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I C Haznedaroglu, U Y Malkan
The existence of a local renin-angiotensin system (RAS) specific to the hematopoietic bone marrow (BM) microenvironment had been proposed two decades ago. Most of the RAS molecules including ACE, ACE2, AGT, AGTR1, AGTR2, AKR1C4, AKR1D1, ANPEP, ATP6AP2, CMA1, CPA3, CTSA, CTSD, CTSG, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, DPP3, EGFR, ENPEP, GPER, HSD11B1, HSD11B2, IGF2R, KLK1, LNPEP, MAS1, MME, NR3C1, NR3C2, PREP, REN, RNPEP, and THOP1 are locally present in the BM microenvironment. Local BM RAS peptides control the hematopoietic niche, myelopoiesis, erythropoiesis, thrombopoiesis and the development of other cellular lineages...
October 2016: European Review for Medical and Pharmacological Sciences
K B Skowron, S P Pitroda, J P Namm, O Balogun, M A Beckett, M L Zenner, O Fayanju, X Huang, C Fernandez, W Zheng, G Qiao, R Chin, S J Kron, N N Khodarev, M C Posner, G D Steinberg, R R Weichselbaum
Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation...
October 24, 2016: Scientific Reports
Worawut Choeyprasert, Suradej Hongeng, Usanarat Anurathapan, Samart Pakakasama
Bacteremia during neutropenic episodes is a cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). We have used oral ciprofloxacin and penicillin V, from the start of the conditioning regimen until engraftment, for the prophylaxis of bacterial infection. The objective of this study was to retrospectively analyze the prevalence of and risk factors for breakthrough bacteremia during neutropenic episodes in autologous and allogeneic HSCT patients. There were 215 patients enrolled, with a median age of 8...
October 22, 2016: International Journal of Hematology
Changcheng Zheng, Baolin Tang, Xiaoyu Zhu, Xuhan Zhang, Lei Zhang, Liangquan Geng, Huilan Liu, Zimin Sun
The aim of this study is to investigate the impact of pre-engraftment bloodstream infections (BSIs) on the outcomes in acute leukemia patients undergoing myeloablative cord blood transplantation (CBT). A total of 226 acute leukemia patients who received unrelated CBT were enrolled in this study, and all these patients received an intensified myeloablative conditioning without ATG. Pre-engraftment BSIs occurred in 72 patients (31.9 %), and the median time of onset was 4.5 days after cord blood infusion, BSIs of gram-negative bacilli, and gram-positive cocci comprised of 63...
October 22, 2016: Annals of Hematology
Shanzheng Lu, Ganggang Shi, Xiaoxi Xu, Grace Wang, Xu Lan, Peng Sun, Xiang Li, Baoren Zhang, Xiangying Gu, Thomas E Ichim, Hao Wang
BACKGROUND: The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI). METHODS: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4...
October 22, 2016: Journal of Translational Medicine
Jasmin Nurković, Ivan Zaletel, Selmina Nurković, Šefćet Hajrović, Fahrudin Mustafić, Jovan Isma, Aleksandra Jurišić Škevin, Vesna Grbović, Milica Kovačević Filipović, Zana Dolićanin
In recent years, electromagnetic field (EMF) and low-level laser (LLL) have been found to affect various biological processes, the growth and proliferation of cells, and especially that of stem cells. The aim of this study was to investigate the effects of EMF and LLL on proliferation of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and thus to examine the impact of these therapeutic physical modalities on stem cell engraftment. hAT-MSCs were isolated from subcutaneous adipose tissue of six persons ranging in age from 21 to 56 years...
October 21, 2016: Lasers in Medical Science
Darwin J Prockop
From the outset, it was apparent that developing new therapies with mesenchymal stem/stromal cells (MSCs) was not a simple or easy task. Among the earliest experiments was administration of MSCs from normal mice to transgenic mice that developed brittle bones because they expressed a mutated gene for type 1 collagen isolated from a patient with osteogenesis imperfecta. The results prompted a clinical trial of MSCs in patients with severe osteogenesis imperfecta. Subsequent work by large numbers of scientists and clinicians has established that, with minor exceptions, MSCs do not engraft or differentiate to a large extent in vivo...
October 18, 2016: Cytotherapy
Serdar Sivgin, Sinan Nazlim, Gokmen Zararsiz, Osman Baspinar, Leylagul Kaynar, Kemal Deniz, Mustafa Cetin, Ali Unal, Bulent Eser
BACKGROUND: Iron overload is one of the most significant problems as a leading cause of death in patients with leukemia and those who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). METHODS: In the current study, we retrospectively evaluated the bone marrow iron scores (BMIS) in patients who underwent alloHSCT (n = 125). The first available bone marrow biopsy specimens prior to the alloHSCT procedure or date of hospitalization (control group) were assessed in a blinded fashion using a standardized scoring system...
October 2016: Clinical Lymphoma, Myeloma & Leukemia
L Faivre, M Chaussard, L Vercellino, V Vanneaux, B Hosten, K Teixera, V Parietti, P Merlet, L Sarda-Mantel, N Rizzo-Padoin, J Larghero
PURPOSE OF THE STUDY: After transplantation, cord blood (CB) hematopoietic stem and progenitor cells (HSPCs) are able to home to the bone marrow niche and to reconstitute the hematopoietic system. PET-CT imaging may be a useful method to monitor this parameter in different conditions. The aim of our study was to set up an efficient method for HSPC radiolabelling with [(18)F] fluorodeoxyglucose ((18)F-FDG) and to follow early HSPC homing through PET-CT in mice. MATERIALS AND METHODS: Purified CB HSPCs were radiolabelled with (18)F-FDG at 37° C with various conditions of cell concentration, incubation time and radioactivity concentration in order to define the in vitro condition that allows both sufficient (18)F-FDG uptake to get high quality PET imaging, and preservation of HSPC viability and functional properties during 3h after radiolabelling...
July 2016: Current Research in Translational Medicine
Constanze Hantel, Igor Shapiro, Giada Poli, Costanza Chiapponi, Martin Bidlingmaier, Martin Reincke, Michaela Luconi, Sara Jung, Felix Beuschlein
In recent years it has been recognized that clinical translation of novel therapeutic strategies for patients with adrenocortical carcinoma (ACC) often fails. These disappointing results indicate that the currently utilized tumor models only poorly reflect relevant pathophysiology and, thereby, do not predict clinical applicability of novel pharmacological approaches. However, also the development of new preclinical ACC models has remained a challenge with only one human cell line (NCI-H295R) and one recently established human pediatric xenograft model (SJ-ACC3) being available for this highly heterogeneous malignancy...
October 15, 2016: Oncotarget
Hannah K Choe, Usama Gergis, Sebastian A Mayer, Himanshu Nagar, Adrienne A Phillips, Tsiporah B Shore, Michael J Smith, Koen van Besien
BACKGROUND: Preliminary evidence indicates that the addition of low dose TBI (2-4 Gy) to reduced intensity conditioning may reduce the rate of relapse in allogeneic stem cell transplants. In very high risk patients receiving combination haploidentical-single unit cord blood transplants, we have added 4 Gy TBI to the widely used fludarabine, melphalan conditioning regimen, in hopes of reducing relapse and decreasing graft rejection. METHODS: We retrospectively reviewed the posttransplant outcomes of patients who underwent haplo-cord SCT between May 2013 and March 2015 and who received fludarabine 30mg/m2 D-7 to -3, melphalan 140mg/m2 D-2, and 2 Gy TBI D-4 and -3...
October 19, 2016: Transplantation
Nirali N Shah, Theresa M Watson, Bonnie Yates, David J Liewehr, Seth M Steinberg, David Jacobsohn, Terry J Fry
BACKGROUND: Diagnosis of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) can be a challenge due to the systemic presentation and alternative etiologies. With a goal of establishing biomarkers to more accurately distinguish ES, we prospectively analyzed levels of cytokines during HSCT. PROCEDURES: We performed a prospective study of children ≤21 years who underwent allogeneic HSCT. Blood samples for interleukin (IL)-6, IL-8, IL-10, IL-1b, IL-12p70, interferon-γ, tumor necrosis factor alpha (TNF-α) and procalcitonin were obtained from each subject prior to conditioning, at day 0, and then biweekly through engraftment and at days 30, 60 and 100...
October 20, 2016: Pediatric Blood & Cancer
Christina Susanne Mullins, Stephanie Bock, Mathias Krohn, Michael Linnebacher
Human tumor in vivo cancer models raised in immunodeficient mice, the so-called patient-derived xenografts, are increasingly in use in preclinical development and evaluation of novel drug candidates including HDAC inhibitors. Here, we describe the techniques needed to generate novel patient-derived xenografts. The focus lies on vitally frozen tumor biopsies as starting material. First, the preparative steps on the animals, followed by the engraftment procedure itself, the tumor growth surveillance, the explantation procedure, and finally the handling of obtained xenograft tissues are described step by step...
2017: Methods in Molecular Biology
Laurel L Ballantyne, Yuan Yan Sin, Osama Y Al-Dirbashi, Xinzhi Li, David J Hurlbut, Colin D Funk
Arginase-1 (Arg1) converts arginine to urea and ornithine in the distal step of the urea cycle in liver. We previously generated a tamoxifen-inducible Arg1 deficient mouse model (Arg1-Cre) that disrupts Arg1 expression throughout the whole body and leads to lethality ≈ 2 weeks after gene disruption. Here, we evaluate if liver-selective Arg1 loss is sufficient to recapitulate the phenotype observed in global Arg1 knockout mice, as well as to gauge the effectiveness of gene delivery or hepatocyte transplantation to rescue the phenotype...
December 2016: Molecular Genetics and Metabolism Reports
Florent Elefteriou
The bone marrow microenvironment is characterized by its multicellular nature, and perhaps less obviously by the high mobility of multiple transient and stationary cell lineages present in this environment. The trafficking of hematopoietic and mesenchymal cells between the bone marrow and blood compartments is regulated by a number of bone marrow-derived factors. It is suspected that transformed metastatic cells "hijack" these processes to engraft into the skeleton and eventually cause the skeletal complications associated with metastatic disease...
September 2016: Journal of Bone Oncology
Shaun S Tan, Zhi Yang Ng, Weiqing Zhan, Warren Rozen
Autologous fat grafting is commonly utilised to reconstruct soft tissue defects caused by ageing, trauma, chronic wounds and cancer resection. The benefits of fat grafting are minimal donor site morbidity and ease of availability through liposuction or lipectomy. Nonetheless, survival and longevity of fat grafts remain poor post-engraftment. Various methods to enhance fat graft survival are currently under investigation and its stem cell constituents are of particular interest. Cell-assisted lipotransfer refers to the addition of adipose-derived stem cell (ASC) rich component of stromal vascular fraction to lipoaspirate, the results of which have proven promising...
July 2016: Journal of Cutaneous and Aesthetic Surgery
Omar S Aljitawi, Soumen Paul, Avishek Ganguly, Tara L Lin, Sid Ganguly, George Vielhauer, Maegan L Capitano, Amy Cantelina, Brea Lipe, Jonathan D Mahnken, Amanda Wise, Abigale Berry, Anurag K Singh, Leyla Shune, Christopher Lominska, Sunil Abhyankar, Dennis Allin, Mary Laughlin, Joseph P McGuirk, Hal E Broxmeyer
Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed in order to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34(+) cells...
October 19, 2016: Blood
Elizabeth M Todd, Julie Y Zhou, Taylor P Szasz, Lauren E Deady, June A D'Angelo, Matthew D Cheung, Alfred H J Kim, Sharon Celeste Morley
Alveolar macrophages are lung-resident sentinel cells that develop perinatally and protect against pulmonary infection. Molecular mechanisms controlling alveolar macrophage generation have not been fully defined. Here we show that the actin-bundling protein L-plastin (LPL) is required for the perinatal development of alveolar macrophages. Mice expressing a conditional allele of LPL (CD11c.Cre(pos)-LPL(fl/fl)) exhibited significant reductions in alveolar macrophages and failed to effectively clear pulmonary pneumococcal infection, showing that immunodeficiency results from reduced alveolar macrophage numbers...
October 6, 2016: Blood
Ashley I Beyer, Marcus O Muench
Immunodeficient mice play a critical role in hematology research as in vivo models of hematopoiesis and immunology. Multiple strains have been developed, but hematopoietic stem cell engraftment and immune reconstitution have not been methodically compared among them. Four mouse strains were transplanted with human fetal bone marrow or adult peripheral blood CD34+ cells: NSG, NSG-3GS, hSCF-Tg-NSG and hSIRPα-DKO. Hematopoietic engraftment in the bone marrow, blood, spleen and liver was evaluated by flow cytometry 12 weeks after transplant...
October 19, 2016: Stem Cells and Development
Na Kyung Lee, Hyeong Seop Kim, Dongkyeom Yoo, Jung Won Hwang, Soo Jin Choi, Wonil Oh, Jong Wook Chang, Duk L Na
The success of stem cell therapy is highly dependent on accurate delivery of stem cells to the target site of interest. Possible ways to track the distribution of MSCs in vivo include the use of reporter genes or nanoparticles. The U.S. Food and Drug Administration (FDA) has approved ferumoxytol (Feraheme® [USA], Rienso® [UK]) as a treatment for iron deficiency anemia. Ferumoxytol is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) that has recently been used to track the fate of transplanted cells using magnetic resonance imaging (MRI)...
October 18, 2016: Stem Cell Reviews
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