responses to infection, including cytokine signaling, niche function, and direct sensing of pathogen-derived molecules by HSPCs themselves. Here we review recent advances in our understanding of HSPC responses to infection and also consider newly identified STING-mediated machinery recognizing bacteria-derived cyclic dinucleotides.

Hematopoiesis “awakens”: Evolving technologies, the force behind them

Eugenia Flores-Figueroa, Marieke Essers, Teresa V. Bowman


Amid the beauty of the Kyoto countryside, leaders in the field of hematology met at the 44th annual International Society for Experimental Hematology (ISEH) meeting in late September 2015. Led by ISEH President Paul Frenette and President-Elect David Traver, the meeting covered many aspects of hematopoiesis with a focus on technology. At the meeting, it became clear that the future of hematology is being shaped by innovations in single-cell “omics” and imaging approaches that will provide answers to age-old questions on cellular identity.

Kinetics of lentiviral vector transduction in human CD34+ cells

Naoya Uchida, Rashidah Green, Josiah Ballantine, Luke P. Skala, Matthew M. Hsieh, John F. Tisdale


Cellular labile iron, which contains chelatable redox-active Fe2+, has been implicated in iron-mediated cellular toxicity leading to multiple organ dysfunction. Iron homeostasis is controlled by monocytes/macrophages through their iron recycling and storage capacities. Furthermore, iron sequestration by monocytes/macrophages is regulated by pro-inflammatory cytokines including interleukin-1, highlighting the importance of these cells in the crosstalk between inflammation and iron homeostasis. However, a role for cellular labile iron in monocyte/macrophage-mediated inflammatory responses has not been defined.

Activation of the NLRP3 inflammasome by cellular labile iron

Kyohei Nakamura, Toru Kawakami, Naoki Yamamoto, Miyu Tomizawa, Tohru Fujiwara, Tomonori Ishii, Hideo Harigae, Kouetsu Ogasawara


Cellular labile iron, which contains chelatable redox-active Fe2+, has been implicated in iron-mediated cellular toxicity leading to multiple organ dysfunction. Iron homeostasis is controlled by monocytes/macrophages through their iron recycling and storage capacities. Furthermore, iron sequestration by monocytes/macrophages is regulated by pro-inflammatory cytokines including interleukin-1, highlighting the importance of these cells in the crosstalk between inflammation and iron homeostasis. However, a role for cellular labile iron in monocyte/macrophage-mediated inflammatory responses has not been defined.

Effects and mechanism of arsenic trioxide in combination with rmhTRAIL in multiple myeloma

Hebing Zhou, Jinqing Li, Yuan Jian, Tingting Chen, Haiteng Deng, Juan Zhang, Hui Zeng, Zhijuan Shan, Wenming Chen


The anti-tumor potential of arsenic trioxide (ATO) and recombinant mutant human TRAIL (rmhTRAIL) has been confirmed in various kinds of tumors. However, the effects and mechanism of the two drugs in combination in multiple myeloma (MM) have not been established. In this study, we evaluated the proliferation inhibition and apoptosis induction effects of ATO and rmhTRAIL as single agents and in combination on the MM cell lines RPMI8226 and U266. Then, we used high-performance liquid chromatography and mass spectrometry to find differentially expressed proteins before and after drug treatment and to analyze the mechanism underlying the effect of ATO and rmhTRAIL on MM cells.

Bleeding the laboratory mouse: Not all methods are equal
Jonathan Hoggatt, Amber F. Hoggatt, Tiffany A. Tate, Jeffrey Fortman, Louis M. Pelus


The laboratory mouse is the model most frequently used in hematologic studies and assessment of blood parameters across a broad range of disciplines. Often, analysis of blood occurs in a nonterminal manner. However, the small body size of the mouse limits collection based on volume, frequency, and accessible sites. Commonly used sites in the mouse include the retro-orbital sinus, facial vein, tail vein, saphenous vein, and heart. The method of blood acquisition varies considerably across laboratories and is often not reported in detail.

Immunoregulatory effects on T lymphocytes by human mesenchymal stromal cells isolated from bone marrow, amniotic fluid, and placenta

Katia Mareschi, Sara Castiglia, Fiorella Sanavio, Deborah Rustichelli, Michela Muraro, Davide Defedele, Massimiliano Bergallo, Franca Fagioli


Mesenchymal stromal cells (MSCs) are a promising tool in cell therapies because of their multipotent, bystander, and immunomodulatory properties. Although bone marrow represents the main source of MSCs, there remains a need to identify a stem cell source that is safe and easily accessible and yields large numbers of cells without provoking debates over ethics. In this study, MSCs isolated from amniotic fluid and placenta were compared with bone marrow MSCs. Their immunomodulatory properties were studied in total activated T cells (peripheral blood mononuclear cells) stimulated with phytohemagglutinin (PHA-PBMCs).

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