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https://www.readbyqxmd.com/read/28816358/trpc3-mediated-ca-2-signals-as-a-promising-strategy-to-boost-therapeutic-angiogenesis-in-failing-hearts-the-role-of-autologous-endothelial-colony-forming-cells
#1
REVIEW
Francesco Moccia, Angela Lucariello, Germano Guerra
Endothelial progenitor cells (EPCs) are a sub-population of bone marrow-derived mononuclear cells that are released in circulation to restore damaged endothelium during its physiological turnover or rescue blood perfusion after an ischemic insult. Additionally, they may be mobilized from perivascular niches located within larger arteries' wall in response to hypoxic conditions. For this reason, EPCs have been regarded as an effective tool to promote revascularization and functional recovery of ischemic hearts, but clinical application failed to exploit the full potential of patients-derived cells...
August 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28807769/reduced-intensity-haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-for-solid-tumors-in-pediatric-and-young-adult-patients
#2
Nicolas J Llosa, Kenneth R Cooke, Allen Chen, Christopher Gamper, Orly Klein, Elias Zambidis, Brandon Luber, Gary Rosner, Nicholas Siegel, Mary Jo Holuba, Nancy Robey, Masanori Hayashi, Richard J Jones, Ephraim Fuchs, Matthias Holdhoff, David M Loeb, Heather J Symons
High risk, recurrent, or refractory solid tumors in pediatric, adolescent and young adult (AYA) patients have an extremely poor prognosis despite current intensive treatment regimens. We piloted an allogeneic bone marrow transplant (alloBMT) platform using a reduced intensity conditioning (RIC) and partially HLA-mismatched (haploidentical) related donors for this population of pediatric and AYA solid tumor patients. Sixteen patients received a fludarabine, cyclophosphamide (Cy), melphalan and low dose total body irradiation (TBI) RIC haploidentical BMT (haploBMT) followed by post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil (MMF) and sirolimus...
August 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28805792/immune-reconstitution-in-patients-with-acquired-severe-aplastic-anemia-after-haploidentical-stem-cell-transplantation
#3
X-Y Pei, X-Y Zhao, L-P Xu, Y Wang, X-H Zhang, Y-J Chang, X-J Huang
Immune recovery (IR) after haploidentical stem cell transplantation (haplo-SCT) in severe aplastic anemia (SAA) patients remains relatively unknown. In this study, we examined immune cell subset counts and immunoglobulins in 81 SAA patients from day 30 to day 365 after haplo-SCT. Simultaneously, we determined which factors influence IR and analyzed the effects of immune cell subsets on transplant outcomes. We found that: (i) The reconstitution of different immune cell subsets occurred at different rates after haplo-SCT...
August 14, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28803650/lipid-determination-in-bone-marrow-and-mineralized-bone-tissue-from-sample-preparation-to-improved-high-performance-thin-layer-and-liquid-chromatographic-approaches
#4
Alexandrine During
In view of their key roles in the bone physiology (e.g., in the biomineralization process) and their potential implication in bone pathologies, an approach to study lipids in situ is needed. The aim of the present paper is to propose an original procedure to characterize lipids in both bone marrow (BM) and mineralized tissue (MT) compartments, taking into consideration sample preparation, lipid extraction and analytical issues, when using small sample size (≤ 0.5g of rat femurs). The potential contamination of the MT by marrow lipids and the poor accessibility of certain lipids from the MT - two major issues in bone handling - were taking care, respectively by performing two cleaning steps after BM removal and by adding a demineralization step to the overall lipid extraction protocol...
August 3, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28800741/erythrocyte-depletion-from-bone-marrow-performance-evaluation-after-50-clinical-scale-depletions-with-spectra-optia-bmc
#5
Soo-Zin Kim-Wanner, Gesine Bug, Juliane Steinmann, Salem Ajib, Nadine Sorg, Carolin Poppe, Milica Bunos, Eva Wingenfeld, Christiane Hümmer, Beate Luxembourg, Erhard Seifried, Halvard Bonig
BACKGROUND: Red blood cell (RBC) depletion is a standard graft manipulation technique for ABO-incompatible bone marrow (BM) transplants. The BM processing module for Spectra Optia, "BMC", was previously introduced. We here report the largest series to date of routine quality data after performing 50 clinical-scale RBC-depletions. METHODS: Fifty successive RBC-depletions from autologous (n = 5) and allogeneic (n = 45) BM transplants were performed with the Spectra Optia BMC apheresis suite...
August 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28797779/long-term-outcomes-of-cord-blood-transplantation-from-an-hla-identical-sibling-for-patients-with-bone-marrow-failure-disorders-a-report-from-eurocord-cord-blood-committee-cbc-ctiwp-and-severe-aplastic-anemia-working-party-saawp-of-the-european-society-of-blood
#6
Simona Pagliuca, Régis Peffault de Latour, Fernanda Volt, Franco Locatelli, Marco Zecca, Jean-Hugues Dalle, Patrizia Comoli, Kim Vettenranta, Miguel Angel Diaz, Or Reuven, Yves Bertrand, Cristina Diaz de Heredia, Arnon Nagler, Ardeshir Ghavamzadeh, Sabina Sufliarska, Sarah Lawson, Chantal Kenzey, Vanderson Rocha, Carlo Dufour, Eliane Gluckman, Jakob Passweg, Annalisa Ruggeri
Cord blood transplantation (CBT) from HLA-identical sibling is an attractive option for patients with bone-marrow-failures syndromes (BMF), due to the low risk of graft-versus-host disease (GVHD) and the absence of risk to the donor. We analyzed outcomes of 117 patients with inherited or acquired BMF, who received CBT from a related HLA-identical donor in EBMT centers, between 1988 and 2014. Ninety-seven patients had inherited and 20 patients acquired BMF. Eighty-two patients received a single cord blood (CB) unit, whereas 35 patients received a combination of CB and bone marrow (BM) cells from the same donor...
August 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28796316/effects-of-tocilizumab-on-neutrophil-function-and-kinetics
#7
Laurence S C Lok, Neda Farahi, Jatinder K Juss, Chrystalla Loutsios, Chandra K Solanki, A Michael Peters, Francis Donaldson, Benjamin Porter-Brown, Edwin R Chilvers
BACKGROUND: Decreases in circulating neutrophils (polymorphonuclear leukocytes, PMNs) have been reported in patients treated with the anti-interleukin-6 receptor (IL-6R) antibody tocilizumab (TCZ); the mechanism for this is unclear. We hypothesize that TCZ reduces circulating neutrophils by affecting margination and / or bone marrow trafficking without affecting neutrophil function or apoptosis. MATERIALS AND METHODS: 18 healthy subjects were randomized to single intravenous dose of TCZ 8 mg/kg (n = 12) or placebo (n = 6) on day 0...
August 10, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28796258/loss-of-phd3-in-myeloid-cells-dampens-the-inflammatory-response-and-fibrosis-after-hind-limb-ischemia
#8
Angelika Beneke, Annemarie Guentsch, Annette Hillemann, Anke Zieseniss, Lija Swain, Dörthe M Katschinski
Macrophages are essential for the inflammatory response after an ischemic insult and thereby influence tissue recovery. For the oxygen sensing prolyl-4-hydroxylase domain enzyme (PHD) 2 a clear impact on the macrophage-mediated arteriogenic response after hind-limb ischemia has been demonstrated previously, which involves fine tuning a M2-like macrophage population. To analyze the role of PHD3 in macrophages, we performed hind-limb ischemia (ligation and excision of the femoral artery) in myeloid-specific PHD3 knockout mice (PHD3(-/-)) and analyzed the inflammatory cell invasion, reperfusion recovery and fibrosis in the ischemic muscle post-surgery...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28796194/a-murine-model-of-persistent-inflammation-immune-suppression-and-catabolism-syndrome
#9
Amanda M Pugh, Nicholas J Auteri, Holly S Goetzman, Charles C Caldwell, Vanessa Nomellini
Critically ill patients that survive sepsis can develop a Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS), which often leads to extended recovery periods and multiple complications. Here, we utilized a cecal ligation and puncture (CLP) method in mice with the goal of creating a model that concurrently displays all the characteristics of PICS. We observed that, after eight days, mice that survive the CLP develop persistent inflammation with significant myelopoiesis in the bone marrow and spleen...
August 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28794285/preventing-chemotherapy-induced-myelosuppression-by-repurposing-the-flt3-inhibitor-quizartinib
#10
Samuel J Taylor, Johanna M Duyvestyn, Samantha A Dagger, Emma J Dishington, Catherine A Rinaldi, Oliver M Dovey, George S Vassiliou, Carolyn S Grove, Wallace Y Langdon
We describe an approach to inhibit chemotherapy-induced myelosuppression. We found that short-term exposure of mice to the FLT3 inhibitor quizartinib induced the transient quiescence of multipotent progenitors (MPPs). This property of quizartinib conferred marked protection to MPPs in mice receiving fluorouracil or gemcitabine. The protection resulted in the rapid recovery of bone marrow and blood cellularity, thus preventing otherwise lethal myelosuppression. A treatment strategy involving quizartinib priming that protected wild-type bone marrow progenitors, but not leukemic cells, from fluorouracil provided a more effective treatment than conventional induction therapy in mouse models of acute myeloid leukemia...
August 9, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28783756/pkc-epsilon-deficiency-alters-progenitor-cell-populations-in-favor-of-megakaryopoiesis
#11
John C Kostyak, Elisabetta Liverani, Satya P Kunapuli
BACKGROUND: It has long been postulated that Protein Kinase C (PKC) is an important regulator of megakaryopoiesis. Recent contributions to the literature have outlined the functions of several individual PKC isoforms with regard to megakaryocyte differentiation and platelet production. However, the exact role of PKCε remains elusive. OBJECTIVE: To delineate the role of PKCε in megakaryopoiesis. APPROACH AND RESULTS: We used a PKCε knockout mouse model to examine the effect of PKCε deficiency on platelet mass, megakaryocyte mass, and bone marrow progenitor cell distribution...
2017: PloS One
https://www.readbyqxmd.com/read/28783657/plasmodium-products-persist-in-the-bone-marrow-and-promote-chronic-bone-loss
#12
Michelle S J Lee, Kenta Maruyama, Yukiko Fujita, Aki Konishi, Patrick M Lelliott, Sawako Itagaki, Toshihiro Horii, Jing-Wen Lin, Shahid M Khan, Etsushi Kuroda, Shizuo Akira, Ken J Ishii, Cevayir Coban
Although malaria is a life-threatening disease with severe complications, most people develop partial immunity and suffer from mild symptoms. However, incomplete recovery from infection causes chronic illness, and little is known of the potential outcomes of this chronicity. We found that malaria causes bone loss and growth retardation as a result of chronic bone inflammation induced by Plasmodium products. Acute malaria infection severely suppresses bone homeostasis, but sustained accumulation of Plasmodium products in the bone marrow niche induces MyD88-dependent inflammatory responses in osteoclast and osteoblast precursors, leading to increased RANKL expression and overstimulation of osteoclastogenesis, favoring bone resorption...
June 2, 2017: Science Immunology
https://www.readbyqxmd.com/read/28777945/long-term-engraftment-of-primary-bone-marrow-stromal-cells-repairs-niche-damage-and-improves-hematopoietic-stem-cell-transplantation
#13
Jean-Paul Abbuehl, Zuzana Tatarova, Werner Held, Joerg Huelsken
Hematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and adaptive immunity often causes fatal complications. HSC maintenance and lineage differentiation are supported by stromal niches, and we now find that bone marrow stroma cells (BMSCs) are severely and permanently damaged by the pre-conditioning irradiation required for efficient HSC transplantation. Using mouse models, we show that stromal insufficiency limits the number of donor-derived HSCs and B lymphopoiesis...
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28777523/transient-osteoporosis-of-the-hip-treated-with-hyperbaric-oxygen-therapy-a-case-series
#14
Kazuyoshi Yagishita, Tetsuya Jinno, Daisuke Koga, Tsuyoshi Kato, Mitsuhiro Enomoto, Tsuyoshi Kato, Takeshi Muneta, Atsushi Okawa
INTRODUCTION: Transient osteoporosis of the hip (TOH) is a self-limiting disorder characterized by bone marrow edema at the femoral head and neck. Patients report pain as moderate or severe at onset; pain gradually subsides at about six months (range four to 12 months). Differential diagnosis of the early stages of osteonecrosis of the femoral head (ONFH) is sometimes difficult. Because hyperbaric oxygen (HBO₂) therapy is effective for reduction of edema in soft tissue injury and early stages of ONFH, we hypothesized that HBO₂ could be effective in TOH for accelerated recovery...
November 2016: Undersea & Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Medical Society, Inc
https://www.readbyqxmd.com/read/28771086/exposure-to-low-dose-x-ray-radiation-alters-bone-progenitor-cells-and-bone-microarchitecture
#15
Florence Lima, Joshua M Swift, Elisabeth S Greene, Matthew R Allen, David A Cunningham, Leslie A Braby, Susan A Bloomfield
Exposure to high-dose ionizing radiation during medical treatment exerts well-documented deleterious effects on bone health, reducing bone density and contributing to bone growth retardation in young patients and spontaneous fracture in postmenopausal women. However, the majority of human radiation exposures occur in a much lower dose range than that used in the radiation oncology clinic. Furthermore, very few studies have examined the effects of low-dose ionizing radiation on bone integrity and results have been inconsistent...
August 3, 2017: Radiation Research
https://www.readbyqxmd.com/read/28761270/medicinal-plants-and-bone-healing
#16
REVIEW
Vibha Singh
Fracture is defined as complete or incomplete separation in the continuity of bone Fracture healing is a complex physiological process that involves the coordinated participation of hematopoietic and immune cells within bone marrow. It conjunction with vascular and skeletal cell precursors it also includes mesenchymal stem cells which are recruited from the circulation and the surrounding tissues. It is estimated that 80% of the population in developing countries still rely on the traditional herbal medicines...
January 2017: National Journal of Maxillofacial Surgery
https://www.readbyqxmd.com/read/28761170/intravenous-infusion-of-human-bone-marrow-mesenchymal-stromal-cells-promotes-functional-recovery-and-neuroplasticity-after-ischemic-stroke-in-mice
#17
Eliana Sammali, Claudia Alia, Gloria Vegliante, Valentina Colombo, Nadia Giordano, Francesca Pischiutta, Giorgio B Boncoraglio, Mario Barilani, Lorenza Lazzari, Matteo Caleo, Maria-Grazia De Simoni, Giuseppe Gaipa, Giuseppe Citerio, Elisa R Zanier
Transplantation of human bone marrow mesenchymal stromal cells (hBM-MSC) promotes functional recovery after stroke in animal models, but the mechanisms underlying these effects remain incompletely understood. We tested the efficacy of Good Manufacturing Practices (GMP) compliant hBM-MSC, injected intravenously 3.5 hours after injury in mice subjected to transient middle cerebral artery occlusion (tMCAo). We addressed whether hBM-MSC are efficacious and if this efficacy is associated with cortical circuit reorganization using neuroanatomical analysis of GABAergic neurons (parvalbumin; PV-positive cells) and perineuronal nets (PNN), a specialized extracellular matrix structure which acts as an inhibitor of neural plasticity...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760297/progress-in-myelodysplastic-syndromes-clinicopathologic-correlations-and-immune%C3%A2-checkpoints
#18
Juliana E Hidalgo-López, Rashmi Kanagal-Shamanna, Andrés E Quesada, Beenu Thakral, Zhihong Hu, Takayuki Mitsuhashi, Mariko Yabe, Guillermo Garcia-Manero, Carlos E Bueso-Ramos
BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal neoplasms characterized by ineffective hematopoiesis. Hypomethylating agent (HMA) therapy is one of the mainstays of MDS therapy. Failure of HMA therapy is related to poor outcome; hence, new therapeutic approaches are warranted in these patients. In MDS, the immune system has a pivotal role in modulation of hematopoiesis and clonal expansion. In neoplastic conditions, immune checkpoint (PD-1 and CTLA4 molecules) hide tumor cells from immune surveillance...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28757529/inhibition-of-adipogenesis-is-involved-in-the-protective-effects-of-1-25-dihydroxy-vitamin-d3-on-the-radiation-injured-bone-marrow-microenvironment-in-mice
#19
Zhao Zhou, Xiao-Yu Chen, Ai-Zhen Zhu, Cheng-Cheng Liu, Jin-Can Zhu, Ge-Xiu Liu
To explore the protective effects of 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) on the bone marrow microenvironment in mice after irradiation and the underlying molecular mechanisms, a total of 150 7-wk-old male BALB/c mice were randomly divided into a normal group, an irradiation (IR) group and an irradiation+1,25-(OH)2D3 (IR+VD3) group. The mice in the IR+VD3 group were treated with 6.0 Gy (60)Coγ rays, and 1,25-(OH)2D3 (dissolved in DMSO, 2.5 μg/kg) was administered once per day from 2 d before to 8 d after irradiation...
2017: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/28754835/in-vivo-functional-selection-identifies-cardiotrophin-1-as-a-cardiac-engraftment-factor-for-mesenchymal-stromal-cells
#20
Francesca Bortolotti, Giulia Ruozi, Antonella Falcione, Sara Doimo, Matteo Dal Ferro, Pierluigi Lesizza, Lorena Zentilin, Lawrence Banks, Serena Zacchigna, Mauro Giacca
Background -Transplantation of cells into the infarcted heart has significant potential to improve myocardial recovery; however, low efficacy of cell engraftment still limits therapeutic benefit. Here we describe a method for the unbiased, in vivo selection of cytokines that improve mesenchymal stromal cell (MSC) engraftment into the heart in both normal conditions and after myocardial infarction. Methods -An arrayed library of 80 secreted factors, including most of the currently known interleukins and chemokines, were individually cloned into adeno-associated viral (AAV) vectors...
July 28, 2017: Circulation
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