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Jennifer H Shepherd, Daniel Howard, Amie K Waller, Holly Rebecca Foster, Annett Muller, Thomas Moreau, Amanda L Evans, Meera Arumugam, Guénaëlle Bouët Chalon, Eleonora Vriend, Natalia Davidenko, Cedric Ghevaert, Serena M Best, Ruth E Cameron
Platelet transfusions are a key treatment option for a range of life threatening conditions including cancer, chemotherapy and surgery. Efficient ex vivo systems to generate donor independent platelets in clinically relevant numbers could provide a useful substitute. Large quantities of megakaryocytes (MKs) can be produced from human pluripotent stem cells, but in 2D culture the ratio of platelets harvested from MK cells has been limited and restricts production rate. The development of biomaterial cell supports that replicate vital hematopoietic micro-environment cues are one strategy that may increase in vitro platelet production rates from iPS derived Megakaryocyte cells...
August 8, 2018: Biomaterials
Jinlin Liu, Xiaocheng Luo, Wenjian Wang, Sujie Zheng, Huijun Lin, Juping Zeng, Mao Wu
To systemically analyze megakaryocytes in pleural and peritoneal fluids and their clinical significance. We retrospectively examined 10,846 pleural, peritoneal, and pericardial fluid samples obtained from 3 hospitals over a 20-year period. Megakaryocytes were observed in the pleural fluid samples from 7 patients and peritoneal fluid samples from 2 patients, and the incidence was 0.83%. The clinical diagnoses of these 9 patients included myeloproliferative disorders, trauma, and tumors. The serous effusions in all 9 patients were bloody, and the megakaryocytes could be associated with trauma, bone marrow pollution, extramedullary hematopoiesis, or cancer...
August 2018: Medicine (Baltimore)
Wei Liu, Bing Liu
OBJECTIVE: To establish a transplantation system for a trace amount of adult mouse bone marrow hematopoietic stem cells (HSCs). METHODS: The HSCs from bone marrow cells of GFP adult mouse were seperated by using marker combination ESLAM (CD45+ CD201+ CD150+ CD48- ) The goal cell population acquired by flow cytometry sorting were injected into lethally irradiated recipient mouse plus protective cells. And the peripheral blood cells from recipient mice tail veins at different time points were acquired to observe the reconstruction level and lineage differentiation...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Zhanshu Liu, Tonghua Mei
Immune thrombocytopenia (ITP) is the main pathogenesis of excessive platelet destruction and abnormal megakaryocyte apoptosis, however, the mechanism underlying this abnormality in megakaryocytes remains to be elucidated. Since autophagy and apoptosis are closely interrelated, it can be speculated that the abnormal apoptosis of ITP megakaryocytes is associated with autophagy. To test this hypothesis, a total of 14 patients with ITP and 23 healthy controls were recruited. MEG‑01 cell line was cultured in vitro, and morphological changes were observed by light microscopy, apoptosis was evaluated by flow cytometric analysis of Annexin V‑FITC/propidium iodide staining and western blot analysis of B‑cell lymphoma (Bcl)‑2, Bcl‑associated X protein (Bax), Beclin‑1 and cleaved caspase 3...
August 9, 2018: Molecular Medicine Reports
Taisuke Kanaji, My-Nuong Vo, Sachiko Kanaji, Alessandro Zarpellon, Ryan Shapiro, Yosuke Morodomi, Akinori Yuzuriha, Koji Eto, Rajesh Belani, Minh-Ha Do, Xiang-Lei Yang, Zaverio M Ruggeri, Paul Schimmel
New mechanisms behind blood cell formation continue to be uncovered, with therapeutic approaches for hematological diseases being of great interest. Here we report an enzyme in protein synthesis, known for cell-based activities beyond translation, is a factor inducing megakaryocyte-biased hematopoiesis, most likely under stress conditions. We show an activated form of tyrosyl-tRNA synthetase (YRSACT ), prepared either by rationally designed mutagenesis or alternative splicing, induces expansion of a previously unrecognized high-ploidy Sca-1+ megakaryocyte population capable of accelerating platelet replenishment after depletion...
August 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Amy S Northover, Aileen D Elliot, Sarah Keatley, Ziyuan Lim, Adriana Botero, Amanda Ash, Alan J Lymbery, Adrian F Wayne, Stephanie S Godfrey, R C Andrew Thompson
During monitoring of critically endangered woylie ( Bettongia penicillata ) populations within the south-west of Western Australia, an adult female woylie was euthanased after being found in extremely poor body condition with diffuse alopecia, debilitating skin lesions and severe ectoparasite infestation. Trypanosoma copemani G2 and Sarcocystis sp. were detected molecularly within tissue samples collected post-mortem. Potorostrongylus woyliei and Paraustrostrongylus sp. nematodes were present within the stomach and small intestine, respectively...
December 2018: International Journal for Parasitology. Parasites and Wildlife
Deborah Ingenhag, Sven Reister, Franziska Auer, Sanil Bhatia, Sarah Wildenhain, Daniel Picard, Marc Remke, Jessica I Hoell, Andreas Kloetgen, Dennis Sohn, Reiner U Jänicke, Gesine Koegler, Arndt Borkhardt, Julia Hauer
The homeobox gene HLXB9 encodes for the transcription factor HB9, which is essential for pancreatic as well as motor neuronal development. Beside its physiologic expression pattern, aberrant HB9 expression has been observed in several neoplasias. Especially in infant translocation t(7;12) acute myeloid leukemia aberrant HB9 expression is the only known molecular hallmark and assumed to be a key factor in leukemic transformation. However, up to now only poor functional data exist addressing the oncogenic potential of HB9 or its influence on hematopoiesis...
August 9, 2018: Haematologica
Kenji Kitajima, Mai Kanokoda, Marino Nakajima, Takahiko Hara
The generation of mouse hematopoietic stem cells from hemogenic endothelial cells (HECs) in the aorta/gonad/mesonephros region of developing embryos requires a zinc finger transcription factor Gata2. In the previous study, an enforced expression of Gata2 in vitro promoted the production of HECs from mesodermal cells differentiated from mouse embryonic stem cells (ESCs). Our research group has previously demonstrated that the enforced expression of Gata2 in ESC-derived HECs enhances erythroid and megakaryocyte differentiation and inhibits macrophage differentiation...
August 8, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Xudong Zhang, Jinqiang Wang, Zhaowei Chen, Quanyin Hu, Chao Wang, Junjie Yan, Gianpietro Dotti, Peng Huang, Zhen Gu
Radical surgery still represents the treatment choice for several malignancies. However, local and distant tumor relapses remain the major causes of treatment failure, indicating that a postsurgery consolidation treatment is necessary. Immunotherapy with checkpoint inhibitors has elicited impressive clinical responses in several types of human malignancies and may represent the ideal consolidation treatment after surgery. Here, we genetically engineered platelets from megakaryocyte (MK) progenitor cells to express the programmed cell death protein 1 (PD-1)...
July 31, 2018: Nano Letters
Zilong Li, Baoyu Chen, Wenhui Dong, Wenping Xu, Mingzi Song, Mingming Fang, Junli Guo, Yong Xu
Excessive reactive oxygen species (ROS) causes irreparable damages to cells and commit cells to programmed cell death or apoptosis. A panel of well-documented pro-apoptotic genes, including p53 apoptosis effector related to PMP-22 (PERP), are up-regulated and collectively mediate ROS induced apoptosis. The epigenetic mechanism whereby ROS stimulates PERP transcription, however, lacks in-depth characterization. Here we report that the transcriptional modulator megakaryocytic leukemia 1 (MKL1) is activated by H2 O2 treatment in skeletal muscle cells (C2C12)...
July 27, 2018: Biochimica et Biophysica Acta
Kyung-Hyun Lee, Du-Gyeong Han, Suhee Kim, Eun-Jin Choi, Kyoung-Seong Choi
BACKGROUND: Bovine viral diarrhea virus (BVDV) causes significant economic losses worldwide in the cattle industry through decrease in productive performance and immunosuppression of animals in herds. Recent studies conducted by our group showed that mice can be infected with BVDV-1 by the oral route. The purpose of this study was to assess the clinical signs, hematological changes, histopathological lesions in lymphoid tissues, and the distribution of the viral antigen after oral inoculation with a Korean noncytopathic (ncp) BVDV-2 field isolate in mice...
July 28, 2018: Virology Journal
Matthew M Klairmont, Deepthi Hoskoppal, Nour Yadak, John Kim Choi
Objectives: Immunohistochemistry (IHC) staining of core biopsy sections often plays an essential role in the diagnosis of acute megakaryoblastic leukemia (AMKL). The goal of this study was to define the relative sensitivities of commonly used stains for markers of megakaryocytic differentiation. Methods: The sensitivities of IHC stains for CD42b, CD61, and von Willebrand factor (vWF) were compared in 32 cases of pediatric AMKL. Results: The sensitivities of CD42b, CD61, and vWF were 90...
July 25, 2018: American Journal of Clinical Pathology
Prakrith Vijey, Benjamin Posorske, Kellie R Machlus
Megakaryocytes (MKs) are specialized precursor cells committed to producing and proliferating platelets. In a cytoskeletal-driven process, mature MKs generate platelets by releasing thin cytoplasmic extensions, named proplatelets, into the sinusoids. Due to knowledge gaps in this process and mounting clinical demand for non-donor-based platelet sources, investigators are successfully developing artificial culture systems to recreate the environment of platelet biogenesis. Nevertheless, drawbacks in current methods entail elaborate procedures for stem cell enrichment, extensive growth periods, low MK yield, and poor proplatelet production...
July 26, 2018: Platelets
Lisa J McReynolds, Katherine R Calvo, Steven M Holland
GATA2 deficiency is an immunodeficiency and bone marrow failure disorder caused by pathogenic variants in GATA2. It is inherited in an autosomal-dominant pattern or can be due to de novo sporadic germline mutation. Patients commonly have B-cell, dendritic cell, natural killer cell, and monocytopenias, and are predisposed to myelodysplastic syndrome, acute myeloid leukemia, and chronic myelomonocytic leukemia. Patients may suffer from disseminated human papilloma virus and mycobacterial infections, pulmonary alveolar proteinosis, and lymphedema...
August 2018: Hematology/oncology Clinics of North America
Isabella Massimi, Laura Alemanno, Maria L Guarino, Raffaella Guerriero, Luigi Frati, Luigi Biasucci, Fabio M Pulcinelli
Background: A mechanism involved in high on-aspirin treatment residual platelet reactivity is platelet multidrug resistance protein 4 (MRP4) overexpression. Aspirin enhances platelet MRP4 expression with a PPARα-dependent mechanism and reduces miR-21 expression that, in turn, downregulates PPARα expression. Objective: The aim of our study was to verify the relationship between miR-21 and MRP4-PPARα levels induced by aspirin treatment. Methods: We evaluated the changes in MRP4-PPARα, mRNA, MRP4 protein, and miR-21 expression induced by aspirin in: (i) in vitro-treated megakaryoblastic cell line (DAMI), (ii) primary megakaryocytes cultures and derived platelets, (iii) healthy volunteers' platelets treated with aspirin, and (iv) aspirinated patients (aspirin-treated patients) and in a control population (control)...
July 2018: Research and Practice in Thrombosis and Haemostasis
Tania Kamal, Taryn N Green, James I Hearn, Emma C Josefsson, Marie-Christine Morel-Kopp, Christopher M Ward, Matthew J During, Maggie L Kalev-Zylinska
<AbstractText Label="Background" NlmCategory="UNASSIGNED"> N -methyl-d-aspartate receptors (NMDARs) contribute calcium influx in megakaryocytic cells but their roles remain unclear; both pro- and anti-differentiating effects have been shown in different contexts. Objectives: The aim of this study was to clarify NMDAR contribution to megakaryocytic differentiation in both normal and leukemic cells. Methods: Meg-01, Set-2, and K-562 leukemic cell lines were differentiated using phorbol-12-myristate-13-acetate (PMA, 10 nmol L-1 ) or valproic acid (VPA, 500 μmol L-1 )...
January 2018: Research and Practice in Thrombosis and Haemostasis
Mansour S Aljabry, Shuaa Asiri, Tayseer Elsafi, Ghaleb Elyamany
Extramedullary hematopoiesis (EMH) is a presence of hematopoietic activity in the extramedullary sites. EMH can occur in both benign and malignant hematologic diseases. The liver and spleen are the most common sites, but may also occur infrequently at other sites. EMH often occurs in more than one site and quite rare in an isolated organ. In this study we describe an unusual case of generalized lymphadenopathy secondary to isolated extramedullary hematopoiesis as an initial manifestation of primary myelofibrosis...
May 14, 2018: Hematology Reports
Shelley M Herbrich, Sankaranarayanan Kannan, Riitta M Nolo, Marisa Hornbaker, Joya Chandra, Patrick A Zweidler-McKay
Tropomyosin-related kinase A (TRKA) translocations have oncogenic potential and have been found in rare cases of solid tumors. Accumulating evidence indicates that TRKA and its ligand, nerve growth factor (NGF), may play a role in normal hematopoiesis and may be deregulated in leukemogenesis. Here, we report a comprehensive evaluation of TRKA signaling in normal and leukemic cells. TRKA expression is highest in common myeloid progenitors and is overexpressed in core binding factor and megakaryocytic leukemias, especially Down syndrome-related AML...
July 10, 2018: Oncotarget
Maegan Capitano, Liang Zhao, Scott Cooper, Chelsea Thorsheim, Aae Suzuki, Xinxin Huang, Alexander L Dent, Michael S Marks, Charles S Abrams, Hal E Broxmeyer
We hypothesized that megakaryocyte (MK) phosphoinositide signaling mediated by phosphatidylinositol transfer protein(s) (Pitp) contributes to hematopoietic stem (HSC) and progenitor (HPC) cell regulation. Conditional knockout mice lacking Pitps specifically in MKs and platelets (pitpα-/- and pitpα-/- /β-/- ) bone marrow (BM) manifested decreased numbers of HSC, megakaryocyte-erythrocyte progenitors, and cycling HPC. Further, pitpα-/- /β-/- BM had significantly reduced engrafting capability in competitive transplantation and limiting dilution analysis...
July 24, 2018: Blood
Alanna C Green, Victoria Rudolph-Stringer, Lenny Straszkowski, Gavin Tjin, Blessing Crimeen-Irwin, Mannu Walia, T John Martin, Natalie A Sims, Louise E Purton
Retinoic acid receptor (RAR) signaling regulates bone structure and hematopoiesis through intrinsic and extrinsic mechanisms. This study aimed to establish how early in the osteoblast lineage loss of RARγ (Rarg) disrupts the bone marrow microenvironment. Bone structure was analyzed by micro-computed tomography (μCT) in Rarg-/- mice and mice with Rarg conditional deletion in Osterix-Cre-targeted osteoblast progenitors or Prrx1-Cre-targeted mesenchymal stem cells. Rarg-/- tibias exhibited less trabecular and cortical bone and impaired longitudinal and radial growth...
July 24, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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