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Sample records for blood derived mesenchymal-like

  1. Roles of db-cAMP, IBMX and RA in aspects of neural differentiation of cord blood derived mesenchymal-like stem cells.

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    Murni Tio

    Full Text Available Mesenchymal stem cells (MSCs have multilineage differentiation potential which includes cell lineages of the central nervous system; hence MSCs might be useful in the treatment of neurodegenerative diseases such as Parkinson's disease. Although mesenchymal stem cells have been shown to differentiate into the neural lineage, there is still little knowledge about the underlying mechanisms of differentiation particularly towards specialized neurons such as dopaminergic neurons. Here, we show that MSCs derived from human umbilical cord blood (MSC(hUCBs are capable of expressing tyrosine hydroxylase (TH and Nurr1, markers typically associated with DA neurons. We also found differential phosphorylation of TH isoforms indicating the presence of post-translational mechanisms possibly activating and modifying TH in MSC(hUCB. Furthermore, functional dissection of components in the differentiation medium revealed that dibutyryl-cAMP (db-cAMP, 3-isobutyl-1-methylxanthine (IBMX and retinoic acid (RA are involved in the regulation of Nurr1 and Neurofilament-L expression as well as in the differential phosphorylation of TH. We also demonstrate a possible inhibitory role of the protein kinase A signaling pathway in the phosphorylation of specific TH isoforms.

  2. Generation, Characterization, and Multilineage Potency of Mesenchymal-Like Progenitors Derived from Equine Induced Pluripotent Stem Cells.

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    Lepage, Sarah I; Nagy, Kristina; Sung, Hoon-Ki; Kandel, Rita A; Nagy, Andras; Koch, Thomas G

    2016-01-01

    Multipotent mesenchymal stromal cells (MSCs) are more and more frequently used to treat orthopedic injuries in horses. However, these cells are limited in their expandability and differentiation capacity. Recently, the first equine-induced pluripotent stem cell (iPSC) lines were reported by us [ 1 ]. In vitro differentiation of iPSCs into MSC-like cells is an attractive alternative to using MSCs derived from other sources, as a much larger quantity of patient-specific cells with broad differentiation potential could be generated. However, the differentiation capacity of iPSCs to MSCs and the potential for use in tissue engineering have yet to be explored. In this study, equine iPSCs were induced to differentiate into an MSC-like population. Upon induction, the iPSCs changed morphology toward spindle-shaped cells similar to MSCs. The ensuing iPSC-MSCs exhibited downregulation of pluripotency-associated genes and an upregulation of MSC-associated genes. In addition, the cells expressed the same surface markers as MSCs derived from equine umbilical cord blood. We then assessed the multilineage differentiation potential of iPSC-MSCs. Although chondrogenesis was not achieved after induction with transforming growth factor-beta 3 (TGFβ3) and/or bone morphogenic protein 4 (BMP-4) in 3D pellet culture, mineralization characteristic of osteogenesis and lipid droplet accumulation characteristic of adipogenesis were observed after chemical induction. We demonstrate a protocol for the derivation of MSC-like progenitor populations from equine iPS cells.

  3. Ophthalmic use of blood-derived products.

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    Nugent, Ryan B; Lee, Graham A

    2015-01-01

    There is a wide spectrum of blood-derived products that have been used in many different medical and surgical specialties with success. Blood-derived products for clinical use can be extracted from autologous or allogeneic specimens of blood, but recombinant products are also commonly used. A number of blood derivatives have been used for a wide range of ocular conditions, from the ocular surface to the retina. With stringent preparation guidelines, the potential risk of transmission of blood-borne diseases is minimized. We review blood-derived products and how they are improving the management of ocular disease.

  4. Adult human nasal mesenchymal-like stem cells restore cochlear spiral ganglion neurons after experimental lesion.

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    Bas, Esperanza; Van De Water, Thomas R; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M; Goldstein, Bradley J

    2014-03-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic.

  5. Human placenta-derived stromal cells decrease inflammation, placental injury and blood pressure in hypertensive pregnant mice.

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    Chatterjee, Piyali; Chiasson, Valorie L; Pinzur, Lena; Raveh, Shani; Abraham, Eytan; Jones, Kathleen A; Bounds, Kelsey R; Ofir, Racheli; Flaishon, Liat; Chajut, Ayelet; Mitchell, Brett M

    2016-04-01

    Pre-eclampsia, the development of hypertension and proteinuria or end-organ damage during pregnancy, is a leading cause of both maternal and fetal morbidity and mortality, and there are no effective clinical treatments for pre-eclampsia aside from delivery. The development of pre-eclampsia is characterized by maladaptation of the maternal immune system, excessive inflammation and endothelial dysfunction. We have reported that detection of extracellular RNA by the Toll-like receptors (TLRs) 3 and 7 is a key initiating signal that contributes to the development of pre-eclampsia. PLacental eXpanded (PLX-PAD) cells are human placenta-derived, mesenchymal-like, adherent stromal cells that have anti-inflammatory, proangiogenic, cytoprotective and regenerative properties, secondary to paracrine secretion of various molecules in response to environmental stimulation. We hypothesized that PLX-PAD cells would reduce the associated inflammation and tissue damage and lower blood pressure in mice with pre-eclampsia induced by TLR3 or TLR7 activation. Injection of PLX-PAD cells on gestational day 14 significantly decreased systolic blood pressure by day 17 in TLR3-induced and TLR7-induced hypertensive mice (TLR3 144-111 mmHg; TLR7 145-106 mmHg; both Pinflammation and placental injury, increased markedly in both groups of TLR-induced hypertensive mice, were reduced by PLX-PAD cells. Importantly, PLX-PAD cell therapy had no effects on these measures in pregnant control mice or on the fetuses. These data demonstrate that PLX-PAD cell therapy can safely reverse pre-eclampsia-like features during pregnancy and have a potential therapeutic role in pre-eclampsia treatment.

  6. Radiohalogenated thienylethylamine derivatives for evaluating local cerebral blood flow

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    Goodman, Mark M.; Knapp, Jr., Furn F.

    1990-01-01

    Radiopharmaceuticals useful in brain imaging comprising radiohalogenated thienylethylamine derivatives. The compounds are 5-halo-thiophene-2-isopropyl amines able to cross the blood-brain barrier and be retained for a sufficient length of time to allow the evaluation or regional blood flow by radioimaging of the brain.

  7. The treatment of neurodegenerative disorders using umbilical cord blood and menstrual blood-derived stem cells.

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    Sanberg, Paul R; Eve, David J; Willing, Alison E; Garbuzova-Davis, Svitlana; Tan, Jun; Sanberg, Cyndy D; Allickson, Julie G; Cruz, L Eduardo; Borlongan, Cesar V

    2011-01-01

    Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual blood-derived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.

  8. Blood-derived DNA methylation markers of cancer risk.

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    Marsit, Carmen; Christensen, Brock

    2013-01-01

    The importance of somatic epigenetic alterations in tissues targeted for carcinogenesis is now well recognized and considered a key molecular step in the development of a tumor. Particularly, alteration of gene-specific and genomic DNA methylation has been extensively characterized in tumors, and has become an attractive biomarker of risk due to its specificity and stability in human samples. It also is clear that tumors do not develop as isolated phenomenon in their target tissue, but instead result from altered processes affecting not only the surrounding cells and tissues, but other organ systems, including the immune system. Thus, alterations to DNA methylation profiles detectable in peripheral blood may be useful not only in understanding the carcinogenic process and response to environmental insults, but can also provide critical insights in a systems biological view of tumorigenesis. Research to date has generally focused on how environmental exposures alter genomic DNA methylation content in peripheral blood. More recent work has begun to translate these findings to clinically useful endpoints, by defining the relationship between DNA methylation alterations and cancer risk. This chapter highlights the existing research linking the environment, blood-derived DNA methylation alterations, and cancer risk, and points out how these epigenetic alterations may be contributing fundamentally to carcinogenesis.

  9. Pleomorphic Structures in Human Blood Are Red Blood Cell-Derived Microparticles, Not Bacteria

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    Mitchell, Adam J.; Gray, Warren D.; Schroeder, Max; Yi, Hong; Taylor, Jeannette V.; Dillard, Rebecca S.; Ke, Zunlong; Wright, Elizabeth R.; Stephens, David; Roback, John D.; Searles, Charles D.

    2016-01-01

    Background Red blood cell (RBC) transfusions are a common, life-saving therapy for many patients, but they have also been associated with poor clinical outcomes. We identified unusual, pleomorphic structures in human RBC transfusion units by negative-stain electron microscopy that appeared identical to those previously reported to be bacteria in healthy human blood samples. The presence of viable, replicating bacteria in stored blood could explain poor outcomes in transfusion recipients and have major implications for transfusion medicine. Here, we investigated the possibility that these structures were bacteria. Results Flow cytometry, miRNA analysis, protein analysis, and additional electron microscopy studies strongly indicated that the pleomorphic structures in the supernatant of stored RBCs were RBC-derived microparticles (RMPs). Bacterial 16S rDNA PCR amplified from these samples were sequenced and was found to be highly similar to species that are known to commonly contaminate laboratory reagents. Conclusions These studies suggest that pleomorphic structures identified in human blood are RMPs and not bacteria, and they provide an example in which laboratory contaminants may can mislead investigators. PMID:27760197

  10. Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

    NARCIS (Netherlands)

    Masoudi, E.A.; Ribas, J.; Kaushik, G.; Leijten, J.C.H.; Khademhosseini, A.

    2016-01-01

    Platelet-rich blood derivatives have been widely used in different fields of medicine and stem cell-based tissue engineering. They represent natural cocktails of autologous growth factors, which could provide an alternative for recombinant protein-based approaches. Platelet-rich blood derivatives, s

  11. Induction and identification of rabbit peripheral blood derived dendritic cells

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    Zhou, Jing; Yang, FuYuan; Chen, WenLi

    2012-03-01

    Purpose: To study a method of the induction of dendritic cells (DCs) from rabbit peripheral blood. Methods: Peripheral blood cells were removed from rabbit, filtered through nylon mesh. Peripheral blood mononuclear cells (PBMC) were isolated from the blood cells by Ficoll-Hypaque centrifugation (density of 1.077g/cm3).To obtain DCs, PBMC were cultured in RPMI1640 medium containing 10% fetal calf serum, 50U/mL penicillin and streptomycin, referred to subsequently as complete medium, at 37°C in 5% CO2 atmosphere for 4 hours. Nonadherent cells were aspirated, adherent cells were continued incubated in complete medium, supplemented with granulocyte/macrophage colony-stimulating factor (GM-CSF, 50ng/ml),and interleukin 4 (IL-4, 50ng/ml) for 9 days. Fluorescein labeled antibodies(anti-CD14, anti-HLA-DR, anti-CD86) were used to sign cells cultured for 3,6,9 days respectively, Then flow cytometry was performed. Results: Ratio of anti-HLA-DR and anti-CD86 labeled cells increased with induction time extension, in contrast with anti-CD14. Conclusion: Dendritic cells can be effectively induced by the method of this experiment, cell maturation status increased with induction time extension.

  12. Novel, high-yield red blood cell production methods from CD34-positive cells derived from human embryonic stem, yolk sac, fetal liver, cord blood, and peripheral blood.

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    Olivier, Emmanuel; Qiu, Caihong; Bouhassira, Eric E

    2012-08-01

    The current supply of red blood cells expressing rare blood groups is not sufficient to cover all the existing transfusion needs for chronically transfused patients, such as sickle cell disease homozygous carriers, because of alloimmunization. In vitro production of cultured red blood cells is slowly emerging as a possible complement to the existing collection-based red blood cell procurement system. The yield of cultured red blood cells can theoretically be maximized by amplifying the stem, progenitor, or precursor compartment. Here, we combined methods designed to expand these three compartments to optimize the yield of cultured red blood cells and found that exposing CD34(+) cells to a short pulse of cytokines favorable for erythroid differentiation prior to stem cell expansion followed by progenitor expansion produced the highest yield of erythroid cells. This novel serum-free red blood cell production protocol was efficient on CD34(+) cells derived from human embryonic stem cells, 6-8-week yolk sacs, 16-18-week fetal livers, cord blood, and peripheral blood. The yields of cells obtained with these new protocols were larger by an order of magnitude than the yields observed previously. Globin expression analysis by high-performance liquid chromatography revealed that these expansion protocols generally yielded red blood cells that expressed a globin profile similar to that expected for the developmental age of the CD34(+) cells.

  13. Study on the induction and differentiation of megakaryocyte progenitor cell derived from umbilical cord blood

    Institute of Scientific and Technical Information of China (English)

    陈琳

    2014-01-01

    Objective To build a protocol of separation and induction of megakaryocytes derived from cord blood mononuclear cells.Methods Red blood cells were precipitated by hydroxyethyl starch(HES).Mononuclear cells were obtained by density gradient centrifugation with Ficoll.The inducing efficiencies of megakaryocytes using different cytokine cocktails and culture media were analyzed.Results The best choice for erythrocyte sedimenta-

  14. GCD quantitation of opiates as propionyl derivatives in blood.

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    Mykkänen, S; Seppälä, J; Ariniemi, K; Lillsunde, P

    2000-03-01

    We describe a method using a gas chromatograph with electron ionization detection (GCD) for the simultaneous determination of morphine, codeine, 6-monoacetylmorphine, ethylmorphine, and dihydrocodeine in blood. The method employs propionic anhydride in the presence of triethylamine to propionylate free hydroxyl groups of the opiates in blood. The quantitation is achieved by using GCD with selected ion monitoring of the two most characteristic ions for each analyte. The quantitation limit was 0.01 mg/L and the linearity was 0.01-10 mg/L for dihydrocodeine, ethylmorphine, and 6-monoacetylmorphine. For the other investigated opiates, the quantitation limit was 0.025 mg/L and linearity was 0.025-10 mg/L. The intraday relative standard deviation (RSD) varied from 7.2 to 10% at the 0.5 mg/L level, and the day-to-day RSDs varied from 7.5 to 11% at the 0.85 mg/L level.

  15. Detection of Riddelliine-Derived DNA Adducts in Blood of Rats Fed Riddelliine

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    Ming W. Chou

    2002-09-01

    Full Text Available Abstract: We have previously shown that riddelliine, a naturally occurring genotoxic pyrrolizidine alkaloid, induces liver tumors in rats and mice through a genotoxic mechanism mediated by the formation of a set of eight 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine ( DHP-derived DNA adducts. In this study we report the formation of these DHP-derived DNA adducts in blood DNA of rats fed riddelliine. In an adduct formation and removal experiment, male and female F344 rats (8 weeks of age were administered riddelliine by gavage at a single dose of 10.0 mg/kg body weight in 0.1 M phosphate buffer. At 8, 24, 48, and 168 hrs after dosing, the levels of DHP-derived DNA adduct in blood and liver were determined by 32P-postlabeling/HPLC. Maximum DNA adduct formation occurred at 48 hr after treatment. From 48 to 168 hours, the adduct levels in female rat blood were 4-fold greater than those in male rats. In a dose response experiment, female rats were gavaged 0.1 and 1.0 mg/kg doses of riddelliine for three consecutive days and the DHPderived DNA adducts in blood DNA were assayed. The levels of the DHP-derived DNA adducts in blood of rats receiving 0.1 and 1.0 mg/kg doses were 12.9 and 51.8 adducts/107 nucleotides. These results suggest that: (i leucocyte DNA can bind with DHP to form a set of DHP-derived DNA adducts generated in liver; (ii DHP-derived DNA adducts in blood can serve as a potential non-invasive biomarkers for assessing the exposure to riddelliine.

  16. A novel mechanism of bacterial toxin transfer within host blood cell-derived microvesicles.

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    Anne-lie Ståhl

    2015-02-01

    Full Text Available Shiga toxin (Stx is the main virulence factor of enterohemorrhagic Escherichia coli, which are non-invasive strains that can lead to hemolytic uremic syndrome (HUS, associated with renal failure and death. Although bacteremia does not occur, bacterial virulence factors gain access to the circulation and are thereafter presumed to cause target organ damage. Stx was previously shown to circulate bound to blood cells but the mechanism by which it would potentially transfer to target organ cells has not been elucidated. Here we show that blood cell-derived microvesicles, shed during HUS, contain Stx and are found within patient renal cortical cells. The finding was reproduced in mice infected with Stx-producing Escherichia coli exhibiting Stx-containing blood cell-derived microvesicles in the circulation that reached the kidney where they were transferred into glomerular and peritubular capillary endothelial cells and further through their basement membranes followed by podocytes and tubular epithelial cells, respectively. In vitro studies demonstrated that blood cell-derived microvesicles containing Stx undergo endocytosis in glomerular endothelial cells leading to cell death secondary to inhibited protein synthesis. This study demonstrates a novel virulence mechanism whereby bacterial toxin is transferred within host blood cell-derived microvesicles in which it may evade the host immune system.

  17. Improved isolation protocol for equine cord blood-derived mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Thomsen, Preben Dybdahl; Betts, Dean H.

    2009-01-01

      BACKGROUND AIMS: A robust methodology for the isolation of cord blood-derived multipotent mesenchymal stromal cells (CB-MSCs) from fresh umbilical cord blood has not been reported in any species. The objective of this study was to improve the isolation procedure for equine CB-MSCs. METHODS: Pre-culture...... separation of red and white blood cells was done using either PrepaCyte?-EQ medium or Ficoll-Paque? PREMIUM density medium. Regular FBS and MSC-qualified FBS were compared for their ability to support the establishment of putative primary MSC colonies. RESULTS AND CONCLUSIONS: Our results indicate that Prepa...

  18. Comparison of corneal epitheliotrophic capacities among human platelet lysates and other blood derivatives

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    Huang, Chien-Jung; Sun, Yi-Chen; Christopher, Karen; Pai, Amy Shih-I; Lu, Chia-Ju; Hu, Fung-Rong; Lin, Szu-Yuan; Chen, Wei-Li

    2017-01-01

    Purpose To evaluate the corneal epitheliotropic abilities of two commercialized human platelet lysates (HPLs) and to compare the results with other blood derivatives, including human peripheral serum (HPS) and bovine fetal serum (FBS). Methods In vitro, human corneal epithelial cells were incubated in various concentrations (0%, 3%, 5% and 10%) of blood derivatives. Two commercialized HPLs, including UltraGRO TM (Helios, Atlanta, GA) and PLTMax (Mill Creek, Rochester, MI), were tested and compared with HPS and FBS. Scratch-induced directional wounding assay was performed to evaluate cellular migration. MTS assay was used to evaluate cellular proliferation. Cellular differentiation was examined by scanning electron microscopy, inverted microscopy and transepithelial electrical resistance. Sprague-Dawley rats were used to evaluate the effects of the blood derivatives on corneal epithelial wound healing in vivo. Different blood derivatives were applied topically every 2 hours for 2 days after corneal epithelial debridement. The concentrations of epidermal growth factor (EGF), transforming growth factor -β1 (TGF-β1), fibronectin, platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, and hyaluronic acid in different blood derivatives were evaluated by enzyme-linked immunosorbent assay (ELISA). Results In vitro experiments demonstrated statistically comparable epitheliotropic characteristics in cellular proliferation, migration, and differentiation for the two commercialized HPLs compared to FBS and HPS. Cells cultured without any serum were used as control group. The epitheliotropic capacities were statistically higher in the two commercialized HPLs compared to the control group (p<0.05). Among the different concentrations of blood derivatives, the preparations with 3% yielded better outcomes compared to 5% and 10%. In rats, HPLs also caused improved but not statistically significant wound healing compared to HPS. All the blood derivatives had better wound healing

  19. Phenotypic, functional, and quantitative characterization of canine peripheral blood monocyte-derived macrophages

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    R Bueno

    2005-08-01

    Full Text Available The yield as well as phenotypic and functional parameters of canine peripheral blood monocyte-derived macrophages were analyzed. The cells that remained adherent to Teflon after 10 days of culture had high phagocytic activity when inoculated with Leishmania chagasi. Flow cytometric analysis demonstrated that more than 80% of cultured cells were positive for the monocyte/macrophage marker CD14.

  20. In-vitro stem cell derived red blood cells for transfusion: are we there yet?

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    Kim, Hyun Ok

    2014-03-01

    To date, the use of red blood cells (RBCs) produced from stem cells in vitro has not proved practical for routine transfusion. However, the perpetual and widespread shortage of blood products, problems related to transfusion-transmitted infections, and new emerging pathogens elicit an increasing demand for artificial blood. Worldwide efforts to achieve the goal of RBC production through stem cell research have received vast attention; however, problems with large-scale production and cost effectiveness have yet to prove practical usefulness. Some progress has been made, though, as cord blood stem cells and embryonic stem cells have shown an ability to differentiate and proliferate, and induced pluripotent stem cells have been shown to be an unlimited source for RBC production. However, transfusion of stem cell-derived RBCs still presents a number of challenges to overcome. This paper will summarize an up to date account of research and advances in stem cell-derived RBCs, delineate our laboratory protocol in producing RBCs from cord blood, and introduce the technological developments and limitations to current RBC production practices.

  1. Antitumor activities of human dendritic cells derived from peripheral and cord blood

    Institute of Scientific and Technical Information of China (English)

    Jin-Kun Zhang; Jun Li; Hai-Bin Chen; Jin-Lun Sun; Yao-Juan Qu; Juan-Juan Lu

    2002-01-01

    AIM: To observe the biological specialization of humanperipheral blood dendritic cells (DC) and cord blood derivedDC and its effects on effector cells killing humanhepatocarcinoma cell line BEL-7402 in vitro.METHODS: The DC biological characteristics were detectedwith immunohistochemical and MTT assay. Two antitumorexperimental groups are: peripheral blood DC and cordblood DC groups. Peripheral blood DC groups used LAKcells as the effector cells and BEL-7402 as target cells, whilecord blood DC groups used CTL induced by tumor antigentwice pulsed DC as effector cells and BEL-7402 as targetcells, additional peripheral blood DC and cord blood DC areadded to observe its stimulating activities to effector cells.The effector's cytotoxicity to tumor cells were detected withneutral red colorimetric assay at two effector/target ratios of5:1 and 10: 1.RESULTS: Peripheral blood DC and cord blood DC highlyexpressed HLA-ABC, HLA-DR, HLA-DQ, CD54 and S-100protein. The stimulating activities to lymphocyteproliferation were compared between experimental groups(DC added) and control group (no DC added). In sixexperiment subgroups, the DC/lymphocyte ratio wassequentially 0.25: 100, 0.5: 100, 1: 100, 2: 100, 4: 100 and 8:100, A values(x± s) were 0.75396± 0.009, 0.84916± 0.010,0.90894± 0.012, 0.98371 ± 0.007, 1.01299 ± 0.006 and 1.20384± 0.006 in peripheral blood DC groups and 0.77650 ± 0.005,0.83008± 0.007, 0.92725 ± 0.007, 1.05990 ± 0.010, 1.15583 ±0.011, 1.22983 ± 0.011 in cord blood DC groups. A value was0.59517 ± 0.005 in control group. The stimulating activitieswere higher in experimental groups than in control group ( P< 0.01 ), which were increased when the DC concentrationwas enlarged ( P < 0.01 ). Two differently derived DCs hadthe same phenotypes and similar stimulating activities ( P >0.05). In peripheral blood DC groups, the cytotoxicity (x ±s) of the LD groups (experimental groups) and L groups(control group) was 58.16% ± 2.03% (5: 1), 46.18% ±2

  2. Monoclonal Antibodies as Probes for the Detection of Porcine Blood-Derived Food Ingredients.

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    Ofori, Jack A; Hsieh, Yun-Hwa P

    2016-05-11

    The lack of effective methods to monitor the use of porcine blood-derived food ingredients (PBFIs) is a concern for the billions of individuals who avoid consuming blood. We therefore sought to develop a panel of porcine blood-specific monoclonal antibodies (mAbs) for use as probes in immunoassays for the detection of PBFIs. Ten selected mAbs were identified that react with either a 60 or 90 kDa protein in the plasma fraction or a 12 kDa protein in the red blood cell fraction of porcine blood. Western blot analysis of commercially produced PBFIs revealed that these antigenic proteins are not affected by various manufacturing processes. The utility of these mAbs was demonstrated in a prototype sandwich ELISA developed for this study using mAbs 19C5-E10 and 16F9-C11. The new assay is porcine blood-specific and capable of detecting ≤0.03% (v/v) of PBFIs in cooked (100 °C for 15 min) ground meats or fish.

  3. Plasticity of human menstrual blood stem cells derived from the endometrium

    Institute of Scientific and Technical Information of China (English)

    Jian LIN; Dennis XIANG; Jin-long ZHANG; Julie ALLICKSON; Charlie XIANG

    2011-01-01

    Stem cells can be obtained from women's menstrual blood derived from the endometrium. The cells display stem cell markers such as Oct-4, SSEA-4, Nanog, and c-kit (CD117), and have the potent ability to differentiate into various cell types, including the heart, nerve, bone, cartilage, and fat. There has been no evidence of teratoma,ectopic formation, or any immune response after transplantation into an animal model. These cells quickly regenerate after menstruation and secrete many growth factors to display recurrent angiogenesis. The plasticity and safety of the acquired cells have been demonstrated in many studies. Menstrual blood-derived stem cells (MenSCs) provide an alternative source of adult stem cells for research and application in regenerative medicine. Here we summarize the multipotent properties and the plasticities of MenSCs and other endometrial stem cells from recent studies conducted both in vitro and in vivo.

  4. Genotyping Performance between Saliva and Blood-Derived Genomic DNAs on the DMET Array: A Comparison

    OpenAIRE

    Yueshan Hu; Erik A. Ehli; Kelly Nelson; Krista Bohlen; Christophina Lynch; Patty Huizenga; Julie Kittlelsrud; Soundy, Timothy J.; Davies, Gareth E.

    2012-01-01

    The Affymetrix Drug Metabolism Enzymes and Transporters (DMET) microarray is the first assay to offer a large representation of SNPs conferring genetic diversity across known pharmacokinetic markers. As a convenient and painless alternative to blood, saliva samples have been reported to work well for genotyping on the high density SNP arrays, but no reports to date have examined this application for saliva-derived DNA on the DMET platform. Genomic DNA extractions from saliva samples produced ...

  5. Blood flow in transplantable bladder tumors treated with hematoporphyrin derivative and light

    Energy Technology Data Exchange (ETDEWEB)

    Selman, S.H.; Kreimer-Birnbaum, M.; Klaunig, J.E.; Goldblatt, P.J.; Keck, R.W.; Britton, S.L.

    1984-05-01

    Following hematoporphyrin derivative (HPD) photochemotherapy, blood flow to transplantable N-(4-(5-nitro-2-furyl)-2-thia-zolyl) formamide-induced urothelial tumors was determined by a radioactive microsphere technique using either /sup 103/Ru or /sup 141/Ce. Two tumors were implanted s.c. on the abdominal wall of Fischer 344 weanling rats. HPD (10 mg/kg body weight) was administered 24 hr prior to phototherapy (red light, greater than 590 nm; 360 J/sq cm). One of the two tumors was shielded from light exposure and served as an internal control. Blood flows were determined in control animals that received no treatment (Group 1), HPD only (Group 2), or light only (Group 3). In Groups 4 and 5, animals received the combination of HPD and light but differed in the time interval between treatment and blood flow determinations (10 min and 24 hr, respectively). Only blood flow to tumors treated with HPD and light showed a significant decrease (p less than 0.05) when compared with their internal controls both at 10 min (Group 4) and 24 hr (Group 5) after completion of phototherapy. These studies suggest that disruption of tumor blood flow may be an important mechanism of action of this method of cancer therapy.

  6. Differentiation of Human Cord Blood and Stromal Derived Stem Cells into Neuron Cells

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    Özlem Pamukçu Baran

    2007-01-01

    Full Text Available The most basic properties of stem cells are the capacities to self-renew indefinitely and to differentiate into multiple cell or tissue types. Umbilical cord blood has been utilized for human hematopoietic stem cell transplantation as an alternative source to bone marrow.The experiments show that Wharton’s jelly cells are easily attainable and can be expanded in vitro, maintained in culture, and induced to differentiate into neural cells. Almost recent studies it has been discovered that the cord blood-derived cells can differantiate not only to blood cells but also to various somatic cells like neuron or muscle cell with the signals taken from the envoirenment.Interestingly, neural cells obtained from umbilical cord blood show a relatively high spontaneous differentiation into oligodendrocytes, Embryonic stem cells proliferate indefinitely and can differentiate spontaneously into all tissue types.It has been shown that embryonic stem cells can be induced to differentiate into neurons and glia by treatment with retinoic acid or basic fibroblast growth factor. It has been studied that the diseases as Motor Neuron Disease, Parkinson, Alzheimer and degeneration of medulla spinalis and also paralysises could be treated with transplantation of cord blood-dericed stem cells.

  7. Derivation of autism spectrum disorder-specific induced pluripotent stem cells from peripheral blood mononuclear cells.

    Science.gov (United States)

    DeRosa, Brooke A; Van Baaren, Jessica M; Dubey, Gaurav K; Lee, Joycelyn M; Cuccaro, Michael L; Vance, Jeffery M; Pericak-Vance, Margaret A; Dykxhoorn, Derek M

    2012-05-10

    Induced pluripotent stem cells (iPSCs) hold tremendous potential both as a biological tool to uncover the pathophysiology of disease by creating relevant cell models and as a source of stem cells for cell-based therapeutic applications. Typically, iPSCs have been derived by the transgenic overexpression of transcription factors associated with progenitor cell or stem cell function in fibroblasts derived from skin biopsies. However, the need for skin punch biopsies to derive fibroblasts for reprogramming can present a barrier to study participation among certain populations of individuals, including children with autism spectrum disorders (ASDs). In addition, the acquisition of skin punch biopsies in non-clinic settings presents a challenge. One potential mechanism to avoid these limitations would be the use of peripheral blood mononuclear cells (PBMCs) as the source of the cells for reprogramming. In this article we describe, for the first time, the derivation of iPSC lines from PBMCs isolated from the whole blood of autistic children, and their subsequent differentiation in GABAergic neurons.

  8. Blood compatibility of polyethersulfone membrane by blending a sulfated derivative of chitosan.

    Science.gov (United States)

    Xue, Jimin; Zhao, Weifeng; Nie, Shengqiang; Sun, Shudong; Zhao, Changsheng

    2013-06-01

    In this study, a novel sulfated derivative of chitosan, which could be dissolved in many common organic solvents, is conveniently synthesized for the modification of polyethersulfone (PES) membrane. Elemental analysis, FTIR, (1)H NMR and X-ray diffraction diagrams (XRD) are used to demonstrate the introduction of functional groups. Owing to the solubility in organic solvents, the sulfated derivative of chitosan could be directly blended with PES in organic solvent to prepare membrane by means of a liquid-liquid phase separation technique. The modified membrane showed lower protein (bovine serum albumin (BSA) and bovine serum fibrinogen (BFG)) adsorption and suppressed platelet adhesion. Moreover, the activated partial thromboplastin time (APTT) for the modified membrane was enhanced as high as 60% compared to pure PES membrane. The lower protein adsorption, suppressed platelet adhesion and increased APTT confirmed that the blood compatibility of the modified PES membrane by the sulfated derivative of chitosan was significantly improved.

  9. Isolation of mesenchymal stem cells from equine umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Thomsen Preben D

    2007-05-01

    Full Text Available Abstract Background There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC have been isolated from fresh umbilical cord blood of humans collected non-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low. The hypothesis of this study was that equine MSCs could be isolated from fresh whole equine cord blood. Results Cord blood was collected from 7 foals immediately after foaling. The mononuclear cell fraction was isolated by Ficoll density centrifugation and cultured in a DMEM low glucose based media at 38.5°C in humidified atmosphere containing 5% CO2. In 4 out of 7 samples colonies with MSC morphology were observed. Cellular morphology varied between monolayers of elongated spindle-shaped cells to layered cell clusters of cuboidal cells with shorter cytoplasmic extensions. Positive Alizarin Red and von Kossa staining as well as significant calcium deposition and alkaline phosphatase activity confirmed osteogenesis. Histology and positive Safranin O staining of matrix glycosaminoglycans illustrated chondrogenesis. Oil Red O staining of lipid droplets confirmed adipogenesis. Conclusion We here report, for the first time, the isolation of mesenchymal-like stem cells from fresh equine cord blood and their differentiation into osteocytes, chondrocytes and adipocytes. This novel isolation of equine cord blood MSCs and their preliminary in vitro differentiation positions the horse as the ideal pre-clinical animal model for proof-of-principle studies of cord blood derived MSCs.

  10. Evaluation of the expansion of umbilical cord blood derived from CD133+ cells on biocompatible microwells

    Directory of Open Access Journals (Sweden)

    Mina Soufizomorrod

    2016-05-01

    Full Text Available Background: Hematopoietic stem cell transplantation (HSCT is a therapeutic approach for treatment of hematological malignancies and incompatibility of Bone marrow. Umbilical cord blood (UCB has known as an alternative for hematopoietic stem/progenitor cells (HPSC in allogeneic transplantation. The low volume of collected samples is the main hindrance in application of HPSC derived from umbilical cord blood. So, ex vivo expansion of HPSCs is the useful approach to overcome this restriction. The goal of using this system is to produce appropriate amount of hematopoietic stem cells, which have the ability of transplantation and long term haematopoiesis. Material & Methods: In current study CD133+ cells were isolated from cord blood (CB. Isolated cells were seeded on microwells. Then expanded cells proliferation rate and ability in colony formation were assessed and finally were compared with 2 Dimensional (2D culture systems. Results: Our findings demonstrated that CD133+ cells derived from UCB which were cultivated on microwells had significantly higher rate of proliferation in compared with routine cell culture systems. Conclusion: In Current study, it was shown that CD133+ cells’ proliferations which were seeded on PDMS microwells coated with collagen significantly increased. We hope that 3 dimensional (3D microenvironment which mimics the 3D structure of bone marrow can solve the problem of using UCB as an alternative source of bone marrow.

  11. Integrated MicroRNA–mRNA Profiling Identifies Oncostatin M as a Marker of Mesenchymal-Like ER-Negative/HER2-Negative Breast Cancer

    Science.gov (United States)

    Bottai, Giulia; Diao, Lixia; Baggerly, Keith A.; Paladini, Laura; Győrffy, Balázs; Raschioni, Carlotta; Pusztai, Lajos; Calin, George A.; Santarpia, Libero

    2017-01-01

    MicroRNAs (miRNAs) simultaneously modulate different oncogenic networks, establishing a dynamic system of gene expression and pathway regulation. In this study, we analyzed global miRNA and messenger RNA (mRNA) expression profiles of 17 cell lines representing different molecular breast cancer subtypes. Spearman’s rank correlation test was used to evaluate the correlation between miRNA and mRNA expression. Hierarchical clustering and pathway analysis were also performed. Publicly available gene expression profiles (n = 699) and tumor tissues (n = 80) were analyzed to assess the relevance of key miRNA-regulated pathways in human breast cancer. We identified 39 significantly deregulated miRNAs, and the integration between miRNA and mRNA data revealed the importance of immune-related pathways, particularly the Oncostatin M (OSM) signaling, associated with mesenchymal-like breast cancer cells. OSM levels correlated with genes involved in the inflammatory response, epithelial-to-mesenchymal transition (EMT), and epidermal growth factor (EGF) signaling in human estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Our results suggest that the deregulation of specific miRNAs may cooperatively impair immune and EMT pathways. The identification of the OSM inflammatory pathway as an important mediator of EMT in triple-negative breast cancer (TNBC) may provide a novel potential opportunity to improve therapeutic strategies. PMID:28106823

  12. Cytokines and Growth Factors Stimulate Hyaluronan Production: Role of Hyaluronan in Epithelial to Mesenchymal-Like Transition in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Geraldine Chow

    2010-01-01

    Full Text Available In this study, we investigated the role of hyaluronan (HA in non-small cell lung cancer (NSCLC since close association between HA level and malignancy has been reported. HA is an abundant extracellular matrix component and its synthesis is regulated by growth factors and cytokines that include epidermal growth factor (EGF and interleukin-1β (IL-1β. We showed that treatment with recombinant EGF and IL-1β, alone or in combination with TGF-β, was able to stimulate HA production in lung adenocarcinoma cell line A549. TGF-β/IL-1β treatment induced epithelial to mesenchymal-like phenotype transition (EMT, changing cell morphology and expression of vimentin and E-cadherin. We also overexpressed hyaluronan synthase-3 (HAS3 in epithelial lung adenocarcinoma cell line H358, resulting in induced HA expression, EMT phenotype, enhanced MMP9 and MMP2 activities and increased invasion. Furthermore, adding exogenous HA to A549 cells and inducing HA H358 cells resulted in increased resistance to epidermal growth factor receptor (EGFR inhibitor, Iressa. Together, these results suggest that elevated HA production is able to induce EMT and increase resistance to Iressa in NSCLC. Therefore, regulation of HA level in NSCLC may be a new target for therapeutic intervention.

  13. Characterization of distinct mesenchymal-like cell populations from human skeletal muscle in situ and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Lecourt, Severine, E-mail: severine.lecourt@sls.aphp.fr [UPMC/AIM UMR S 974, Groupe Hospitalier Pitie-Salpetriere, Paris (France); INSERM U974, Groupe Hospitalier Pitie-Salpetriere, Paris (France); CNRS UMR 7215, Groupe Hospitalier Pitie-Salpetriere, Paris (France); Laboratoire de Therapie Cellulaire, Hopital Saint Louis, Paris (France); Marolleau, Jean-Pierre, E-mail: Marolleau.Jean-Pierre@chu-amiens.fr [Laboratoire de Therapie Cellulaire, Hopital Saint Louis, Paris (France); CHU Amiens Hopital Sud, Service d' Hematologie Clinique, UPJV, Amiens (France); Fromigue, Olivia, E-mail: olivia.fromigue@larib.inserm.fr [INSERM U606, Universite Paris 07, Hopital Lariboisiere, Paris (France); Vauchez, Karine, E-mail: k.vauchez@institut-myologie.org [UPMC/AIM UMR S 974, Groupe Hospitalier Pitie-Salpetriere, Paris (France); INSERM U974, Groupe Hospitalier Pitie-Salpetriere, Paris (France); CNRS UMR 7215, Groupe Hospitalier Pitie-Salpetriere, Paris (France); Genzyme S.A.S., Saint-Germain en Laye (France); Andriamanalijaona, Rina, E-mail: rinandria@yahoo.fr [Laboratoire de Biochimie des Tissus Conjonctifs, Faculte de Medecine, Caen (France); Ternaux, Brigitte, E-mail: brigitte.ternaux@orange.fr [Laboratoire de Therapie Cellulaire, Hopital Saint Louis, Paris (France); Lacassagne, Marie-Noelle, E-mail: mnlacassagne@free.fr [Laboratoire de Therapie Cellulaire, Hopital Saint Louis, Paris (France); Robert, Isabelle, E-mail: isa-robert@hotmail.fr [Laboratoire de Therapie Cellulaire, Hopital Saint Louis, Paris (France); Boumediene, Karim, E-mail: karim.boumediene@unicaen.fr [Laboratoire de Biochimie des Tissus Conjonctifs, Faculte de Medecine, Caen (France); Chereau, Frederic, E-mail: fchereau@pervasistx.com [Myosix S.A., Saint-Germain en Laye (France); Marie, Pierre, E-mail: pierre.marie@larib.inserm.fr [INSERM U606, Universite Paris 07, Hopital Lariboisiere, Paris (France); and others

    2010-09-10

    Human skeletal muscle is an essential source of various cellular progenitors with potential therapeutic perspectives. We first used extracellular markers to identify in situ the main cell types located in a satellite position or in the endomysium of the skeletal muscle. Immunohistology revealed labeling of cells by markers of mesenchymal (CD13, CD29, CD44, CD47, CD49, CD62, CD73, CD90, CD105, CD146, and CD15 in this study), myogenic (CD56), angiogenic (CD31, CD34, CD106, CD146), hematopoietic (CD10, CD15, CD34) lineages. We then analysed cell phenotypes and fates in short- and long-term cultures of dissociated muscle biopsies in a proliferation medium favouring the expansion of myogenic cells. While CD56{sup +} cells grew rapidly, a population of CD15{sup +} cells emerged, partly from CD56{sup +} cells, and became individualized. Both populations expressed mesenchymal markers similar to that harboured by human bone marrow-derived mesenchymal stem cells. In differentiation media, both CD56{sup +} and CD15{sup +} cells shared osteogenic and chondrogenic abilities, while CD56{sup +} cells presented a myogenic capacity and CD15{sup +} cells presented an adipogenic capacity. An important proportion of cells expressed the CD34 antigen in situ and immediately after muscle dissociation. However, CD34 antigen did not persist in culture and this initial population gave rise to adipogenic cells. These results underline the diversity of human muscle cells, and the shared or restricted commitment abilities of the main lineages under defined conditions.

  14. Effect of thiol derivatives on mixed mucus and blood clots in vitro.

    Science.gov (United States)

    Risack, L E; Vandevelde, M E; Gobert, J G

    1978-01-01

    The disintegrating effect of three reducing thiol derivatives: [sodium mercaptoethane sulphonate (Mesna), N-acetyl-L-cysteine (NAC) and dithio-1,4-threitol (DTT)] was investigated in vitro upon blood clots formed in the absence or in the presence of tracheobronchial secretions and compared with the effect of iso-osmotic saline solution. The amounts of haemoglobin released from the clots after 30 min incubation and the initial rates of haemoglobin release were compared for the different products at different concentrations. All three reducing agents showed some ability to disintegrate mixed clots to an extent depending on their concentration. After 30 min incubation, statistical analysis showed a highly significant difference in favour of Mesna at the three concentrations used, i.e. 0.1, 1.0 and 10 mmol/1. The initial rate of haemoglobin release in presence of Mesna was at all concentrations significantly higher than that of NAC or DTT. The effects on normal blood clots were much less pronounced. The effectiveness of Mesna in splitting up mixed blood and mucus clots in the management of patients who had inhaled blood is discussed.

  15. Differences between the genomes of lymphoblastoid cell lines and blood-derived samples

    Directory of Open Access Journals (Sweden)

    Joesch-Cohen LM

    2017-02-01

    Full Text Available Lena M Joesch-Cohen, Gustavo Glusman Institute for Systems Biology, Seattle, WA, USA Abstract: Lymphoblastoid cell lines (LCLs represent a convenient research tool for expanding the amount of biologic material available from an individual. LCLs are commonly used as reference materials, most notably from the Genome in a Bottle Consortium. However, the question remains how faithfully LCL-derived genome assemblies represent the germline genome of the donor individual as compared to the genome assemblies derived from peripheral blood mononuclear cells. We present an in-depth comparison of a large collection of LCL- and peripheral blood mononuclear cell-derived genomes in terms of distributions of coverage and copy number alterations. We found significant differences in the depth of coverage and copy number calls, which may be driven by differential replication timing. Importantly, these copy number changes preferentially affect regions closer to genes and with higher GC content. This suggests that genomic studies based on LCLs may display locus-specific biases, and that conclusions based on analysis of depth of coverage and copy number variation may require further scrutiny. Keywords: genomics, whole-genome sequencing, viral transformation, copy number changes, bioinformatics

  16. Influence of storage conditions on the release of growth factors in platelet-rich blood derivatives

    Directory of Open Access Journals (Sweden)

    Düregger Katharina

    2016-09-01

    Full Text Available Thrombocytes can be concentrated in blood derivatives and used as autologous transplants e.g. for wound treatment due to the release of growth factors such as platelet derived growth factor (PDGF. Conditions for processing and storage of these platelet-rich blood derivatives influence the release of PDGF from the platelet-bound α-granules into the plasma. In this study Platelet rich plasma (PRP and Platelet concentrate (PC were produced with a fully automated centrifugation system. Storage of PRP and PC for 1 h up to 4 months at temperatures between −20°C and +37°C was applied with the aim of evaluating the influence on the amount of released PDGF. Storage at −20°C resulted in the highest release of PDGF in PRP and a time dependency was determined: prolonged storage up to 1 month in PRP and 10 days in PC increased the release of PDGF. Regardless of the storage conditions, the release of PDGF per platelet was higher in PC than in PRP.

  17. Differentiation of human menstrual blood-derived endometrial mesenchymal stem cells into oocyte-like cells.

    Science.gov (United States)

    Lai, Dongmei; Guo, Ying; Zhang, Qiuwan; Chen, Yifei; Xiang, Charlie

    2016-11-01

    Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood are a unique stem cell source. Evidence suggests that EnSCs exhibit a multi-lineage potential and have attracted extensive attention in regenerative medicine. However, the potential of EnSCs to differentiate into germline cells in vitro remains unclear. In this study, EnSCs were induced to differentiate into germ cells in a differentiation medium supplemented with 20% human follicular fluid. Our results demonstrated that EnSCs derived from human menstrual blood form oocyte-like cells and express germ cell markers. The induced cell aggregates contained not only oocyte-like structures but also cells expressing follicle stimulating hormone receptor and luteotropic hormone receptor, and produced estrogen and progesterone regulated by gonodatropin, suggesting that granulosa-like and theca-like cells were also induced. We further found that granulosa cells promote the development of oocyte-like cells and activate the induction of blastocyst-like structures derived from EnSCs. In conclusion, EnSCs may potentially represent an in vitro system for the investigation of human folliculogenesis.

  18. Endothelial progenitor cell differentiation using cryopreserved, umbilical cord blood-derived mononuclear cells

    Institute of Scientific and Technical Information of China (English)

    Jun-ho JANG; Hugh C KIM; Sun-kyung KIM; Jeong-eun CHOI; Young-jin KIM; Hyun-woo LEE; Seok-yun KANG; Joon-seong PARK; Jin-hyuk CHOI; Ho-yeong LIM

    2007-01-01

    Aim: To investigate the endothelial differentiation potentiality of umbilical cord blood (UCB), we induced the differentiation of endothelial progenitor cells (EPC)from cryopreserved UCB-derived mononuclear cells (MNC). Methods: MNC from cryopreserved UCB and peripheral blood (PB) were cultured in M199 medium with endothelial cell growth supplements for 14 d. EPC were characterized by RT-PCR,flow cytometry, and immunocytochemistry analysis. The proliferation of differen-tiated EPC was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTI') assay, and vascular endothelial growth factor (VEGF) concentra-tion was measured using an ELISA kit. Characteristics of UCB-derived EPC were compared with those of PB-derived EPC. Results: A number of round-shaped cells were loosely attached to the bottom after 24 h culture, and numerous spindle-shaped cells began to appear from the round-shaped ones on d 7. Those cells expressed endothelial markers such as, Fit-1/VEGFR-1, ecNOS, VE-cadherin, yon Willebrand factor, and secreted VEGF. The patterns of endothelial markers of EPC from PB and UCB did not show striking differences. The results of the prolifera-tion and secretion of VEGF were also similar. Conclusion: We successfully cul-tured UCB cells stored at -196 ℃ into cells with the quality of endothelial cells.Those EPC could be used for angiogenic therapeutics by activating adjacent endothelial cells and enhancing angiogenesis.

  19. Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells.

    Science.gov (United States)

    Lippmann, Ethan S; Azarin, Samira M; Kay, Jennifer E; Nessler, Randy A; Wilson, Hannah K; Al-Ahmad, Abraham; Palecek, Sean P; Shusta, Eric V

    2012-08-01

    The blood-brain barrier (BBB) is crucial to the health of the brain and is often compromised in neurological disease. Moreover, because of its barrier properties, this endothelial interface restricts uptake of neurotherapeutics. Thus, a renewable source of human BBB endothelium could spur brain research and pharmaceutical development. Here we show that endothelial cells derived from human pluripotent stem cells (hPSCs) acquire BBB properties when co-differentiated with neural cells that provide relevant cues, including those involved in Wnt/β-catenin signaling. The resulting endothelial cells have many BBB attributes, including well-organized tight junctions, appropriate expression of nutrient transporters and polarized efflux transporter activity. Notably, they respond to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance (1,450 ± 140 Ω cm2), and they possess molecular permeability that correlates well with in vivo rodent blood-brain transfer coefficients.

  20. Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation.

    Science.gov (United States)

    Koshiar, Ruzica Livaja; Somajo, Sofia; Norström, Eva; Dahlbäck, Björn

    2014-01-01

    Elevated levels of erythrocyte-derived microparticles are present in the circulation in medical conditions affecting the red blood cells. Erythrocyte-derived microparticles expose phosphatidylserine thus providing a suitable surface for procoagulant reactions leading to thrombin formation via the tenase and prothrombinase complexes. Patients with elevated levels of circulating erythrocyte-derived microparticles have increased thrombin generation in vivo. The aim of the present study was to investigate whether erythrocyte-derived microparticles are able to support the anticoagulant reactions of the protein C system. Erythrocyte-derived microparticles were isolated using ultracentrifugation after incubation of freshly prepared erythrocytes with the ionophore A23187 or from outdated erythrocyte concentrates, the different microparticles preparations yielding similar results. According to flow cytometry analysis, the microparticles exposed phoshatidylserine and bound lactadherin, annexin V, and protein S, which is a cofactor to activated protein C. The microparticles were able to assemble the tenase and prothrombinase complexes and to stimulate the formation of thrombin in plasma-based thrombin generation assay both in presence and absence of added tissue factor. The addition of activated protein C in the thrombin generation assay inhibited thrombin generation in a dose-dependent fashion. The anticoagulant effect of activated protein C in the thrombin generation assay was inhibited by a monoclonal antibody that prevents binding of protein S to microparticles and also attenuated by anti-TFPI antibodies. In the presence of erythrocyte-derived microparticles, activated protein C inhibited tenase and prothrombinase by degrading the cofactors FVIIIa and FVa, respectively. Protein S stimulated the Arg306-cleavage in FVa, whereas efficient inhibition of FVIIIa depended on the synergistic cofactor activity of protein S and FV. In summary, the erythrocyte-derived microparticle

  1. Mathematical model for blood flow autoregulation by endothelium-derived relaxing factor

    CERN Document Server

    Chernyavsky, I L; Chernyavsky, Igor L.; Kudryashov, Nikolai A.

    2006-01-01

    The fluid shear stress is an important regulator of the cardiovascular system via the endothelium-derived relaxing factor (EDRF) that is Nitric Oxide. This mechanism involves biochemical reactions in an arterial wall. The autoregulation process is managed by the vascular tonus and gives the negative feedback for the shear stress changing. A new mathematical model for the autoregulation of a blood flow through arteria under the constant transmural pressure is presented. Endothelium-derived relaxing factor Nitric Oxide, the multi-layer structure of an arterial wall, and kinetic-diffusion processes are taken into consideration. The limit case of the thin-wall artery is analytically studied. The stability condition for a stationary point of the linearized system is given. The exact stationary solutions of the origin system are found. The numerical simulation for the autoregulation system is presented. It is shown the arteria adaptation to an initial radial perturbation and the transition of the system to new equi...

  2. Elevated peripheral blood mononuclear cell-derived superoxide production in healthy young black men.

    Science.gov (United States)

    Deo, Shekhar H; Holwerda, Seth W; Keller, David M; Fadel, Paul J

    2015-03-01

    Several studies have demonstrated that blacks exhibit elevations in systemic oxidative stress. However, the source(s) and mechanism(s) contributing to the elevation in oxidative stress remain unclear. Given that peripheral blood mononuclear cells (PBMCs) can be a major source of NADPH oxidase-derived superoxide production, we tested the hypothesis that young black men demonstrate greater superoxide production and NADPH oxidase expression in PBMCs compared with whites. PBMCs were freshly isolated from whole blood in young normotensive black (n = 18) and white (n = 16) men. Intracellular superoxide production in PBMCs was measured using dihydroethidium fluorescence, protein expression of NADPH oxidase subunits, gp91(phox) (membranous) and p47(phox) (cytosolic) in PBMCs were assessed using Western blot analysis, and plasma protein carbonyls were measured as a marker of systemic oxidative stress. Black men showed elevated intracellular superoxide production (4.3 ± 0.5 vs. 2.0 ± 0.6 relative fluorescence units; black men vs. white men, P superoxide production or NADPH oxidase subunit protein expression. These findings indicate that black men exhibit greater resting PBMC-derived superoxide production and an upregulation of the NADPH oxidase pathway with a possible contribution to increases in systemic oxidative stress.

  3. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection.

    Science.gov (United States)

    Sódar, Barbara W; Kittel, Ágnes; Pálóczi, Krisztina; Vukman, Krisztina V; Osteikoetxea, Xabier; Szabó-Taylor, Katalin; Németh, Andrea; Sperlágh, Beáta; Baranyai, Tamás; Giricz, Zoltán; Wiener, Zoltán; Turiák, Lilla; Drahos, László; Pállinger, Éva; Vékey, Károly; Ferdinandy, Péter; Falus, András; Buzás, Edit Irén

    2016-04-18

    Circulating extracellular vesicles have emerged as potential new biomarkers in a wide variety of diseases. Despite the increasing interest, their isolation and purification from body fluids remains challenging. Here we studied human pre-prandial and 4 hours postprandial platelet-free blood plasma samples as well as human platelet concentrates. Using flow cytometry, we found that the majority of circulating particles within the size range of extracellular vesicles lacked common vesicular markers. We identified most of these particles as lipoproteins (predominantly low-density lipoprotein, LDL) which mimicked the characteristics of extracellular vesicles and also co-purified with them. Based on biophysical properties of LDL this finding was highly unexpected. Current state-of-the-art extracellular vesicle isolation and purification methods did not result in lipoprotein-free vesicle preparations from blood plasma or from platelet concentrates. Furthermore, transmission electron microscopy showed an association of LDL with isolated vesicles upon in vitro mixing. This is the first study to show co-purification and in vitro association of LDL with extracellular vesicles and its interference with vesicle analysis. Our data point to the importance of careful study design and data interpretation in studies using blood-derived extracellular vesicles with special focus on potentially co-purified LDL.

  4. MIR517C inhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation.

    Science.gov (United States)

    Lu, Yuntao; Xiao, Limin; Liu, Yawei; Wang, Hai; Li, Hong; Zhou, Qiang; Pan, Jun; Lei, Bingxi; Huang, Annie; Qi, Songtao

    2015-01-01

    The epithelial-to-mesenchymal (-like) transition (EMT), a crucial embryonic development program, has been linked to the regulation of glioblastoma (GBM) progression and invasion. Here, we investigated the role of MIR517C/miR-517c, which belongs to the C19MC microRNA cluster identified in our preliminary studies, in the pathogenesis of GBM. We found that MIR517C was associated with improved prognosis in patients with GBM. Furthermore, following treatment with the autophagy inducer temozolomide (TMZ) and low glucose (LG), MIR517C degraded KPNA2 (karyopherin alpha 2 [RAG cohort 1, importin alpha 1]) and subsequently disturbed the nuclear translocation of TP53 in the GBM cell line U87 in vitro. Interestingly, this microRNA could inhibit autophagy and reduce cell migration and infiltration in U87 cells harboring wild-type (WT) TP53, but not in U251 cells harboring mutant (MU) TP53. Moreover, the expression of epithelial markers (i.e., CDH13/T-cadherin and CLDN1 [claudin 1]) increased, while the expression of mesenchymal markers (i.e., CDH2/N-cadherin, SNAI1/Snail, and VIM [vimentin]) decreased, indicating that the EMT status was blocked by MIR517C in U87 cells. Compared with MIR517C overexpression, MIR517C knockdown promoted infiltration of U87 cells to the surrounding structures in nude mice in vivo. The above phenotypic changes were also observed in TP53(+/+) and TP53(-/-) HCT116 colon cancer cells. In summary, our study provided support for a link between autophagy and EMT status in WT TP53 GBM cells and provided evidence for the signaling pathway (MIR517C-KPNA2-cytoplasmic TP53) involved in attenuating autophagy and eliminating the increased migration and invasion during the EMT.

  5. Melanoma affects the composition of blood cell-derived extracellular vesicles

    Directory of Open Access Journals (Sweden)

    Nina Koliha

    2016-07-01

    Full Text Available Extracellular vesicles are specifically loaded with nucleic acids, lipids, and proteins from their parental cell. Therefore, the constitution of extracellular vesicles reflects the type and status of the originating cell and extracellular vesicles in melanoma patient’s plasma could be indicative for the tumor. Likewise, extracellular vesicles might influence tumor progression by regulating immune responses. We performed a broad protein characterization of extracellular vesicles from plasma of melanoma patients and healthy donors as well as from T cells, B cells, natural killer cells, monocytes, monocyte-derived dendritic cells and platelets using a multiplex bead-based platform. Using this method, we succeeded in analyzing 58 proteins that were differentially displayed on extracellular vesicles. Hierarchal clustering of protein intensity patterns grouped extracellular vesicles according to their originating cell type. The analysis of extracellular vesicles from stimulated B cells and monocyte-derived dendritic cells revealed the transfer of surface proteins to vesicles depending on the cell status. The protein profiles of plasma vesicles resembled the protein profiles of extracellular vesicles from platelets, antigen presenting cells and natural cells as shown by platelet markers, costimulatory proteins, and a natural killer cell subpopulation marker. In comparison to healthy plasma vesicles, melanoma plasma vesicles showed altered signals for platelet markers indicating a changed vesicle secretion or protein loading of extracellular vesicles by platelets and a lower CD8 signal that might be associated with a diminished activity of natural killer cells or T cells. As we hardly detected melanoma-derived vesicles in patient’s plasma, we concluded that blood cells induced the observed differences. In summary, our results question a direct effect of melanoma cells on the composition of extracellular vesicles in melanoma plasma, but rather argue

  6. Impact of C-rel inhibition of cord blood-derived B-, T-, and NK cells.

    Science.gov (United States)

    Fallahi, Shirin; Mohammadi, Seyede Momeneh; Tayefi Nasrabadi, Hamid; Alihemmati, Alireza; Samadi, Naser; Gholami, Sanaz; Shanehbandi, Dariush; Nozad Charoudeh, Hojjatollah

    2017-12-01

    The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells. This particular source was selected as cord blood is an important source of cells used for transplantation and immunotherapy, primarily in treating leukemias. As stem cell factor (SCF) and FLT3 are important agents for hematopoietic stem cell expansion, and cytokines like interleukin (IL)-2, -7, and -15 are essential for T- and B- (and also NK) cell development and proliferation, the current study evaluated c-Rel expression in cord blood mononuclear cells and CD34(+ )cells, as well as effects on B-, T-, and NK cells associated with alterations in c-Rel expression, using flow cytometry and PCR. The results showed c-Rel expression increased among cells cultured in the presence of SCF and FLT3 but was reduced when IL-2, IL-7, and IL-15 were used all together. Further, inhibition of c-Rel expression by siRNA reduced cord blood-derived B-, T-, and NK cell differentiation and expansion. These results indicated that with cells isolated from cord blood, c-Rel has an important role in B-, T-, and NK cell differentiation and, further, that agents (select cytokines/growth factors) that could impact on its expression might not only affect immune cell profiles in a host but could potentially also limit apoptotic activities in (non-)immune cells in that host. In the context of cancer (immuno)therapy, in particular, when cord blood is used an important source in stem cell transplantation in

  7. Human umbilical cord blood-derived mesenchymal stem cells promote regeneration of crush-injured rat sciatic nerves

    Institute of Scientific and Technical Information of China (English)

    Mi-Ae Sung; Jong-Ho Lee; Hun Jong Jung; Jung-Woo Lee; Jin-Yong Lee; Kang-Mi Pang; Sang Bae Yoo; Mohammad S. Alrashdan; Soung-Min Kim; Jeong Won Jahng

    2012-01-01

    Several studies have demonstrated that human umbilical cord blood-derived mesenchymal stem cells can promote neural regeneration following brain injury. However, the therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells in guiding peripheral nerve regeneration remain poorly understood. This study was designed to investigate the effects of human umbilical cord blood-derived mesenchymal stem cells on neural regeneration using a rat sciatic nerve crush injury model. Human umbilical cord blood-derived mesenchymal stem cells (1 × 106) or a PBS control were injected into the crush-injured segment of the sciatic nerve. Four weeks after cell injection, brain-derived neurotrophic factor and tyrosine kinase receptor B mRNA expression at the lesion site was increased in comparison to control. Furthermore, sciatic function index, Fluoro Gold-labeled neuron counts and axon density were also significantly increased when compared with control. Our results indicate that human umbilical cord blood-derived mesenchymal stem cells promote the functional recovery of crush-injured sciatic nerves.

  8. Impact of Umbilical Cord Blood-Derived Mesenchymal Stem Cells on Cardiovascular Research

    Directory of Open Access Journals (Sweden)

    Santiago Roura

    2015-01-01

    Full Text Available Over the years, cell therapy has become an exciting opportunity to treat human diseases. Early enthusiasm using adult stem cell sources has been tempered in light of preliminary benefits in patients. Considerable efforts have been dedicated, therefore, to explore alternative cells such as those extracted from umbilical cord blood (UCB. In line, UCB banking has become a popular possibility to preserve potentially life-saving cells that are usually discarded after birth, and the number of UCB banks has grown worldwide. Thus, a brief overview on the categories of UCB banks as well as the properties, challenges, and impact of UCB-derived mesenchymal stem cells (MSCs on the area of cardiovascular research is presented. Taken together, the experience recounted here shows that UCBMSCs are envisioned as attractive therapeutic candidates against human disorders arising and/or progressing with vascular deficit.

  9. Impact of Umbilical Cord Blood-Derived Mesenchymal Stem Cells on Cardiovascular Research

    Science.gov (United States)

    Roura, Santiago; Pujal, Josep Maria; Gálvez-Montón, Carolina; Bayes-Genis, Antoni

    2015-01-01

    Over the years, cell therapy has become an exciting opportunity to treat human diseases. Early enthusiasm using adult stem cell sources has been tempered in light of preliminary benefits in patients. Considerable efforts have been dedicated, therefore, to explore alternative cells such as those extracted from umbilical cord blood (UCB). In line, UCB banking has become a popular possibility to preserve potentially life-saving cells that are usually discarded after birth, and the number of UCB banks has grown worldwide. Thus, a brief overview on the categories of UCB banks as well as the properties, challenges, and impact of UCB-derived mesenchymal stem cells (MSCs) on the area of cardiovascular research is presented. Taken together, the experience recounted here shows that UCBMSCs are envisioned as attractive therapeutic candidates against human disorders arising and/or progressing with vascular deficit. PMID:25861654

  10. Genetically engineered blood pharming: generation of HLA-universal platelets derived from CD34+ progenitor cells.

    Science.gov (United States)

    Figueiredo, Constança; Blaszczyk, Rainer

    2014-01-01

    Blood pharming is a recently designed concept to enable in vitro production of blood cells that are safe, effective and readily available. This approach represents an alternative to blood donation and may contribute to overcome the shortage of blood products. However, the high variability of the human leukocyte antigen (HLA) loci remains a major hurdle to the application of off-the-shelf blood products. Refractoriness to platelet (PLT) transfusion caused by alloimmunization against HLA class I antigens constitutes a relevant clinical problem. Thus, it would be desirable to generate PLT units devoid of HLA antigens. To reduce the immunogenicity of cell-based therapeutics, we have permanently reduced HLA class I expression using an RNA interference strategy. Furthermore, we demonstrated that the generation of HLA class I-silenced (HLA-universal) PLTs from CD34+ progenitor cells using an shRNA targeting β2-microglobulin transcripts is feasible. CD34+ progenitor cells derived from G-CSF mobilised donors were transduced with a lentiviral vector encoding for the β2-microglobulin-specific shRNA and differentiated into PLTs using a liquid culture system. The functionality of HLA-silenced PLTs and their ability to escape HLA antibody-mediated cytotoxicity were evaluated in vitro and in vivo. Platelet activation in response to ADP and thrombin were assessed in vitro. The immune-evasion capability of HLA-universal megakaryocytes (MKs) and PLTs was tested in lymphocytotoxicity assays using anti-HLA antibodies. To assess the functionality of HLA-universal PLTs in vivo, HLA-silenced MKs were infused into NOD/SCID/IL-2Rγc(-/-) mice with or without anti-HLA antibodies. PLT generation was evaluated by flow cytometry using anti-CD42a and CD61 antibodies. HLA-universal PLTs demonstrated to be functionally similar to blood-derived PLTs. Lymphocytotoxicity assays showed that HLA-silencing efficiently protects MKs against HLA antibody-mediated complement-dependent cytotoxicity. 80

  11. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve:viscoelasticity characterization

    Institute of Scientific and Technical Information of China (English)

    Xue-man Lv; Yan Liu; Fei Wu; Yi Yuan; Min Luo

    2016-01-01

    The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

  12. Protective role of a novel human erythrocyte-derived depressing factor on blood vessels in rats

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The protective role of a human erythrocyte-derived depressing factor (EDDF) on blood vessels was evaluated. The experiments were carried out on 25male Wistar rats aged 6-8 weeks, which were divided into control (n = 8), calcium overload (n = 8) and NG-L-nitro-arginine hypertensive model groups (L-NNA,n = 9), respectively. The isolated vascular ring perfusion assay, two-photon laser scanning fluorescence microscopy (TPM) and transmitted electron microscope were used to examine the effect of EDDF on vascular function and ultrastructure. Results showed that the contractile response of calcium overload rats and L-NNA rats to phenylephrine (PE) was significantly enhanced compared with that of the control (P < 0.05), and EDDF (10-3 g @mL-1) remarkably decreased the vascular contractile response of control's and calcium overload rats (P < 0.05),while EDDF had no effect on that of L-NNA rats. EDDF also alleviated the ultrastructural lesion of aorta VSMC in calcium overload rats by easing the abnormal in the nucleus, mitochondrion and other organell. It is concluded that EDDF could efficiently protect blood vessels against injury by influencing Ca2+ transport and ameliorating the lesion of VSMC, and further supported the hypothesis that the NO-cGMP pathway might contribute to the vasodilation and partially antihypertensive mechanism of EDDF.``

  13. Nanopatterned acellular valve conduits drive the commitment of blood-derived multipotent cells

    Science.gov (United States)

    Di Liddo, Rosa; Aguiari, Paola; Barbon, Silvia; Bertalot, Thomas; Mandoli, Amit; Tasso, Alessia; Schrenk, Sandra; Iop, Laura; Gandaglia, Alessandro; Parnigotto, Pier Paolo; Conconi, Maria Teresa; Gerosa, Gino

    2016-01-01

    Considerable progress has been made in recent years toward elucidating the correlation among nanoscale topography, mechanical properties, and biological behavior of cardiac valve substitutes. Porcine TriCol scaffolds are promising valve tissue engineering matrices with demonstrated self-repopulation potentiality. In order to define an in vitro model for investigating the influence of extracellular matrix signaling on the growth pattern of colonizing blood-derived cells, we cultured circulating multipotent cells (CMC) on acellular aortic (AVL) and pulmonary (PVL) valve conduits prepared with TriCol method and under no-flow condition. Isolated by our group from Vietnamese pigs before heart valve prosthetic implantation, porcine CMC revealed high proliferative abilities, three-lineage differentiative potential, and distinct hematopoietic/endothelial and mesenchymal properties. Their interaction with valve extracellular matrix nanostructures boosted differential messenger RNA expression pattern and morphologic features on AVL compared to PVL, while promoting on both matrices the commitment to valvular and endothelial cell-like phenotypes. Based on their origin from peripheral blood, porcine CMC are hypothesized in vivo to exert a pivotal role to homeostatically replenish valve cells and contribute to hetero- or allograft colonization. Furthermore, due to their high responsivity to extracellular matrix nanostructure signaling, porcine CMC could be useful for a preliminary evaluation of heart valve prosthetic functionality. PMID:27789941

  14. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  15. A successful experience of the Iranian blood transfusion organization in improving accessibility and affordability of plasma derived medicine.

    Science.gov (United States)

    Chegini, Azita; Torab, Seyed Ardeshir; Pourfatollah, Ali Akbar

    2017-02-01

    Plasma is the liquid part of blood. It is estimated 21.6 million liters of plasma collect from Whole blood annually. From these plasma, 4.2 million liters transfuse, 8.1 million liters fractionate, 9.3 million liters waste. Nowadays, blood products and PDM (plasma derived medicine) consider as essential medicine in modern health care and transfusion medicine. Iranian blood transfusion organization as a non-profit organization was established in 1974 in order to centralize all blood transfusion activities from donor recruitment to distribution of blood components to hospitals. Iran is the only country in EMR region with the rate of 20-29.9 blood donations per 1000 population and reached 100% voluntary non-remunerated blood donation in 2007. RBCs and platelets demand are much more than FFPs so the IBTO was faced the surplus plasma that could cause surplus plasma wastage. Simultaneously, hospitals need more plasma derived medicine especially albumin, IVIG, factor VIII, factor IX. IBTO was faced the challenges such as Fractionators selection, Plasma volume shipment, Contract duration, Product profile, Multiple External audits, Cold chain maintenance, Transporting plasma across international borders, NAT test. To overcome plasma wastage and storage of PDM. IBTO involved toll manufacturing in 2005 and not only prevents plasma wastage but also save MOH (ministry of health) budget.

  16. Mid-trimester fetal blood-derived adherent cells share characteristics similar to mesenchymal stem cells but full-term umbilical cord blood does not

    Institute of Scientific and Technical Information of China (English)

    MinjunYu; ZhifengXiao; LiShen; LingsongLi

    2005-01-01

    Stem cell transplantation is a promising treatment for many conditions.Although stem cells can be isolated from many tissues, blood is the ideal source of these cells due to the ease of collection. Mesenchymal stem cells (MSCs) have been paid increased attention because of their powerful proliferation and pluripotent differentiating ability. But whether MSCs reside in blood (newborn umbilical cord blood and fetal or adult peripheral blood) is also debatable. The present study showed that MSC-like cells could be isolated and expanded from 16-26 weeks fetal blood but were not acquired efficiently from full-term infants' umbilical cord blood (UCB). Adherent cells separated from postnatal UCB were heterogeneous in cell morphology. Their proliferation capacity was limited and they were mainly CD45+, which indicated their haematopoietic derivation. On the contrary, MSC-like cells shared a similar phenotype to bone marrow MSCs. They were CD34- CD45- CD44+ CD71+ CD90+ CD105+. They could be induced to differentiate into osteogenic, adipogenic and neural lineage cells. Single cell clones also showed similar phenotype and differentiation ability. Our results suggest that early fetal blood is rich in MSCs but term UCB is not.

  17. Blood

    Science.gov (United States)

    ... Also, blood is either Rh-positive or Rh-negative. So if you have type A blood, it's either A positive or A negative. Which type you are is important if you need a blood transfusion. And your Rh factor could be important ...

  18. Derivation of induced pluripotent stem cells from human peripheral blood T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Matthew E Brown

    Full Text Available Induced pluripotent stem cells (iPSCs hold enormous potential for the development of personalized in vitro disease models, genomic health analyses, and autologous cell therapy. Here we describe the generation of T lymphocyte-derived iPSCs from small, clinically advantageous volumes of non-mobilized peripheral blood. These T-cell derived iPSCs ("TiPS" retain a normal karyotype and genetic identity to the donor. They share common characteristics with human embryonic stem cells (hESCs with respect to morphology, pluripotency-associated marker expression and capacity to generate neurons, cardiomyocytes, and hematopoietic progenitor cells. Additionally, they retain their characteristic T-cell receptor (TCR gene rearrangements, a property which could be exploited for iPSC clone tracking and T-cell development studies. Reprogramming T-cells procured in a minimally invasive manner can be used to characterize and expand donor specific iPSCs, and control their differentiation into specific lineages.

  19. Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation

    Institute of Scientific and Technical Information of China (English)

    Chang Dong LI; Wei Yuan ZHANG; He Lian LI; Xiao Xia JIANG; Yi ZHANG; Pei Hsien TANG; Ning MAO

    2005-01-01

    Human placenta-derived mononuclear cells (MNC) were isolated by a Percoll density gradient and cultured in mesenchymal stem cell (MSC) maintenance medium.The homogenous layer of adherent cells exhibited a typical fibroblastlike morphology,a large expansive potential,and cell cycle characteristics including a subset of quiescent cells.In vitro differentiation assays showed the tripotential differentiation capacity of these cells toward adipogenic,osteogenic and chondrogenic lineages.Flow cytometry analyses and immunocytochemistry stain showed that placental MSC was a homogeneous cell population devoid of hematopoietic cells,which uniformly expressed CD29,CD44,CD73,CD 105,CD166,laminin,fibronectin and vimentin while being negative for expression of CD31,CD34,CD45 and α-smooth muscle actin.Most importantly,immuno-phenotypic analyses demonstrated that these cells expressed class I major histocompatibility complex (MHC-Ⅰ),but they did not express MHC-Ⅱ molecules.Additionally these cells could suppress umbilical cord blood (UCB) lymphocytes proliferation induced by cellular or nonspecific mitogenic stimuli.This strongly implies that they may have potential application in allograft transplantation.Since placenta and UCB are homogeneous,the MSC derived from human placenta can be transplanted combined with hematopoietic stem cells (HSC) from UCB to reduce the potential graft-versus-host disease (GVHD) in recipients.

  20. Identification of myeloid derived suppressor cells in the peripheral blood of tumor bearing dogs

    Directory of Open Access Journals (Sweden)

    Sherger Matthew

    2012-10-01

    Full Text Available Abstract Background Myeloid derived suppressor cells (MDSCs are a recently described population of immune cells that significantly contribute to the immunosuppression seen in cancer patients. MDSCs are one of the most important factors that limit the efficacy of cancer immunotherapy (e.g. cancer vaccines and MDSC levels are increased in cancer in multiple species. Identifying and targeting MDSCs is actively being investigated in the field of human oncology and is increasingly being investigated in veterinary oncology. The treatment of canine cancer not only benefits dogs, but is being used for translational studies evaluating and modifcying candidate therapies for use in humans. Thus, it is necessary to understand the immune alterations seen in canine cancer patients which, to date, have been relatively limited. This study investigates the use of commercially available canine antibodies to detect an immunosuppressive (CD11blow/CADO48low cell population that is increased in the peripheral blood of tumor-bearing dogs. Results Commercially available canine antibodies CD11b and CADO48A were used to evaluate white blood cells from the peripheral blood cells of forty healthy control dogs and forty untreated, tumor-bearing dogs. Tumor-bearing dogs had a statistically significant increase in CD11blow/CADO48Alow cells (7.9% as compared to the control dogs (3.6%. Additionally, sorted CD11blow/CADO48Alow generated in vitro suppressed the proliferation of canine lymphocytes. Conclusions The purpose of this study was aimed at identifying potential canine specific markers for identifying MDSCs in the peripheral blood circulation of dogs. This study demonstrates an increase in a unique CD11blow/CADO48Alow cell population in tumor-bearing dogs. This immunophenotype is consistent with described phenotypes of MDSCs in other species (i.e. mice and utilizes commercially available canine-specific antibodies. Importantly, CD11blow/CADO48Alow from a tumor environment

  1. Brain-derived neurotrophic factor induces neuron-like cellular differentiation of mesenchymal stem cells derived from human umbilical cord blood cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Lei Chen; Guozhen Hui; Zhongguo Zhang; Bing Chen; Xiaozhi Liu; Zhenlin Liu; Hongliang Liu; Gang Li; Zhiguo Su; Junfei Wang

    2011-01-01

    Human umbilical cord blood was collected from full-term deliveries scheduled for cesarean section. Mononuclear cells were isolated, amplified and induced as mesenchymal stem cells. Isolated mesenchymal stem cells tested positive for the marker CD29, CD44 and CD105 and negative for typical hematopoietic and endothelial markers. Following treatment with neural induction medium containing brain-derived neurotrophic factor for 7 days, the adherent cells exhibited neuron-like cellular morphology. Immunohistochemical staining and reverse transcription-PCR revealed that the induced mesenchymal stem cells expressed the markers for neuron-specific enolase and neurofilament. The results demonstrated that human umbilical cord blood-derived mesenchymal stem cells can differentiate into neuron-like cells induced by brain-derived neurotrophic factor in vitro.

  2. Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

    Science.gov (United States)

    Shah, Sandeep N; Gelderman, Monique P; Lewis, Emily M A; Farrel, John; Wood, Francine; Strader, Michael Brad; Alayash, Abdu I; Vostal, Jaroslav G

    2016-01-01

    Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

  3. [Single-donor (apheresis) platelets and pooled whole-blood-derived platelets--significance and assessment of both blood products].

    Science.gov (United States)

    Hitzler, Walter E

    2014-01-01

    The transfusion efficacy of ATK, which contain fully functional platelets, is beyond all doubt. The equivalence of ATK and PTK has been subject of many studies. Some of those studies show the superiority of ATK's, while others do not, but there have been no studies that demonstrated a superiority of PTK's. The superiority of platelets stored in plasma and in third generation additive solution was demonstrated in clinical studies; therefore, it cannot be said that all the platelet concentrates on the German market are equivalent in efficacy. Of decisive importance, above all, is the risk of transfusion-transmitted infections with known pathogens, or those not yet discovered. This risk is different for ATK compared to PTK. Taking this difference in risk and the difference in donor exposure of transfused patients into account, it can definitely be said that ATK and PTK are not equivalent. In 2012, the Robert-Koch-Institute (RKI) published a mathematical risk model for different platelet concentrates and assessed the risk of transmitting known pathogens such as HIV, HCV, and HBV. The risk was higher for PTK compared to ATK. The relative risks for PTK derived from 4BCs were 2.2 (95%--CI: 2.1-2.4) for HIV, 2.7 (95%--CI: 2.5-3.0) for HCV, and 2.2 (95%--CI: 2.8-3.7) for HBV. At the present time, these are the relative risks of transfusion-transmitted infections with the traditional pathogens for PTK compared to ATK. In addition to the RKI assessed risks, there is the theoretical risk of a new, unknown agent, transmitted through blood exposure. The magnitude of this risk is hardly predictable for PTK. The experience gathered so far, especially in the last three decades, with the emergence of HIV, prions, and West Nil virus, shows that the biological nature of a next transfusion-transmissible infectious agent cannot be predictable. This agent, if we think at a conventional sexually transmissible agent with nucleic acid and long latent period, would spread first in areas with

  4. Comparative capability of menstrual blood versus bone marrow derived stem cells in neural differentiation.

    Science.gov (United States)

    Azedi, Fereshteh; Kazemnejad, Somaieh; Zarnani, Amir Hassan; Soleimani, Masoud; Shojaei, Amir; Arasteh, Shaghayegh

    2017-02-01

    In order to characterize the potency of menstrual blood stem cells (MenSCs) for future cell therapy of neurological disorders instead of bone marrow stem cells (BMSCs) as a well-known and conventional source of adult stem cells, we examined the in vitro differentiation potential of these stem cells into neural-like cells. The differentiation potential of MenSCs to neural cells in comparison with BMSCs was assessed under two step neural differentiation including conversion to neurosphere-like cells and final differentiation. The expression levels of Nestin, Microtubule-associated protein 2, gamma-aminobutyric acid type B receptor subunit 1 and 2, and Tubulin, beta 3 class III mRNA and/or protein were up-regulated during development of MenSCs into neurosphere-like cells (NSCs) and neural-like cells. The up-regulation level of these markers in differentiated neural-like cells from MenSCs was comparable with differentiated cells from BMSCs. Moreover, both differentiated MenSCs and BMSCs expressed high levels of potassium, calcium and sodium channel genes developing functional channels with electrophysiological recording. For the first time, we demonstrated that MenSCs are a unique cell population with differentiation ability into neural-like cells comparable to BMSCs. In addition, we have introduced an approach to generate NSCs from MenSCs and BMSCs and their further differentiation into neural-like cells in vitro. Our results hold a promise to future stem cell therapy of neurological disorders using NSCs derived from menstrual blood, an accessible source in every woman.

  5. Adult derived genetic blood pressure scores and blood pressure measured in different body postures in young children

    NARCIS (Netherlands)

    Jansen, Maria Ac; Dalmeijer, Geertje W.; Visseren, Frank Lj; van der Ent, Cornelis K; Leusink, Maarten; Onland-Moret, N Charlotte; Der Zee, Anke H Maitland Van; Grobbee, Diederick E; Uiterwaal, CSPM

    2017-01-01

    Aims Several genes are related to blood pressure (BP) levels in adults, but it is largely unknown whether these genes also determine BP early in life. Methods Systolic BP (SBP) and diastolic BP (DBP) were measured in 720 5-year-old children from the WHeezing-Illnesses-STudy-LEidsche-Rijn (WHISTLER)

  6. Myeloperoxidase-derived oxidants induce blood-brain barrier dysfunction in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Andreas Üllen

    Full Text Available Peripheral leukocytes can exacerbate brain damage by release of cytotoxic mediators that disrupt blood-brain barrier (BBB function. One of the oxidants released by activated leukocytes is hypochlorous acid (HOCl formed via the myeloperoxidase (MPO-H2O2-Cl(- system. In the present study we examined the role of leukocyte activation, leukocyte-derived MPO and MPO-generated oxidants on BBB function in vitro and in vivo. In a mouse model of lipopolysaccharide (LPS-induced systemic inflammation, neutrophils that had become adherent released MPO into the cerebrovasculature. In vivo, LPS-induced BBB dysfunction was significantly lower in MPO-deficient mice as compared to wild-type littermates. Both, fMLP-activated leukocytes and the MPO-H2O2-Cl(- system inflicted barrier dysfunction of primary brain microvascular endothelial cells (BMVEC that was partially rescued with the MPO inhibitor 4-aminobenzoic acid hydrazide. BMVEC treatment with the MPO-H2O2-Cl(- system or activated neutrophils resulted in the formation of plasmalogen-derived chlorinated fatty aldehydes. 2-chlorohexadecanal (2-ClHDA severely compromised BMVEC barrier function and induced morphological alterations in tight and adherens junctions. In situ perfusion of rat brain with 2-ClHDA increased BBB permeability in vivo. 2-ClHDA potently activated the MAPK cascade at physiological concentrations. An ERK1/2 and JNK antagonist (PD098059 and SP600125, respectively protected against 2-ClHDA-induced barrier dysfunction in vitro. The current data provide evidence that interference with the MPO pathway could protect against BBB dysfunction under (neuroinflammatory conditions.

  7. Circulating angiogenic cells can be derived from cryopreserved peripheral blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Tanja Sofrenovic

    Full Text Available BACKGROUND: Cell transplantation for regenerative medicine has become an appealing therapeutic method; however, stem and progenitor cells are not always freshly available. Cryopreservation offers a way to freeze cells as they are generated, for storage and transport until required for therapy. This study was performed to assess the feasibility of cryopreserving peripheral blood mononuclear cells (PBMCs for the subsequent in vitro generation of their derived therapeutic population, circulating angiogenic cells (CACs. METHODS: PBMCs were isolated from healthy human donors. Freshly isolated cells were either analyzed immediately or cryopreserved in media containing 6% plasma serum and 5% dimethyl sulfoxide. PBMCs were thawed after being frozen for 1 (early thaw or 28 (late thaw days and analyzed, or cultured for 4 days to generate CACs. Analysis of the cells consisted of flow cytometry for viability and phenotype, as well as functional assays for their adhesion and migration potential, cytokine secretion, and in vivo angiogenic potential. RESULTS: The viability of PBMCs and CACs as well as their adhesion and migration properties did not differ greatly after cryopreservation. Phenotypic changes did occur in PBMCs and to a lesser extent in CACs after freezing; however the potent CD34(+VEGFR2(+CD133(+ population remained unaffected. The derived CACs, while exhibiting changes in inflammatory cytokine secretion, showed no changes in the secretion of important regenerative and chemotactic cytokines, nor in their ability to restore perfusion in ischemic muscle. CONCLUSION: Overall, it appears that changes do occur in cryopreserved PBMCs and their generated CACs; however, the CD34(+VEGFR2(+CD133(+ progenitor population, the secretion of pro-vasculogenic factors, and the in vivo angiogenic potential of CACs remain unaffected by cryopreservation.

  8. Point-of-care seeding of nitinol stents with blood-derived endothelial cells.

    Science.gov (United States)

    Jantzen, Alexandra E; Noviani, Maria; Mills, James S; Baker, Katherine M; Lin, Fu-Hsiung; Truskey, George A; Achneck, Hardean E

    2016-11-01

    Nitinol-based vascular devices, for example, peripheral and intracranial stents, are limited by thrombosis and restenosis. To ameliorate these complications, we developed a technology to promote vessel healing by rapidly seeding (QuickSeeding) autologous blood-derived endothelial cells (ECs) onto modified self-expanding nitinol stent delivery systems immediately before implantation. Several thousand micropores were laser-drilled into a delivery system sheath surrounding a commercial nitinol stent to allow for exit of an infused cell suspension. As suspension medium flowed outward through the micropores, ECs flowed through the delivery system attaching to the stent surface. The QuickSeeded ECs adhered to and spread on the stent surface following 24-h in vitro culture under static or flow conditions. Further, QuickSeeded ECs on stents that were deployed into porcine carotid arteries spread to endothelialize stent struts within 48 h (n = 4). The QuickSeeded stent struts produced significantly more nitric oxide in ex vivo flow circuits after 24 h, as compared to static conditions (n = 5). In conclusion, ECs QuickSeeded onto commercial nitinol stents within minutes of implantation spread to form a functional layer in vitro and in vivo, providing proof of concept that the novel QuickSeeding method with modified delivery systems can be used to seed functional autologous endothelium at the point of care. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1658-1665, 2016.

  9. The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease.

    Science.gov (United States)

    Lee, Hyun Ju; Lee, Jong Kil; Lee, Hyun; Shin, Ji-woong; Carter, Janet E; Sakamoto, Toshiro; Jin, Hee Kyung; Bae, Jae-sung

    2010-08-30

    The neuropathological hallmarks of Alzheimer's disease (AD) include the presence of extracellular amyloid-beta peptide (Abeta) in the form of amyloid plaques in the brain parenchyma and neuronal loss. The mechanism associated with neuronal death by amyloid plaques is unclear but oxidative stress and glial activation has been implicated. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are being scrutinized as a potential therapeutic tool to prevent various neurodegenerative diseases including AD. However, the therapeutic impact of hUCB-MSCs in AD has not yet been reported. Here we undertook in vitro work to examine the potential impact of hUCB-MSCs treatment on neuronal loss using a paradigm of cultured hippocampal neurons treated with Abeta. We confirmed that hUCB-MSCs co-culture reduced the hippocampal apoptosis induced by Abeta treatment. Moreover, in an acute AD mouse model to directly test the efficacy of hUCB-MSCs treatment on AD-related cognitive and neuropathological outcomes, we demonstrated that markers of glial activation, oxidative stress and apoptosis levels were decreased in AD mouse brain. Interestingly, hUCB-MSCs treated AD mice demonstrated cognitive rescue with restoration of learning/memory function. These data suggest that hUCB-MSCs warrant further investigation as a potential therapeutic agent in AD.

  10. A cord blood monocyte–derived cell therapy product accelerates brain remyelination

    Science.gov (United States)

    Buntz, Susan; Scotland, Paula; Xu, Li; Noeldner, Pamela; Patel, Sachit; Wollish, Amy; Gunaratne, Aruni; Gentry, Tracy; Matsushima, Glenn K.; Kurtzberg, Joanne; Balber, Andrew E.

    2016-01-01

    Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14+ monocytes. We compared the ability of freshly isolated CB CD14+ monocytes and DUOC-01 cells to accelerate remyelination of the brains of NOD/SCID/IL2Rγnull mice following cuprizone feeding–mediated demyelination. The corpus callosum of mice intracranially injected with DUOC-01 showed enhanced myelination, a higher proportion of fully myelinated axons, decreased gliosis and cellular infiltration, and more proliferating oligodendrocyte lineage cells than those of mice receiving excipient. Uncultured CB CD14+ monocytes also accelerated remyelination, but to a significantly lesser extent than DUOC-01 cells. Microarray analysis, quantitative PCR studies, Western blotting, and flow cytometry demonstrated that expression of factors that promote remyelination including PDGF-AA, stem cell factor, IGF1, MMP9, MMP12, and triggering receptor expressed on myeloid cells 2 were upregulated in DUOC-01 compared to CB CD14+ monocytes. Collectively, our results show that DUOC-01 accelerates brain remyelination by multiple mechanisms and could be beneficial in treating demyelinating conditions. PMID:27699230

  11. A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis.

    Science.gov (United States)

    Olsen, John A; Kenna, Lauren A; Tipon, Regine C; Spelios, Michael G; Stecker, Mark M; Akirav, Eitan M

    2016-08-01

    Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Minimally invasive biomarkers of MS are required for disease diagnosis and treatment. Differentially methylated circulating-free DNA (cfDNA) is a useful biomarker for disease diagnosis and prognosis, and may offer to be a viable approach for understanding MS. Here, methylation-specific primers and quantitative real-time PCR were used to study methylation patterns of the myelin oligodendrocyte glycoprotein (MOG) gene, which is expressed primarily in myelin-producing oligodendrocytes (ODCs). MOG-DNA was demethylated in O4(+) ODCs in mice and in DNA from human oligodendrocyte precursor cells (OPCs) when compared with other cell types. In the cuprizone-fed mouse model of demyelination, ODC derived demethylated MOG cfDNA was increased in serum and was associated with tissue-wide demyelination, demonstrating the utility of demethylated MOG cfDNA as a biomarker of ODC death. Collected sera from patients with active (symptomatic) relapsing-remitting MS (RRMS) demonstrated a higher signature of demethylated MOG cfDNA when compared with patients with inactive disease and healthy controls. Taken together, these results offer a minimally invasive approach to measuring ODC death in the blood of MS patients that may be used to monitor disease progression.

  12. Human umbilical cord blood-derived mesenchymal stem cells promote vascular growth in vivo.

    Directory of Open Access Journals (Sweden)

    Santiago Roura

    Full Text Available Stem cell therapies are promising strategies to regenerate human injured tissues, including ischemic myocardium. Here, we examined the acquisition of properties associated with vascular growth by human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs, and whether they promoted vascular growth in vivo. UCBMSCs were induced in endothelial cell-specific growth medium (EGM-2 acquiring new cell markers, increased Ac-LDL uptake, and migratory capacity as assessed by qRT-PCR, Western blotting, indirect immunofluorescence, and invasion assays. Angiogenic and vasculogenic potentials could be anticipated by in vitro experiments showing self organization into Matrigel-mediated cell networks, and activation of circulating angiogenic-supportive myeloid cells. In mice, following subcutaneous co-injection with Matrigel, UCBMSCs modified to co-express bioluminescent (luciferases and fluorescent proteins were demonstrated to participate in the formation of new microvasculature connected with the host circulatory system. Response of UCBMSCs to ischemia was explored in a mouse model of acute myocardial infarction (MI. UCBMSCs transplanted using a fibrin patch survived 4 weeks post-implantation and organized into CD31(+network structures above the infarcted myocardium. MI-treated animals showed a reduced infarct scar and a larger vessel-occupied area in comparison with MI-control animals. Taken together, the presented results show that UCBMSCs can be induced in vitro to acquire angiogenic and vasculogenic properties and contribute to vascular growth in vivo.

  13. Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Contribute to Chondrogenesis in Coculture with Chondrocytes

    Directory of Open Access Journals (Sweden)

    Xingfu Li

    2016-01-01

    Full Text Available Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs have been shown as the most potential stem cell source for articular cartilage repair. In this study, we aimed to develop a method for long-term coculture of human articular chondrocytes (hACs and hUCB-MSCs at low density in vitro to determine if the low density of hACs could enhance the hUCB-MSC chondrogenic differentiation as well as to determine the optimal ratio of the two cell types. Also, we compared the difference between direct coculture and indirect coculture at low density. Monolayer cultures of hUCB-MSCs and hACs were investigated at different ratios, at direct cell-cell contact groups for 21 days. Compared to direct coculture, hUCB-MSCs and hACs indirect contact culture significantly increased type II collagen (COL2 and decreased type I collagen (COL1 protein expression levels. SRY-box 9 (SOX9 mRNA levels and protein expression were highest in indirect coculture. Overall, these results indicate that low density direct coculture induces fibrocartilage. However, indirect coculture in conditioned chondrocyte cell culture medium can increase expression of chondrogenic markers and induce hUCB-MSCs differentiation into mature chondrocytes. This work demonstrates that it is possible to promote chondrogenesis of hUCB-MSCs in combination with hACs, further supporting the concept of novel coculture strategies for tissue engineering.

  14. Phenotypic and functional characterization of cytokine-induced killer cells derived from preterm and term infant cord blood.

    Science.gov (United States)

    Zhang, Qian; Wang, Lili; Luo, Chenghan; Shi, Zanyang; Cheng, Xinru; Zhang, Zhen; Yang, Yi; Zhang, Yi

    2014-11-01

    Cord blood has gradually become an important source for hematopoietic stem cell transplantation (HSCT) in the human, particularly in pediatric patients. Adoptive cellular immunotherapy of patients with hematologic malignancies after umbilical cord blood transplant is crucial. Cytokine‑induced killer (CIK) cells derived from cord blood are a new type of antitumor immune effector cells in tumor prevention and treatment and have increasingly attracted the attention of researchers. On the other hand, it has been suggested that preterm infant cord blood retains an early differentiation phenotype suitable for immunotherapy. Therefore, we determined the phenotypic and functional characterization of CIK cells derived from preterm infant cord blood (PCB-CIK) compared with CIK cells from term infant cord blood (TCB-CIK). Twenty cord blood samples were collected and classified into two groups based on gestational age. Cord blood mononuclear cells (CBMCs) were isolated, cultured and induced to CIK cells in vitro. We used flow cytometry to detect cell surface markers, FlowJo software to analyze the proliferation profile and intracellular staining to test the secretion of cytokines. Finally, we evaluated the antitumor activity of CIK cells against K562 in vitro. Compared with TCB-CIK, PCB-CIK cells demonstrated faster proliferation and higher expression of activated cell surface markers. The secretion of IL-10 was lower in PCB-CIK cells while the expression of perforin and CD107a had no significant difference between the two cell groups. PCB-CIK cells exhibited a high proliferation rate while the cytotoxic activity had no difference between the PCB-CIK and TCB-CIK cells. Hence preterm infant cord blood may be a potential source for immunotherapy.

  15. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury:a biomechanical evaluation

    Institute of Scientific and Technical Information of China (English)

    Zhong-jun Zhang; Ya-jun Li; Xiao-guang Liu; Feng-xiao Huang; Tie-jun Liu; Dong-mei Jiang; Xue-man Lv; Min Luo

    2015-01-01

    Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood stem cells. After 30 days, the maximum load, max-imum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neu-rotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These ifndings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, im-prove biomechanical properties, and contribute to the recovery after injury.

  16. Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Verdegaal, Els M

    2014-01-01

    Adoptive cell therapy (ACT) based on autologous T cell derived either from tumor as tumor-infiltrating lymphocytes (TILs) or from peripheral blood is developing as a key area of future personalized cancer therapy. TIL-based ACT is defined as the infusion of T cells harvested from autologous fresh...... review....

  17. [Significance of considering hemoglobin derivatives and acid-base balance in the evaluation of the blood oxygen-transport system].

    Science.gov (United States)

    Matiushichev, V B; Shamratova, V G; Krapivko, Iu K

    2009-12-01

    Factor analysis was used to study the pattern of relationships of a number of hematological parameters in clinically healthy young subjects and in patients with moderate anemia. The level of total hemoglobin and the concentration of red blood cells were ascertained to control blood oxygen-transporting function in not full measure and these might be referred to as basic characteristics only conventionally. To clarify the picture, these criteria should be supplemented by the information on other parameters. It is concluded that the introduction of the ratio of a number of hemoglobin derivatives, blood oxygen regimen and acid-base balance can substantially increase the validity of clinical opinions as to this blood function.

  18. Human cord blood derived immature basophils show dual characteristics, expressing both basophil and eosinophil associated proteins.

    Directory of Open Access Journals (Sweden)

    Jeanette Grundström

    Full Text Available Basophils are blood cells of low abundance associated with allergy, inflammation and parasite infections. To study the transcriptome of mature circulating basophils cells were purified from buffy coats by density gradient centrifugations and two-step magnetic cell sorting. However, after extensive analysis the cells were found to be transcriptionally inactive and almost completely lack functional mRNA. In order to obtain transcriptionally active immature basophils for analysis of their transcriptome, umbilical cord blood cells were therefore cultured in the presence of interleukin (IL-3 for 9 days and basophils were enriched by removing non-basophils using magnetic cell sorting. The majority of purified cells demonstrated typical metachromatic staining with Alcian blue dye (95% and expression of surface markers FcεRI and CD203c, indicating a pure population of cells with basophil-like phenotype. mRNA was extracted from these cells and used to construct a cDNA library with approximately 600 000 independent clones. This library served as tool to determine the mRNA frequencies for a number of hematopoietic marker proteins. It was shown that these cells express basophil/mast cell-specific transcripts, i.e. β-tryptase, serglycin and FcεRI α-chain, to a relatively low degree. In contrast, the library contained a high number of several eosinophil-associated transcripts such as: major basic protein (MBP, charcot leyden crystal (CLC, eosinophil cationic protein (ECP, eosinophil derived neurotoxin (EDN and eosinophil peroxidase (EPO. Out of these transcripts, MBP and EPO were the most frequently observed, representing 8% and 3.2% of the total mRNA pool, respectively. Moreover, in a proteome analysis of cultured basophils we identified MBP and EPO as the two most prominent protein bands, suggesting a good correlation between protein and mRNA analyses of these cells. The mixed phenotype observed for these cells strengthens the conclusion that

  19. Human cord blood derived immature basophils show dual characteristics, expressing both basophil and eosinophil associated proteins.

    Science.gov (United States)

    Grundström, Jeanette; Reimer, Jenny M; Magnusson, Sofia E; Nilsson, Gunnar; Wernersson, Sara; Hellman, Lars

    2012-01-01

    Basophils are blood cells of low abundance associated with allergy, inflammation and parasite infections. To study the transcriptome of mature circulating basophils cells were purified from buffy coats by density gradient centrifugations and two-step magnetic cell sorting. However, after extensive analysis the cells were found to be transcriptionally inactive and almost completely lack functional mRNA. In order to obtain transcriptionally active immature basophils for analysis of their transcriptome, umbilical cord blood cells were therefore cultured in the presence of interleukin (IL)-3 for 9 days and basophils were enriched by removing non-basophils using magnetic cell sorting. The majority of purified cells demonstrated typical metachromatic staining with Alcian blue dye (95%) and expression of surface markers FcεRI and CD203c, indicating a pure population of cells with basophil-like phenotype. mRNA was extracted from these cells and used to construct a cDNA library with approximately 600 000 independent clones. This library served as tool to determine the mRNA frequencies for a number of hematopoietic marker proteins. It was shown that these cells express basophil/mast cell-specific transcripts, i.e. β-tryptase, serglycin and FcεRI α-chain, to a relatively low degree. In contrast, the library contained a high number of several eosinophil-associated transcripts such as: major basic protein (MBP), charcot leyden crystal (CLC), eosinophil cationic protein (ECP), eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EPO). Out of these transcripts, MBP and EPO were the most frequently observed, representing 8% and 3.2% of the total mRNA pool, respectively. Moreover, in a proteome analysis of cultured basophils we identified MBP and EPO as the two most prominent protein bands, suggesting a good correlation between protein and mRNA analyses of these cells. The mixed phenotype observed for these cells strengthens the conclusion that eosinophils and

  20. Factors inducing human umbilical cord blood-derived mesenchymal stem cells to differentiate into neuron-like cells

    Institute of Scientific and Technical Information of China (English)

    Nawei Zhang; Fengqing Ji

    2006-01-01

    OBJECTIVE:Human umbilical cord blood-derived mesenchymal stem cells (HUCB-derived MSCs)can differentiate into neuron-like cells,which can be used to treat some central nervous system(CNS)diseases.To investigate the factors,which can induce HUCB-derived MSCs to differentiate into neuron-like cells,so as to find effective methods for future clinical application.DATA SOURCES:Using the key terms"human umbilical cord blood"combined with"mesenchymal stem cells,neuron-like cells,neural cells"respectively,the relevant articles in English published during the period from January 1999 to June 2006 were searched from the Medline database.Meanwhile,relevant Chinese articles published from January 1999 to June 2006 were searched Using the same key terms.STUDY SELECTION: All articles associated with the differentiation from human umbilical cord blood into neuron-like cells were selected firstly.Then the full texts were looked up by searchling Ovid medical Journals full-text database and Elsevier Electrical Journals Full-text Database.Articles with full expeiments,enrolled in inducible factors or involved inducible mechanism were retdeved.DATA EXTRACTION:Among 119 collected correlative articles,29 were involved and 90 were excluded.DATA SYNTHESIS:The inducible factors of HUCB-derived MSCs differentiatling into neuron-like cells included renal endothelial growth factors,fibroblasts,β-mercaptoethanol,dimethyl sulfoxide,butyl hydroxyl anisol,brain-derived neurotrophic factor,Danshen,retinoic acid,sodium ferulate and so on,but its mechanism was unclear.CONCLUSION:Human umbilical cord blood-derived MSCs can differentiate into neuron-like cells,with varied inductors.

  1. Are Peripheral Blood Mononuclear Cells Derived from Patients with Certain Myopathies Suitable for Personalized Drug Screening?

    Directory of Open Access Journals (Sweden)

    Andriy V. Shatillo

    2014-12-01

    Full Text Available Background: Limb girdle muscular dystrophies (LGMDs and several other disorders which share their specific phenotype are rare, predominantly hereditary conditions with no curative treatment. Differential diagnosis of these myopathies is quite challenging and expensive in many cases. Therefore, a significant proportion of patients remains undiagnosed and untreated for a long time. At the same time there is a huge amount of drugs and supplements potentially able to modify the course of some of these muscular dystrophies. That is why a simple empirical approach able to define a patient’s reaction to a specific compound seems rational. Because most common basic pathogenetic mechanisms for these quite different disorders increase the vulnerability of muscle cells (or decrease ability for reparation during mechanical stress, we propose a simple, noninvasive and inexpensive approach for individualized drug screening based on the drug’s influence on the mechanical vulnerability of peripheral blood mononuclear cells (PBMC. Methods: PBMC derived from 8 patients with Duchenne muscular dystrophy (DMD, 2 patients with LGMD2A, 1 patient with LGMD2B, 1 with MERRF syndrome, 1 with facioscapulohumeral muscular dystrophy (FSHD and 13 matched control subjects were irradiated by ultrasound in the presence of several compounds (lisinopril, vitamin D3, prednisolon, tocopherol, topiramate, glutargin, α-lipoic acid, essentiale, and physiological solution. Then viability indexes of the samples were detected by citotoxic assays based on vital dye (neutral red and resazurin metabolism. Results: In cytotoxicity tests with active transport of neutral red into PBMC derived from DMD patients, the cells showed signs of destruction at 1.06±0.52 minutes of ultrasounding compared to 1.75±0.6 minutes in control. PBMCs from patients with other myopathies have either normal or decreased resistance to ultrasound. The addition of tocopherol significantly changes the PBMC

  2. DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients

    Science.gov (United States)

    Lázaro-Ibáñez, Elisa; Peris-Celda, María; Alonso, Marta M.; Guzmán-De-Villoria, Juan; Fernández-Carballal, Carlos; de Mendivil, Ana Ortiz; García-Duque, Sara; Escobedo-Lucea, Carmen; Prat-Acín, Ricardo; Belda-Iniesta, Cristóbal; Ayuso-Sacido, Angel

    2017-01-01

    Tumor-cell-secreted extracellular vesicles (EVs) can cross the disrupted blood-brain barrier (BBB) into the bloodstream. However, in certain gliomas, the BBB remains intact, which might limit EVs release. To evaluate the ability of tumor-derived EVs to cross the BBB, we used an orthotopic xenotransplant mouse model of human glioma-cancer stem cells featuring an intact BBB. We demonstrated that all types of tumor cells-derived EVs−apoptotic bodies, shedding microvesicles and exosomes−cross the intact BBB and can be detected in the peripheral blood, which provides a minimally invasive method for their detection compared to liquid biopsies obtained from cerebrospinal fluid (CSF). Furthermore, these EVs can be readily distinguished from total murine EVs, since they carry human-specific DNA sequences relevant for GBM biology. In a small cohort of glioma patients, we finally demonstrated that peripheral blood EVs cargo can be successfully used to detect the presence of IDH1G395A, an essential biomarker in the current management of human glioma PMID:27902458

  3. The in Vitro Assessment of Biochemical Factors in Hepatocyte like Cells Derived from Umbilical Cord Blood Stem Cells

    Directory of Open Access Journals (Sweden)

    A KHoramroodi

    2009-10-01

    Full Text Available Introduction & Objective: Umbilical cord blood (UCB is a source of Hematopoietic Stem Cells (HSC and progenitor cells that can reconstitute the hematopoietic system in patients with malignant and nonmalignant disorders. Mesenchymal stem cell-derived from umbilical cord blood (UCB have been differentiated to some kind of cells, such as osteobblast, adipoblast and chondroblast in Vitro. This study examined the differentiation of Umbilical Cord Blood (UCB derived stem cells to functional hepatocytes. Materials & Methods: The present study was an experimental study which was carried out in the Payam-e-Noor University of Tehran in cooperation with Hamedan University of Medical Sciences in 2008. Umbilical cord blood (UCB was obtained from Fatemieh hospital (Hamadan, Iran. Stem cells were isolated from the cord blood by combining density gradient centrifugation with plastic adherence. When the isolated cells reached 80% confluence, they differentiated to hepatocyte like cells. The medium which was used was consists of DMEM and 10% Fetal Bovine Serum (FBS supplemented with 20 ng/mL Hepatocyte Growth Factor (HGF, 10 ng/mL basic Fibroblast Growth Factor (bFGF and 20 ng/mL Oncostatin M (OSM.The medium was changed every 3 days and stored for Albumin (ALB, Alpha Fetoprotein (AFP, Alkaline Phosphatase (ALP, and urea assay. Finally PAS stain was done to study Glycogen storage in the differentiated cell. Results: Measurement of biochemical factors in different days showed that concentration of albumin (ALB, alpha fetoprotein (AFP, alkaline phosphatase (ALP, and Urea gradually increased. Also, PAS staining showed the storage of glycogen in these cells. Conclusion: Stem cell-derived from human umbilical cord blood (HUCB is a new source of cell types for cell transplantation therapy of hepatic diseases and under certain conditions these cells can differentiate into liver cells.

  4. [The strategy for preventing HIV/AIDS transmission via the blood and its derivatives in Mexico].

    Science.gov (United States)

    Sepúlveda-Amor, J; del Río-Zolezzi, A; Valdespino-Gómez, J L; García-García, M de L; Velázquez-Velázquez, L; Volkow, P

    1995-01-01

    This study presents blood-associated AIDS epidemic trends in Mexico, including cases due to blood transfusions, cases in professional blood donors and hemophiliacs. We present also an overview of preventive measures--both legal and educative--undertaken to prevent this type of transmission and its effects on the epidemic. The first blood-associated AIDS cases in Mexico were reported in 1985, since then and up to July 1, 1994 a total of 1,728 adult cases and 116 pediatric cases have been reported (12.3% and 25% of the total cases, respectively). As in many other parts in the world, in Mexico women were markedly affected by this form of transmission; the women to men morbidity ratio is 1.35. Another group particularly affected by AIDS in Mexico are professional blood donors, who were infected because of improper management and recycling of blood transfusion centers bank materials such as plasmapheresis sets, in some blood transfusion centers in our country. Blood screening is mandatory for all blood donors in Mexico since May, 1986. A year later blood commercialization was banned because of the extremely high HIV infection prevalences found in some professional blood donors (7.2%). Since that time a whole set of preventive measures has been implemented in our country, including blood quality and safety control as well as educative interventions. Results of these measures began to become evident by the end of 1991, when newly reported blood associated AIDS cases started to decrease, as opposed to their continuous growth seen in previous years. Up to July 1, 1994 we estimate that a total of 2,750 AIDS cases have been prevented through these measures, recovering an average of 36 years of potential life for each of them. Although blood transmission preventive measures have rendered significant achievements, we still have to face some very complex challenges such as potential ruralization of the epidemic and its impact on HIV infection prevalences among potential blood

  5. Novel UDP-GalNAc Derivative Structures Provide Insight into the Donor Specificity of Human Blood Group Glycosyltransferase.

    Science.gov (United States)

    Wagner, Gerd K; Pesnot, Thomas; Palcic, Monica M; Jørgensen, Rene

    2015-12-25

    Two closely related glycosyltransferases are responsible for the final step of the biosynthesis of ABO(H) human blood group A and B antigens. The two enzymes differ by only four amino acid residues, which determine whether the enzymes transfer GalNAc from UDP-GalNAc or Gal from UDP-Gal to the H-antigen acceptor. The enzymes belong to the class of GT-A folded enzymes, grouped as GT6 in the CAZy database, and are characterized by a single domain with a metal dependent retaining reaction mechanism. However, the exact role of the four amino acid residues in the specificity of the enzymes is still unresolved. In this study, we report the first structural information of a dual specificity cis-AB blood group glycosyltransferase in complex with a synthetic UDP-GalNAc derivative. Interestingly, the GalNAc moiety adopts an unusual yet catalytically productive conformation in the binding pocket, which is different from the "tucked under" conformation previously observed for the UDP-Gal donor. In addition, we show that this UDP-GalNAc derivative in complex with the H-antigen acceptor provokes the same unusual binding pocket closure as seen for the corresponding UDP-Gal derivative. Despite this, the two derivatives show vastly different kinetic properties. Our results provide a important structural insight into the donor substrate specificity and utilization in blood group biosynthesis, which can very likely be exploited for the development of new glycosyltransferase inhibitors and probes.

  6. A Simple Adaptive Transfer Function for Deriving the Central Blood Pressure Waveform from a Radial Blood Pressure Waveform.

    Science.gov (United States)

    Gao, Mingwu; Rose, William C; Fetics, Barry; Kass, David A; Chen, Chen-Huan; Mukkamala, Ramakrishna

    2016-09-14

    Generalized transfer functions (GTFs) are available to compute the more relevant central blood pressure (BP) waveform from a more easily measured radial BP waveform. However, GTFs are population averages and therefore may not adapt to variations in pulse pressure (PP) amplification (ratio of radial to central PP). A simple adaptive transfer function (ATF) was developed. First, the transfer function is defined in terms of the wave travel time and reflection coefficient parameters of an arterial model. Then, the parameters are estimated from the radial BP waveform by exploiting the observation that central BP waveforms exhibit exponential diastolic decays. The ATF was assessed using the original data that helped popularize the GTF. These data included radial BP waveforms and invasive reference central BP waveforms from cardiac catheterization patients. The data were divided into low, middle, and high PP amplification groups. The ATF estimated central BP with greater accuracy than GTFs in the low PP amplification group (e.g., central systolic BP and PP root-mean-square-errors of 3.3 and 4.2 mm Hg versus 6.2 and 7.1 mm Hg; p ≤ 0.05) while showing similar accuracy in the higher PP amplification groups. The ATF may permit more accurate, non-invasive central BP monitoring in elderly and hypertensive patients.

  7. A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells

    Directory of Open Access Journals (Sweden)

    Zhou YF

    2015-05-01

    Full Text Available Yanfang Zhou,1,* Jiemei Li,1,* Fang Lu,1 Junjie Deng,2 Jiahua Zhang,1 Peijie Fang,1 Xinsheng Peng,1 Shu-Feng Zhou3 1Guangdong Medical Universtity, Dongguan, Guangdong, People’s Republic of China; 2Department of Materials Science and Engineering, Drexel University, Philadelphia, PA, USA; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA *These authors contributed equally to this work Abstract: Dendrimers are hyperbranched macromolecules with well-defined topological structures and multivalent functionalization sites, but they may cause cytotoxicity due to the presence of cationic charge. Recently, we have introduced alkyne-terminated poly(amidoamine (PAMAM dendrons of different generations (G=2,3 into chitosan to obtain dendronized chitosan derivatives [Cs-g-PAMAM (G=2,3], which exhibited a better water solubility and enhanced plasmid DNA transfection efficiency. In this study, we attempted to examine the impact of Cs-g-PAMAM (G=2,3 at different concentrations (25 µg/mL, 50 µg/mL, and 100 µg/mL on the morphology, surface structure, and viability of rat red blood cells (RBCs. The results showed that treatment of RBCs with Cs-g-PAMAM (G=2,3 at 50 µg/mL and 100 µg/mL induced a slightly higher hemolysis than Cs, and Cs-g-PAMAM (G=3 caused a slightly higher hemolysis than Cs-g-PAMAM (G=2, but all values were <5.0%. Optical microscopic and atomic force microscopic examinations indicated that Cs-g-PAMAM (G=2,3 caused slight RBC aggregation and lysis. Treatment of RBCs with 100 µg/mL Cs-g-PAMAM (G=3 induced echinocytic transformation, and RBCs displayed characteristic irregular contour due to the folding of the periphery. Drephanocyte-like RBCs were observed when treated with 100 µg/mL Cs-g-PAMAM (G=3. Erythrocytes underwent similar shape transition upon treatment with Cs-g-PAMAM (G=2 or Cs. The roughness values (Rms of RBCs incubated with Cs-g-PAMAM (G=2,3 were significantly larger

  8. Effect of intracranial transplantation of CD34+ cells derived from human umbilical cord blood in rats with cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    LIU Hai-ying; ZHANG Qing-jun; LI Hong-jun; HAN Zhong-chao

    2006-01-01

    @@ As a source of transplantable stem cells, the CD34+ subpopulation in human umbilical cord blood (HUCB) has been used extensively to treat some hematopoietic system diseases. However,whether CD34+ cells hold the therapeutic potential to cerebral ischemia is unknown. The purpose of this study was to observe the recovery of neural function after transplantation of CD34+ cells derived from HUCB into ischemic cerebral tissue in rats.

  9. Good manufacturing practice-compliant isolation and culture of human umbilical cord blood-derived mesenchymal stem cells

    OpenAIRE

    Van Pham, Phuc; Vu, Ngoc Bich; Pham, Vuong Minh; Truong, Nhung Hai; Pham, Truc Le-Buu; Dang, Loan Thi-Tung; Nguyen, Tam Thanh; Bui, Anh Nguyen-Tu; Phan, Ngoc Kim

    2014-01-01

    Background Mesenchymal stem cells (MSCs) are an attractive source of stem cells for clinical applications. These cells exhibit a multilineage differentiation potential and strong capacity for immune modulation. Thus, MSCs are widely used in cell therapy, tissue engineering, and immunotherapy. Because of important advantages, umbilical cord blood-derived MSCs (UCB-MSCs) have attracted interest for some time. However, the applications of UCB-MSCs are limited by the small number of recoverable U...

  10. Functional and Pharmacological Analysis of Cardiomyocytes Differentiated from Human Peripheral Blood Mononuclear-Derived Pluripotent Stem Cells

    OpenAIRE

    2014-01-01

    Summary Advances in induced pluripotent stem cell (iPSC) technology have set the stage for routine derivation of patient- and disease-specific human iPSC-cardiomyocyte (CM) models for preclinical drug screening and personalized medicine approaches. Peripheral blood mononuclear cells (PBMCs) are an advantageous source of somatic cells because they are easily obtained and readily amenable to transduction. Here, we report that the electrophysiological properties and pharmacological responses of ...

  11. Expression and the role of myeloid-derived suppressor cells in the peripheral blood in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    陆丽蓉

    2014-01-01

    Objective To investigate the correlation between the frequency of myeloid-derived suppressor cells(MDSC)and the frequency of regulatory T cells(Treg)in the peripheral blood in patients with chronic hepatitis B(CHB)and its clinical significance.Methods A total of 45 CHB patients including 23 mild-to-moderate CHB patients,22severe CHB patients,and 15 healhy control cytometry

  12. Cord Blood Derived CD4+CD25high T Cells Become Functional Regulatory T Cells upon Antigen Encounter

    Science.gov (United States)

    Mayer, Elisabeth; Bannert, Christina; Gruber, Saskia; Klunker, Sven; Spittler, Andreas; Akdis, Cezmi A.

    2012-01-01

    Background: Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these “excessive” responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself. Methods: Cord blood (>37 week of gestation) and peripheral blood (healthy controls) were obtained and different Treg cell subsets were isolated. The suppressive potential of Treg populations after antigen exposure was evaluated via functional inhibition assays ([3H]thymidine incorporation assay and CFSE staining) with or without allergen stimulation. The frequency and markers of CD4+CD25highFoxP3+ T cells were characterized by mRNA analysis and flow cytometry. Results: Cord blood derived CD4+CD25high cells did not show substantial suppressor capacity upon TCR activation, in contrast to CD4+CD25high cells freshly purified from adult blood. This could not be explained by a lower frequency of FoxP3+CD4+CD25highcells or FOXP3 mRNA expression. However, after antigen-specific stimulation in vitro, these cells showed strong proliferation and expansion and gained potent suppressive properties. The efficiency of their suppressive capacity can be enhanced in the presence of endotoxins. If T-cells were sorted according to their CD127 expression, a tiny subset of Treg cells (CD4+CD25+CD127low) is highly suppressive even without prior antigen exposure. Conclusion: Cord blood harbors a very small subset of CD4+CD25high Treg cells that requires antigen-stimulation to show expansion and become functional suppressive Tregs. PMID:22272233

  13. The roles of blood-derived macrophages and resident microglia in the neuroinflammatory response to implanted Intracortical microelectrodes

    Science.gov (United States)

    Ravikumar, Madhumitha; Sunil, Smrithi; Black, James; Barkauskas, Deborah S.; Haung, Alex Y.; Miller, Robert H.; Selkirk, Stephen M.; Capadona, Jeffrey R.

    2014-01-01

    Resident microglia and blood-borne macrophages have both been implicated to play a dominant role in mediating the neuroinflammatory response affecting implanted intracortical microelectrodes. However, the distinction between each cell type has not been demonstrated due to a lack of discriminating cellular markers. Understanding the subtle differences of each cell population in mediating neuroinflammation can aid in determining the appropriate therapeutic approaches to improve microelectrode performance. Therefore, the goal of this study is to characterize the role of infiltrating blood-derived cells, specifically macrophages, in mediating neuroinflammation following intracortical microelectrode implantation. Interestingly, we found no correlation between microglia and neuron populations at the microelectrode-tissue interface. On the other hand, blood-borne macrophages consistently dominated the infiltrating cell population following microelectrode implantation. Most importantly, we found a correlation between increased populations of blood-derived cells (including the total macrophage population) and neuron loss at the microelectrode-tissue interface. Specifically, the total macrophage population was greatest at two and sixteen weeks post implantation, at the same time points when we observed the lowest densities of neuronal survival in closest proximity to the implant. Together, our results suggest a dominant role of infiltrating macrophages, and not resident microglia, in mediating neurodegeneration following microelectrode implantation. PMID:24973296

  14. Are globoseries glycosphingolipids SSEA-3 and -4 markers for stem cells derived from human umbilical cord blood?

    Institute of Scientific and Technical Information of China (English)

    Heli Suila; Jari Natunen; Saara Laitinen; Leena Valmu; Virve Pitk(a)nen; Tia Hirvonen; Annamari Heiskanen; Heidi Anderson; Anita Laitinen; Suvi Natunen; Halina Miller-Podraza; Tero Satomaa

    2011-01-01

    Umbilical cord blood (UCB) is an efficient and valuable source of hematopoietic stem cells (HSCs) for transplantation. In addition to HSCs it harbours low amounts of mesenchymal stem cells (MSCs). No single marker to identify cord blood-derived stem cells, or to indicate their multipotent phenotype, has been characterized so far. SSEA-3 and -4 are cell surface globoseries glycosphingolipid epitopes that are commonly used as markers for human embryonic stem cells, where SSEA-3 rapidly disappears when the cells start to differentiate. Lately SSEA-3 and -4 have also been observed in MSCs. As there is an ongoing discussion and variation of stem-cell markers between laboratories, we have now comprehensively characterized the expression of these epitopes in both the multipotent stem-cell types derived from UCB. We have performed complementary analysis using gene expression analysis, mass spectrometry and immunochemical methods, including both flow cytometry and immunofluoresence microscopy. SSEA-4, but not SSEA-3, was expressed on MSCs but absent from HSCs. Our findings indicate that SSEA-3 and/or -4 may not be optimal markers for multipotency in the case of stem cells derived from cord blood, as their expression may be altered by cell-culture conditions.

  15. Namibia's transition from whole blood-derived pooled platelets to single-donor apheresis platelet collections

    NARCIS (Netherlands)

    Pitman, John P.; Basavaraju, Sridhar V.; Shiraishi, Ray W.; Wilkinson, Robert; von Finckenstein, Bjorn; Lowrance, David W.; Marfin, Anthony A.; Postma, Maarten; Mataranyika, Mary; Smit Sibinga, Cees Th.

    2015-01-01

    BACKGROUNDFew African countries separate blood donations into components; however, demand for platelets (PLTs) is increasing as regional capacity to treat causes of thrombocytopenia, including chemotherapy, increases. Namibia introduced single-donor apheresis PLT collections in 2007 to increase PLT

  16. Characterization of the attachment mechanisms of tissue-derived cell lines to blood-compatible polymers.

    Science.gov (United States)

    Hoshiba, Takashi; Nikaido, Mayo; Tanaka, Masaru

    2014-05-01

    Recent advances in biomedical engineering require the development of new types of blood-compatible polymers that also allow non-blood cell attachment for the isolation of stem cells and circulating tumor cells (CTCs) from blood and for the development of artificial organs for use under blood-contact conditions. Poly(2-methoxyethyl acrylate) (PMEA) and poly(tetrafurfuryl acrylate) (PTHFA) were previously identified as blood-compatible polymers. Here, it is demonstrated that cancer cells can attach to the PMEA and PTHFA substrates, and the differences in the attachment mechanisms to the PMEA and PTHFA substrates between cancer cells and platelets are investigated. It is also found that the adsorption-induced deformation of fibrinogen, which is required for the attachment and activation of platelets, does not occur on the PMEA and PTHFA substrates. In contrast, fibronectin is deformed on the PMEA and PTHFA substrates. Therefore, it is concluded that cancer cells and not platelets can attach to the PMEA and PTHFA substrates based on this protein-deformation difference between these substrates. Moreover, it is observed that cancer cells attach to the PMEA substrate via both integrin-dependent and -independent mechanisms and attach to the PTHFA substrate only through an integrin-dependent mechanism. It is expected that PMEA and PTHFA will prove useful for blood-contact biomedical applications.

  17. Non-viral liposome-mediated transfer of brain-derived neurotrophic factor across the blood-brain barrier

    Institute of Scientific and Technical Information of China (English)

    Ying Xing; Chun-yan Wen; Song-tao Li; Zong-xin Xia

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in the repair of central nervous system injury, but cannot directly tra-verse the blood-brain barrier. Liposomes are a new type of non-viral vector, able to carry macromolecules across the blood-brain barrier and into the brain. Here, we investigate whether BDNF could be transported across the blood-brain barrier by tail-vein injection of lipo-somes conjugated to transferrin (Tf) and polyethylene glycol (PEG), and carrying BDNF modiifed with cytomegalovirus promoter (pCMV) or glial ifbrillary acidic protein promoter (pGFAP) (Tf-pCMV-BDNF-PEG and Tf-pGFAP-BDNF-PEG, respectively). Both liposomes were able to traverse the blood-brain barrier, and BDNF was mainly expressed in the cerebral cortex. BDNF expression in the cerebral cortex was higher in the Tf-pGFAP-BDNF-PEG group than in the Tf-pCMV-BDNF-PEG group. This study demonstrates the successful construction of a non-virus targeted liposome, Tf-pGFAP-BDNF-PEG, which crosses the blood-brain barrier and is distributed in the cerebral cortex. Our work provides an experimental basis for BDNF-related targeted drug delivery in the brain.

  18. Non-viral liposome-mediated transfer of brain-derived neurotrophic factor across the blood-brain barrier

    Directory of Open Access Journals (Sweden)

    Ying Xing

    2016-01-01

    Full Text Available Brain-derived neurotrophic factor (BDNF plays an important role in the repair of central nervous system injury, but cannot directly traverse the blood-brain barrier. Liposomes are a new type of non-viral vector, able to carry macromolecules across the blood-brain barrier and into the brain. Here, we investigate whether BDNF could be transported across the blood-brain barrier by tail-vein injection of liposomes conjugated to transferrin (Tf and polyethylene glycol (PEG, and carrying BDNF modified with cytomegalovirus promoter (pCMV or glial fibrillary acidic protein promoter (pGFAP (Tf-pCMV-BDNF-PEG and Tf-pGFAP-BDNF-PEG, respectively. Both liposomes were able to traverse the blood-brain barrier, and BDNF was mainly expressed in the cerebral cortex. BDNF expression in the cerebral cortex was higher in the Tf-pGFAP-BDNF-PEG group than in the Tf-pCMV-BDNF-PEG group. This study demonstrates the successful construction of a non-virus targeted liposome, Tf-pGFAP-BDNF-PEG, which crosses the blood-brain barrier and is distributed in the cerebral cortex. Our work provides an experimental basis for BDNF-related targeted drug delivery in the brain.

  19. Blood Conservation Strategies and Liver Transplantation Transfusion-Free Techniques Derived from Jehovah's Witness Surgical Cohorts.

    Science.gov (United States)

    Sheth, Mansi; Kulkarni, Sujit; Dhanireddy, Kiran; Perez, Alexander; Selby, Rick

    2015-01-01

    Red blood cell and component transfusions are a frequent and widely accepted accompaniment of surgical procedures. Although the risk of specific disease transmission via allogeneic blood transfusions (ABT) is very low, the occurrence of transfusion related immune modulation (TRIM) still remains a ubiquitous concern. Recent studies have shown that ABT are linked to increased morbidity and mortality across various specialties, with negative outcomes directly correlated to number of transfusions. Blood conservation methods are therefore necessary to reduce ABT. Acute normo-volemic hemodilution (ANH) along with pre-operative blood augmentation and intraoperative cell salvage are blood conservation techniques utilized in tertiary and even quaternary (transplantation) surgery in Jehovah's Witnesses with excellent outcomes. The many hematologic complications such as anemia, thrombocytopenia and coagulopathies that occur with liver transplantation present a significant barrier when trying to avoid ABT. Despite this, living donor liver transplantation (LDLT) has been successfully performed in a transfusion-free environment, providing valuable insight into the possibilities of limiting ABT and its associated risks in all patients.

  20. [Effect of phytic acid and its derivatives on blood lipid peroxidation state in vitro].

    Science.gov (United States)

    Martusevich, A K; Sidorova, M V; Mel'nikova, N B; Solov'eva, A G; Peretiagin, S P

    2014-01-01

    We have studied specific features of lipid peroxidation in whole human blood under the action of aqueous solutions of xymedone (19.6 microM), phytic acid (117.9 microM) and its complex (237.6 microM) synthesized in distilled water and isotonic (0.9%) solution of sodium chloride. The estimated parameters included lipid peroxidation (LPO) rate, total antioxidant potential, superoxide dismutase (SOD) level, and malonic dialdehyde (MDA) level in blood plasma and erythrocytes. It was established that the effect of phytic acid on blood samples includes moderate stimulation of total antioxidant activity and SOD activity with predominant prooxidant effect. The phytic acid--xymedone complex synthesized in distilled water exhibits an antioxidant action, while its synthesis in saline solution yields a prooxidant.

  1. Differentiating of banked human umbilical cord blood-derived mesenchymal stem cells into insulin-secreting cells.

    Science.gov (United States)

    Phuc, Pham Van; Nhung, Truong Hai; Loan, Dang Thi Tung; Chung, Doan Chinh; Ngoc, Phan Kim

    2011-01-01

    Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) are multipotent cells. They are able to differentiate into functional cells from not only mesoderm but also endoderm. Many researches showed that cells derived from fresh human UCB could transdifferentiate into insulin-secreting cells. In this study, transdifferentiating potential of cryopreserved human UCB-derived MSCs into insulin-secreting cell was investigated. Fresh human UCB was enriched the mononuclear cells by Ficoll-Paque centrifugation. The mononuclear cell population was cryopreserved in cryo-medium containing Iscove's modified Dulbecco's media (IMDM) with 10% DMSO at -196°C for 1 yr. After thawing, mononuclear cells were cultured to isolate MSCs in medium IMDM with 20% FBS supplemented with growth factors. At the fifth passages, MSCs were confirmed by flow cytometry about expression of CD13, CD14, CD34, CD45, CD166, and HLA-DR markers; after that, they were induced to differentiate into adipocytes and osteoblasts. After inducing with specific medium for islet differentiation, there were many clusters of cell like islet at day 14-28. Using real-time reverse transcription polymerase chain reaction (RT-PCR) to analyze the expression of functional genes, the result showed that Nestin, Pdx-1, Ngn3, Ils-1, Pax6, Pax4, Nkx2.2, Nkx6.1, Glut-2, Insulin genes expressed. The results showed that MSCs derived from banked cord blood can differentiate into functional pancreatic islet-like cells in vitro. If human MSCs, especially MSCs from banked cord blood of diabetes patients themselves can be isolated, proliferated, differentiated into functional pancreatic islet-like cells, and transplanted back into them (autologous transplantation), their high-proliferation potency and rejection avoidance will provide one promising therapy for diabetes.

  2. Characterization of Adherent Nonhematopoietic Cells Derived from Human Umbilical Cord Blood

    Institute of Scientific and Technical Information of China (English)

    安小惠; 蔡国平

    2003-01-01

    To confirm and characterize the adherent fibroblast-like progenitors in human umbilical cord blood, we isolated mononuclear cells from human umbilical cord blood by Ficoll-Hypaque.Two main morphologically different kinds of cells were formed by culturing the cells in collagen-coated 24-well plastic dishes and flasks.One type was the adherent fibroblast-like cells, while the other was loosely adherent clonally expanded round cells.Our experiments demonstrate that the adherent fibroblast-like cells possess multilineage potential, including the ability to differentiate into endothelial-like cells and to express the mesenchymal cell marker.

  3. Thermogenesis, blood metabolites and hormones, and growth of lambs born to ewes supplemented with algae-derived docosahexaenoic acid.

    Science.gov (United States)

    Keithly, J I; Kott, R W; Berardinelli, J G; Moreaux, S; Hatfield, P G

    2011-12-01

    Neonatal lamb mortality is a major factor affecting profitability in the sheep industry, and lamb thermogenesis is a key element in neonatal lamb survival. Increased lamb vigor has been reported when ewes were supplemented during late gestation with algae-derived docosahexaenoic acid (DHA); however, the effects of DHA on lamb thermogenesis and immunocompetence have not been investigated. Eighty twin-bearing Targhee ewes (ages 2 to 5 yr; 68.5 ± 3 kg) were assigned randomly to 1 of 2 supplement treatments to determine the effects of feeding DHA to ewes during late gestation and early lactation on lamb thermogenesis, serum metabolites and hormones, and lamb growth. Supplement treatments were 12 g·ewe(-1)·d(-1) of algae-derived DHA (DHA Gold Advanced Bionutrition Corp., Columbia, MD; algae-derived DHA); and no algae-derived DHA (control). Supplements were individually fed daily during the last 30 d (±7 d) of gestation and pen fed (6 pens/treatment with 6 or 7 ewes/pen) during the first 38 d (±7 d) of lactation. One hour after lambing and before nursing, twin-born lambs were weighed, blood sampled via jugular puncture, and placed in a dry cold chamber for 30 min (0°C), and rectal temperatures were recorded every minute for 30 min. Lambs were removed from the cold chamber, blood sampled, warmed for 15 min, and returned to their dam. Ewes were blood sampled, and colostrum samples were collected 1 h postpartum. Ewe and lamb sera were assayed for glucose, NEFA, cortisol, and leptin. Lamb rectal temperature, glucose, NEFA, cortisol, leptin, and birth weights did not differ between treatments. The BW at 38 d was greater (P = 0.03) for lambs born to control ewes than for lambs born to algae-derived DHA-supplemented ewes; however, the colostrum of algae-derived DHA-supplemented ewes had a greater specific gravity (P = 0.05) than for control ewes. Overall, despite a potentially positive effect on ewe colostral IgG concentrations, supplementation of algae-derived DHA during

  4. Identification of bovine material in porcine spray-dried blood derivatives using the Polymerase Chain Reaction technique

    Directory of Open Access Journals (Sweden)

    Sánchez A.

    2004-01-01

    Full Text Available Due to the widely supported theory of bovine spongiform encephalopathy (BSE spread in cattle by contaminated animal feeds, screening of feed products has become essential. For many years, manufacturers have used blood and plasma proteins as high quality ingredients of foods for both pets and farm animals. However, in Europe, the Commission Regulation 1234/2003/EC temporally bans the use of processed animal proteins, including blood-derivative products, in feedstuffs for all farm animals which are fattened or bred for the production of food. This regulation has some exceptions, such as the use of non ruminant blood products into the feed of farm fish. Authorization of the re-introduction of these proteins into animal feed formulations, especially non ruminant proteins into the feed for non ruminant farm animals, is expected when adequate control methods to discriminate ruminant proteins exist. Currently, the number of validated methods to differentiate the species of origin for most of the animal by-products is limited. Here we report the development of a rapid and sensitive polymerase chain reaction (PCR-based assay, which allows detection of bovine or porcine specific mitochondrial DNAfrom spray-dried blood derivate products (plasma, whole blood and red cells, as a marker for bovine contamination in porcine products. Sample extracts, suitable for PCR, were easily and quickly obtained with the commercial PrepManTM Ultra reagent (Applied Biosystems. To confirm the porcine origin of the samples, primers targeting a specific region of 134 bp of the porcine cytochrome b coding sequence were designed (cytbporc1-F and cytbporc2-R. Previously published PCR primers (L8129 and H8357, specific for a 271 bp fragment of the bovine mitochondrial ATPase 8-ATPase 6 genes, were chosen to accomplish amplification of bovine DNA. The limit of detection (LOD of the bovine PCR assay was at least of 0.05% (v/v of bovine inclusion in spray-dried porcine plasma or red

  5. Deriving a blood-mimicking fluid for particle image velocimetry in Sylgard-184 vascular models.

    Science.gov (United States)

    Yousif, Majid Y; Holdsworth, David W; Poepping, Tamie L

    2009-01-01

    A new blood-mimicking fluid (BMF) has been developed for particle image velocimetry (PIV), which enables flow studies in vascular models (phantoms). A major difficulty in PIV that affects measurement accuracy is the refraction and distortion of light passing through the interface between the model and the fluid, due to the difference in refractive index (n) between the two materials. The problem can be eliminated by using a fluid with a refractive index matching that of the model. Such fluids are not commonly available, especially for vascular research where the fluid should also have a viscosity similar to human blood. In this work, a blood-mimicking fluid, composed of water (47.38% by weight), glycerol (36.94% by weight) and sodium iodide salt (15.68% by weight), was developed for compatibility with our silicone (Sylgard 184; n = 1.414) phantoms. The fluid exhibits a dynamic viscosity of 4.31+/-0.03 cP which lies within the range of human blood viscosity (4.4+/-0.6 cP). Both refractive index and viscosity were attained at 22.2+/-0.2 degrees C, which is a feasible room temperature, thus eliminating the need for a temperature-control system. The fluid will be used to study hemodynamics in vascular flow models fabricated from Sylgard 184.

  6. Measurement of anterior and posterior circulation flow contributions to cerebral blood flow. An ultrasound-derived volumetric flow analysis.

    Science.gov (United States)

    Boyajian, R A; Schwend, R B; Wolfe, M M; Bickerton, R E; Otis, S M

    1995-01-01

    Ultrasound-derived volumetric flow analysis may be useful in answering questions of basic physiological interest in the cerebrovascular circulation. Using this technique, the authors have sought to describe quantitatively the complete concurrent flow relations among all four arteries supplying the brain. The aim of this study of normal subjects was to determine the relative flow contributions of the anterior (internal carotid arteries) and posterior (vertebral arteries) cerebral circulation. Comparisons between the observed and theoretically expected anterior and posterior flow distribution would provide an opportunity to assess traditional rheological conceptions in vivo. Pulsed color Doppler ultrasonography was used to measure mean flow rates in the internal carotid and vertebral arteries in 21 normal adults. The anterior circulation (internal carotid arteries bilaterally) carried 82% of the brain's blood supply and comprised 67% of the total vascular cross-sectional area. These values demonstrate precise concordance between observations in vivo and the theoretically derived (Hagen-Poiseuille) expected flow distribution. These cerebrovascular findings support the traditional conception of macroscopic blood flow. Further studies using ultrasound-derived volumetric analysis of the brain's arterial flow relations may illuminate the vascular pathophysiology underlying aging, cerebral ischemia, and dementias.

  7. Some biochemical parameters of blood plasma of turkey-hens following administration of 1,2,4-triasole derivative.

    Science.gov (United States)

    Krauze, M; Truchliński, J; Cendrowska-Pinkosz, M

    2007-01-01

    The present study involved 180 slaughter turkey-hens of heavy Big-6 type divided into four groups (in triplicate repetition for 15 birds). All the birds were fed with the same standard full-dose mixtures in 5-stage system. The turkey-hens of groups I, II and III were given 1,2,4-triasole derivative (3-(2-pyridil)-4-phenyl-1,2,4-triasole-5-carboxylic acid), which has antibacterial, antifungal and immunomodulating properties, in amount of 50, 75 and 100 microg per 1 dm3 of water. Group IV--control was given water without the additive. The 1,2,4-triasole derivative was given to drinking water, starting from the first day of bird's life and for the whole rearing period. The present results of biochemical analysis of blood plasma showed that addition of examined substance significantly reduced concentration of protein, glucose, triglycerides and uric acid as compared to control. It was stated that tested 1,2,4-triasole derivative elevated the level of HDL fraction percentage and alkaline phosphatase activity in blood plasma.

  8. Human cord blood derived immature basophils show dual characteristics, expressing both basophil and eosinophil associated proteins

    OpenAIRE

    Jeanette Grundström; Jenny M Reimer; Sofia E Magnusson; Gunnar Nilsson; Sara Wernersson; Lars Hellman

    2012-01-01

    Basophils are blood cells of low abundance associated with allergy, inflammation and parasite infections. To study the transcriptome of mature circulating basophils cells were purified from buffy coats by density gradient centrifugations and two-step magnetic cell sorting. However, after extensive analysis the cells were found to be transcriptionally inactive and almost completely lack functional mRNA. In order to obtain transcriptionally active immature basophils for analysis of their transc...

  9. Human Blood-Vessel-Derived Stem Cells for Tissue Repair and Regeneration

    Directory of Open Access Journals (Sweden)

    Chien-Wen Chen

    2012-01-01

    Full Text Available Multipotent stem/progenitor cells with similar developmental potentials have been independently identified from diverse human tissue/organ cultures. The increasing recognition of the vascular/perivascular origin of mesenchymal precursors suggested blood vessels being a systemic source of adult stem/progenitor cells. Our group and other laboratories recently isolated multiple stem/progenitor cell subsets from blood vessels of adult human tissues. Each of the three structural layers of blood vessels: intima, media, and adventitia has been found to include at least one precursor population, that is, myogenic endothelial cells (MECs, pericytes, and adventitial cells (ACs, respectively. MECs and pericytes efficiently regenerate myofibers in injured and dystrophic skeletal muscles as well as improve cardiac function after myocardial infarction. The applications of ACs in vascular remodeling and angiogenesis/vasculogenesis have been examined. Our recent finding that MECs and pericytes can be purified from cryogenically banked human primary muscle cell culture further indicates their potential applications in personalized regenerative medicine.

  10. Phenotypic and functional characteristics of dendritic cells derived from human peripheral blood monocytes

    Institute of Scientific and Technical Information of China (English)

    TANG Ling-ling; ZHANG Zhe; ZHENG Jie-sheng; SHENG Ji-fang; LIU Ke-zhou

    2005-01-01

    Objective: This study is aimed at developing a simple and easy way to generate dendritic cells (DCs) from human peripheral blood monocytes (PBMCs) in vitro. Methods: PBMCs were isolated directly from white blood cell rather than whole blood and purified by patching methods (collecting the attached cell and removing the suspension cell). DCs were then generated by culturing PBMCs for six days with 30 ng/ml recombinant human granulocyte-macrophage stimulating factor (rhGM-CSF) and 20 ng/ml recombinant human interleukin-4 (rhIL-4) in vitro. On the sixth day, TNF-alpha (TNFα) 30 ng/ml was added into some DC cultures, which were then incubated for two additional days. The morphology was monitored by light microscopy and transmission electronic microscopy, and the phenotypes were determined by flow cytometry. Autologous mixed leukocyte reactions (MLR) were used to characterize DC function after TNFα or lipopolysaccharide (LPS) stimulations for 24 h. Results: After six days of culture, the monocytes developed significant dendritic morphology and a portion of cells expressed CD 1 a, CD80 and CD86, features of DCs. TNFα treatment induced DCs maturation and up-regulation of CD80, CD86 and CD83. Autologous MLR demonstrated that these DCs possess potent T-cell stimulatory capacity. Conclusion: This study developed a simple and easy way to generate DCs from PBMCs exposed to rhGM-CSF and rhIL-4. The DCs produced by this method acquired morphologic and antigenic characteristics of DCs.

  11. Production of good manufacturing practice-grade human umbilical cord blood-derived mesenchymal stem cells for therapeutic use.

    Science.gov (United States)

    Van Pham, Phuc; Phan, Ngoc Kim

    2015-01-01

    Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) are multipotent stem cells that can be differentiated into several specific cell types such as adipocytes, osteoblasts, and chondroblasts. They also were demonstrated to trans-differentiate into other cell lineages such as muscle cells and neurons. Thus, they are considered a promising stem cell source for therapeutic use. Here, we describe a method for production of good manufacturing practice-grade human UCB-MSCs for therapeutic use. The obtained UCB-MSCs are free of allogenous or xenogenous proteins. In addition, these MSCs could maintain the MSC phenotype in long-term culture.

  12. Chondrogenic potential of mesenchymal stromal cells derived from equine bone marrow and umbilical cord blood

    DEFF Research Database (Denmark)

    Berg, Lise Charlotte; Koch, Thomas Gadegaard; Heerkens, T.

    2009-01-01

    Objective: Orthopaedic injury is the most common cause of lost training days or premature retirement in the equine athlete. Cell-based therapies are a potential new treatment option in musculo-skeletal diseases. Mesenthymal stromal cells (MSC) have been derived from multiple sources in the horse...

  13. Blood platelet-derived microparticles release and bubble formation after an open-sea air dive.

    Science.gov (United States)

    Pontier, Jean-Michel; Gempp, Emmanuel; Ignatescu, Mihaela

    2012-10-01

    Bubble-induced platelet aggregation offers an index for evaluating decompression severity in humans and in a rat model of decompression sickness. Endothelial cells, blood platelets, or leukocytes shed microparticles (MP) upon activation and during cell apoptosis. The aim was to study blood platelet MP (PMP) release and bubble formation after a scuba-air dive in field conditions. Healthy, experienced divers were assigned to 1 experimental group (n = 10) with an open-sea air dive to 30 msw for 30 min and 1 control group (n = 5) during head-out water immersion for the same period. Bubble grades were monitored with a pulsed doppler according to Kissman Integrated Severity Score (KISS). Blood samples for platelet count (PC) and PMP (annexin V and CD41) were taken 1 h before and after exposure in both groups. The result showed a decrease in post-dive PC compared with pre-dive values in experimental group with no significant change in the control group. We observed a significant increase in PMP values after the dive while no change was revealed in the control group. There was a significant positive correlation between the PMP values after the dive and the KISS bubble score. The present study highlighted a relationship between the post-dive decrease in PC, platelet MP release, and bubble formation. Release of platelet MPs could reflect bubble-induced platelet aggregation and could play a key role in alteration of the coagulation. Further studies must investigate endothelial and leukocyte MP release in the same field conditions.

  14. Sympathetic nerve-derived ATP regulates renal medullary blood flow via vasa recta pericytes

    Directory of Open Access Journals (Sweden)

    Scott S Wildman

    2013-10-01

    Full Text Available Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta, and therefore may be able to regulate medullary blood flow (MBF. Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesise that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is

  15. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources

    Science.gov (United States)

    Lippmann, Ethan S.; Al-Ahmad, Abraham; Azarin, Samira M.; Palecek, Sean P.; Shusta, Eric V.

    2014-02-01

    Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm2). Overall, this scalable human BBB model may enable a wide range of neuroscience studies.

  16. Functional and Pharmacological Analysis of Cardiomyocytes Differentiated from Human Peripheral Blood Mononuclear-Derived Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Michael Riedel

    2014-07-01

    Full Text Available Advances in induced pluripotent stem cell (iPSC technology have set the stage for routine derivation of patient- and disease-specific human iPSC-cardiomyocyte (CM models for preclinical drug screening and personalized medicine approaches. Peripheral blood mononuclear cells (PBMCs are an advantageous source of somatic cells because they are easily obtained and readily amenable to transduction. Here, we report that the electrophysiological properties and pharmacological responses of PBMC-derived iPSC CM are generally similar to those of iPSC CM derived from other somatic cells, using patch-clamp, calcium transient, and multielectrode array (MEA analyses. Distinct iPSC lines derived from a single patient display similar electrophysiological features and pharmacological responses. Finally, we demonstrate that human iPSC CMs undergo acute changes in calcium-handling properties and gene expression in response to rapid electrical stimulation, laying the foundation for an in-vitro-tachypacing model system for the study of human tachyarrhythmias.

  17. Functional and pharmacological analysis of cardiomyocytes differentiated from human peripheral blood mononuclear-derived pluripotent stem cells.

    Science.gov (United States)

    Riedel, Michael; Jou, Chuanchau J; Lai, Shuping; Lux, Robert L; Moreno, Alonso P; Spitzer, Kenneth W; Christians, Elizabeth; Tristani-Firouzi, Martin; Benjamin, Ivor J

    2014-07-08

    Advances in induced pluripotent stem cell (iPSC) technology have set the stage for routine derivation of patient- and disease-specific human iPSC-cardiomyocyte (CM) models for preclinical drug screening and personalized medicine approaches. Peripheral blood mononuclear cells (PBMCs) are an advantageous source of somatic cells because they are easily obtained and readily amenable to transduction. Here, we report that the electrophysiological properties and pharmacological responses of PBMC-derived iPSC CM are generally similar to those of iPSC CM derived from other somatic cells, using patch-clamp, calcium transient, and multielectrode array (MEA) analyses. Distinct iPSC lines derived from a single patient display similar electrophysiological features and pharmacological responses. Finally, we demonstrate that human iPSC CMs undergo acute changes in calcium-handling properties and gene expression in response to rapid electrical stimulation, laying the foundation for an in-vitro-tachypacing model system for the study of human tachyarrhythmias.

  18. Generation of highly purified human cardiomyocytes from peripheral blood mononuclear cell-derived induced pluripotent stem cells.

    Science.gov (United States)

    Fuerstenau-Sharp, Maya; Zimmermann, Martina E; Stark, Klaus; Jentsch, Nico; Klingenstein, Melanie; Drzymalski, Marzena; Wagner, Stefan; Maier, Lars S; Hehr, Ute; Baessler, Andrea; Fischer, Marcus; Hengstenberg, Christian

    2015-01-01

    Induced pluripotent stem (iPS) cells have an enormous potential for physiological studies. A novel protocol was developed combining the derivation of iPS from peripheral blood with an optimized directed differentiation to cardiomyocytes and a subsequent metabolic selection. The human iPS cells were retrovirally dedifferentiated from activated T cells. The subsequent optimized directed differentiation protocol yielded 30-45% cardiomyocytes at day 16 of differentiation. The derived cardiomyocytes expressed appropriate structural markers like cardiac troponin T, α-actinin and myosin light chain 2 (MLC2V). In a subsequent metabolic selection with lactate, the cardiomyocytes content could be increased to more than 90%. Loss of cardiomyocytes during metabolic selection were less than 50%, whereas alternative surface antibody-based selection procedures resulted in loss of up to 80% of cardiomyocytes. Electrophysiological characterization confirmed the typical cardiac features and the presence of ventricular, atrial and nodal-like action potentials within the derived cardiomyocyte population. Our combined and optimized protocol is highly robust and applicable for scalable cardiac differentiation. It provides a simple and cost-efficient method without expensive equipment for generating large numbers of highly purified, functional cardiomyocytes. It will further enhance the applicability of iPS cell-derived cardiomyocytes for disease modeling, drug discovery, and regenerative medicine.

  19. Generation of highly purified human cardiomyocytes from peripheral blood mononuclear cell-derived induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Maya Fuerstenau-Sharp

    Full Text Available Induced pluripotent stem (iPS cells have an enormous potential for physiological studies. A novel protocol was developed combining the derivation of iPS from peripheral blood with an optimized directed differentiation to cardiomyocytes and a subsequent metabolic selection. The human iPS cells were retrovirally dedifferentiated from activated T cells. The subsequent optimized directed differentiation protocol yielded 30-45% cardiomyocytes at day 16 of differentiation. The derived cardiomyocytes expressed appropriate structural markers like cardiac troponin T, α-actinin and myosin light chain 2 (MLC2V. In a subsequent metabolic selection with lactate, the cardiomyocytes content could be increased to more than 90%. Loss of cardiomyocytes during metabolic selection were less than 50%, whereas alternative surface antibody-based selection procedures resulted in loss of up to 80% of cardiomyocytes. Electrophysiological characterization confirmed the typical cardiac features and the presence of ventricular, atrial and nodal-like action potentials within the derived cardiomyocyte population. Our combined and optimized protocol is highly robust and applicable for scalable cardiac differentiation. It provides a simple and cost-efficient method without expensive equipment for generating large numbers of highly purified, functional cardiomyocytes. It will further enhance the applicability of iPS cell-derived cardiomyocytes for disease modeling, drug discovery, and regenerative medicine.

  20. Umbilical Cord Blood-Derived Stem Cells Improve Heat Tolerance and Hypothalamic Damage in Heat Stressed Mice

    Directory of Open Access Journals (Sweden)

    Ling-Shu Tseng

    2014-01-01

    Full Text Available Heatstroke is characterized by excessive hyperthermia associated with systemic inflammatory responses, which leads to multiple organ failure, in which brain disorders predominate. This definition can be almost fulfilled by a mouse model of heatstroke used in the present study. Unanesthetized mice were exposed to whole body heating (41.2°C for 1 hour and then returned to room temperature (26°C for recovery. Immediately after termination of whole body heating, heated mice displayed excessive hyperthermia (body core temperature ~42.5°C. Four hours after termination of heat stress, heated mice displayed (i systemic inflammation; (ii ischemic, hypoxic, and oxidative damage to the hypothalamus; (iii hypothalamo-pituitary-adrenocortical axis impairment (reflected by plasma levels of both adrenocorticotrophic-hormone and corticosterone; (iv decreased fractional survival; and (v thermoregulatory deficits (e.g., they became hypothermia when they were exposed to room temperature. These heatstroke reactions can be significantly attenuated by human umbilical cord blood-derived CD34+ cells therapy. Our data suggest that human umbilical cord blood-derived stem cells therapy may improve outcomes of heatstroke in mice by reducing systemic inflammation as well as hypothalamo-pituitary-adrenocortical axis impairment.

  1. Histone deacetylase inhibition enhances self renewal and cardioprotection by human cord blood-derived CD34 cells.

    Directory of Open Access Journals (Sweden)

    Ilaria Burba

    Full Text Available BACKGROUND: Use of peripheral blood- or bone marrow-derived progenitors for ischemic heart repair is a feasible option to induce neo-vascularization in ischemic tissues. These cells, named Endothelial Progenitors Cells (EPCs, have been extensively characterized phenotypically and functionally. The clinical efficacy of cardiac repair by EPCs cells remains, however, limited, due to cell autonomous defects as a consequence of risk factors. The devise of "enhancement" strategies has been therefore sought to improve repair ability of these cells and increase the clinical benefit. PRINCIPAL FINDINGS: Pharmacologic inhibition of histone deacetylases (HDACs is known to enhance hematopoietic stem cells engraftment by improvement of self renewal and inhibition of differentiation in the presence of mitogenic stimuli in vitro. In the present study cord blood-derived CD34(+ were pre-conditioned with the HDAC inhibitor Valproic Acid. This treatment affected stem cell growth and gene expression, and improved ischemic myocardium protection in an immunodeficient mouse model of myocardial infarction. CONCLUSIONS: Our results show that HDAC blockade leads to phenotype changes in CD34(+ cells with enhanced self renewal and cardioprotection.

  2. Novel approach for deriving genome wide SNP analysis data from archived blood spots

    Directory of Open Access Journals (Sweden)

    Fowler Katie E

    2012-09-01

    Full Text Available Abstract Background The ability to transport and store DNA at room temperature in low volumes has the advantage of optimising cost, time and storage space. Blood spots on adapted filter papers are popular for this, with FTA (Flinders Technology Associates Whatman™TM technology being one of the most recent. Plant material, plasmids, viral particles, bacteria and animal blood have been stored and transported successfully using this technology, however the method of porcine DNA extraction from FTA Whatman™TM cards is a relatively new approach, allowing nucleic acids to be ready for downstream applications such as PCR, whole genome amplification, sequencing and subsequent application to single nucleotide polymorphism microarrays has hitherto been under-explored. Findings DNA was extracted from FTA Whatman™TM cards (following adaptations of the manufacturer’s instructions, whole genome amplified and subsequently analysed to validate the integrity of the DNA for downstream SNP analysis. DNA was successfully extracted from 288/288 samples and amplified by WGA. Allele dropout post WGA, was observed in less than 2% of samples and there was no clear evidence of amplification bias nor contamination. Acceptable call rates on porcine SNP chips were also achieved using DNA extracted and amplified in this way. Conclusions DNA extracted from FTA Whatman cards is of a high enough quality and quantity following whole genomic amplification to perform meaningful SNP chip studies.

  3. Proteomic Profiling of Ex Vivo Expanded CD34-Positive Haematopoetic Cells Derived from Umbilical Cord Blood

    Directory of Open Access Journals (Sweden)

    Heiner Falkenberg

    2013-01-01

    Full Text Available Ex vivo expansion of haematopoetic cells by application of specific cytokines is one approach to overcome boundaries in cord blood transplantation due to limited numbers of haematopoetic stem cells. While many protocols describe an effective increase of total cell numbers and the amount of CD34-positive cells, it still remains unclear if and how the procedure actually affects the cells’ properties. In the presented publications, CD34-positive cells were isolated from cord blood and expanded for up to 7 days in media supplemented with stem cell factor (SCF, thrombopoietin (THPO, interleukin 6 (IL-6, and fms-related tyrosine kinase 3 ligand (FLT3lg. At days 3 and 7, expanded cells were harvested and analyzed by flow cytometry and quantitative proteomics. 2970 proteins were identified, whereof proteomic analysis showed 440 proteins significantly changed in abundance during ex vivo expansion. Despite the fact that haematopoetic cells still expressed CD34 on the surface after 3 days, major changes in regard to the protein profile were observed, while further expansion showed less effect on the proteome level. Enrichment analysis of biological processes clearly showed a proteomic change toward a protein biosynthesis phenotype already within the first three days of expression.

  4. A REVIEW ON EFFECTIVE APPLICATION OF AN ENAMEL MATRIX DERIVATIVE (EMDOGAIN® FOR PERIODONTAL SURGERY IN THE PRESENCE OF BLOOD

    Directory of Open Access Journals (Sweden)

    Oana M. CALUSERU

    2013-06-01

    Full Text Available Reconstructive periodontal surgery aims at predictably restoring tooth’s supporting structure lost due to perio‐ dontal disease or trauma. One such modality, which has been demonstrate to promote periodontal regeneration, is an enamel matrix derivative (EMD, consisting of a formu‐ lation of amelogenin proteins from developing porcine enamel. This review article provides a brief update on the effects of blood interaction, occurring during periodontal surgery, on the effectiveness of EMD adsorption on the root surfaces and its implications for periodontal recon‐ structive surgery.The clinical use of an enamel matrix derivative (EMD has been successfully proved in periodontal surgery, as promoting regeneration of periodontal tissues including new cementum, periodontal ligament (PDL and alveolar bone [1]. Despite its widespread use, only recently has the effect of blood, occurring during periodontal surgery, been evaluated for contamination of the effectiveness of EMD adsorption onto root surfaces. The aim of this review arti‐ cle is to provide the clinician a summary of findings from in vitro experiments testing the effects of EMD adsorption onto root surfaces in the presence and absence of blood and its effect on PDL cell behavior [2]. Until recently, the extent to which bleeding occurring during periodontal sur‐ gery affects the adsorption of EMD onto root surfaces could not be established.In summary, the teeth extracted for orthodontic reasons were subject to ex vivo scaling and root planing and expo‐ sed to 6 clinically relevant scenarios, as illustrated in figure 1. EMD application is usually performed following root surface conditioning with 24% EDTA. Findings from high resolution scanning electron microscopy (SEM demons‐ trated that the proteins found in blood (mainly albumin were able to compete with those found in EMD (Figure 2, reducing the effectiveness of EMD thereafter. No apparent effect of conditioning the surface

  5. Identification of myeloid derived suppressor cells in the peripheral blood of tumor bearing dogs

    OpenAIRE

    Sherger Matthew; Kisseberth William; London Cheryl; Olivo-Marston Susan; Papenfuss Tracey L

    2012-01-01

    Abstract Background Myeloid derived suppressor cells (MDSCs) are a recently described population of immune cells that significantly contribute to the immunosuppression seen in cancer patients. MDSCs are one of the most important factors that limit the efficacy of cancer immunotherapy (e.g. cancer vaccines) and MDSC levels are increased in cancer in multiple species. Identifying and targeting MDSCs is actively being investigated in the field of human oncology and is increasingly being investig...

  6. Isolation of mesenchymal stem cells from equine umbilical cord blood

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Heerkens, Tammy; Thomsen, Preben Dybdahl

    2007-01-01

    Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non......-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low......, for the first time, the isolation of mesenchymal-like stem cells from fresh equine cord blood and their differentiation into osteocytes, chondrocytes and adipocytes. This novel isolation of equine cord blood MSCs and their preliminary in vitro differentiation positions the horse as the ideal pre-clinical animal...

  7. Near-infrared spectroscopy and indocyanine green derived blood flow index for noninvasive measurement of muscle perfusion during exercise.

    Science.gov (United States)

    Habazettl, Helmut; Athanasopoulos, Dimitris; Kuebler, Wolfgang M; Wagner, Harrieth; Roussos, Charis; Wagner, Peter D; Ungruhe, Juergen; Zakynthinos, Spyros; Vogiatzis, Ioannis

    2010-04-01

    Near-infrared spectroscopy (NIRS) with the tracer indocyanine green (ICG) may be used for measuring muscle blood flow (MBF) during exercise, if arterial ICG concentration is measured simultaneously. Although pulse dye densitometry allows for noninvasive measurement of arterial dye concentration, this technique is sensitive to motion and may not be applicable during exercise. The aim of this study was to evaluate a noninvasive blood flow index (BFI), which is derived solely from the muscle ICG concentration curve. In 10 male cyclists 5 mg ICG were injected into an antecubital vein at rest and during cycling at 30, 60, 70, 80, 90, and 100% of previously determined maximal work load. Simultaneously blood was withdrawn through a photodensitometer at 20 ml/min from the radial artery to measure arterial ICG concentration. To measure muscle tissue ICG concentrations, two sets of NIRS optodes were positioned on the skin, one over the left seventh intercostal space and the other over the left vastus lateralis muscle. MBF was calculated from the arterial and muscle concentration data according to Fick's principle. BFI was calculated solely from the muscle concentration curve as ICG concentration difference divided by rise time between 10 and 90% of peak. During exercise mean BFI values changed similarly to MBF in both intercostal and quadriceps muscles and showed excellent correlations with MBF: r = 0.98 and 0.96, respectively. Individual data showed some scattering among BFI and MBF values but still reasonable correlations of BFI with MBF: r = 0.73 and 0.72 for intercostal and quadriceps muscles, respectively. Interobserver variability, as analyzed by Bland-Altman plots, was considerably less for BFI than MBF. These data suggest that BFI can be used for measuring changes in muscle perfusion from rest to maximal exercise. Although absolute blood flow cannot be determined, BFI has the advantages of being essentially noninvasive and having low interobserver variability.

  8. Intestinal Microbiota-Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

    Energy Technology Data Exchange (ETDEWEB)

    Ó Broin, Pilib [Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Department of Mathematical Sciences, Yeshiva University, New York, New York (United States); Vaitheesvaran, Bhavapriya [Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Saha, Subhrajit [Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Hartil, Kirsten [Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Chen, Emily I. [Department of Pharmacology, Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York (United States); Goldman, Devorah; Fleming, William Harv [Department of Medicine, Oregon Health and Science University, Portland, Oregon (United States); Kurland, Irwin J. [Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Guha, Chandan, E-mail: cguha@montefiore.org [Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Golden, Aaron, E-mail: aaron.golden@einstein.yu.edu [Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Department of Mathematical Sciences, Yeshiva University, New York, New York (United States)

    2015-02-01

    Purpose: Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials: Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative, untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results: We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusions: Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma.

  9. Glycomic analysis of sialic acid linkages in glycans derived from blood serum glycoproteins.

    Science.gov (United States)

    Alley, William R; Novotny, Milos V

    2010-06-04

    A number of alterations to the normal glycomic profile have been previously described for a number of diseases and disorders, thus underscoring the medical importance of studying the glycans associated with proteins present in biological samples. An important alteration in cancer progression is an increased level of alpha2,6-sialylation, which aids in increasing the metastatic potential of tumor cells. Here we report a glycomic method that selectively amidates alpha2,6-linked sialic acids, while those that are alpha2,3-linked undergo spontaneous lactonization. Following subsequent permethylation, MALDI-TOF MS analysis revealed that many sialylated glycans present on glycoproteins found in blood serum featured increased levels of alpha2,6-sialylation in breast cancer samples. On the basis of the altered ratios of alpha2,3-linked to alpha2,6-linked sialic acids, many of these glycans became diagnostically relevant when they did not act as such indicators when based on traditional glycomic profiling alone.

  10. Generation of feline dendritic cells derived from peripheral blood monocytes for in vivo use.

    Science.gov (United States)

    Freer, Giulia; Matteucci, Donatella; Mazzetti, Paola; Bozzacco, Leonia; Bendinelli, Mauro

    2005-10-01

    Dendritic cells (DCs) are professional antigen-presenting cells that can prime T cells and polarize the cellular immune response. Because Th1-type immune responses have been connected to success in combating viral infection, a promising therapeutic application of DCs would be their differentiation in vitro and injection back into the host to boost an immune response in infected animals. This study was aimed both at developing a protocol to cultivate feline DCs in the absence of exogenous proteins for their use in vivo and at investigating what might be the most appropriate stimulus to induce their maturation in vitro and finding correlates of maturation. We generated DCs from peripheral blood monocytes in the presence of feline interleukin-4 and granulocyte-macrophage colony stimulating factor, and after 5 days their maturation was induced with either lipopolysaccharide, human recombinant tumor necrosis factor alpha, poly(I:C), or activated feline platelets. After 48 h, their CD14, CD1a, major histocompatibility complex class II, and B7.1 surface expression was analyzed in parallel with their ability to uptake antigen or prime a mixed leukocyte reaction. The results presented show that feline DCs cultured in autologous plasma differentiate and are able to mature in the presence of stimuli similar to the ones currently used for other species. The present work sets the grounds for future use of DCs obtained by the protocol described for in vivo vaccination and immunotherapy of feline immunodeficiency virus-infected cats.

  11. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue.

    Science.gov (United States)

    Heo, June Seok; Choi, Youjeong; Kim, Han-Soo; Kim, Hyun Ok

    2016-01-01

    Mesenchymal stem cells (MSCs) are clinically useful due to their capacity for self-renewal, their immunomodulatory properties and tissue regenerative potential. These cells can be isolated from various tissues and exhibit different potential for clinical applications according to their origin, and thus comparative studies on MSCs from different tissues are essential. In this study, we investigated the immunophenotype, proliferative potential, multilineage differentiation and immunomodulatory capacity of MSCs derived from different tissue sources, namely bone marrow, adipose tissue, the placenta and umbilical cord blood. The gene expression profiles of stemness-related genes [octamer-binding transcription factor 4 (OCT4), sex determining region Y-box (SOX)2, MYC, Krüppel-like factor 4 (KLF4), NANOG, LIN28 and REX1] and lineage‑related and differentiation stage-related genes [B4GALNT1 (GM2/GS2 synthase), inhibin, beta A (INHBA), distal-less homeobox 5 (DLX5), runt-related transcription factor 2 (RUNX2), proliferator‑activated receptor gamma (PPARG), CCAAT/enhancer-binding protein alpha (C/EBPA), bone morphogenetic protein 7 (BMP7) and SOX9] were compared using RT-PCR. No significant differences in growth rate, colony-forming efficiency and immunophenotype were observed. Our results demonstrated that MSCs derived from bone marrow and adipose tissue shared not only in vitro tri-lineage differentiation potential, but also gene expression profiles. While there was considerable inter-donor variation in DLX5 expression between MSCs derived from different tissues, its expression appears to be associated with the osteogenic potential of MSCs. Bone marrow-derived MSCs (BM-MSCs) significantly inhibited allogeneic T cell proliferation possibly via the high levels of the immunosuppressive cytokines, IL10 and TGFB1. Although MSCs derived from different tissues and fibroblasts share many characteristics, some of the marker genes, such as B4GALNT1 and DLX5 may be useful for

  12. Phenotype and function of myeloid dendritic cells derived from African green monkey blood monocytes.

    Science.gov (United States)

    Mortara, Lorenzo; Ploquin, Mickaël J-Y; Faye, Abdourahmane; Scott-Algara, Daniel; Vaslin, Bruno; Butor, Cécile; Hosmalin, Anne; Barré-Sinoussi, Françoise; Diop, Ousmane M; Müller-Trutwin, Michaela C

    2006-01-20

    Myeloid dendritic cells probably play an important role in the immune response against HIV and SIV, and in the enhancement of CD4+ T cell infection. Here, we have investigated phenotypic and functional features of myeloid monocyte-derived DC (MDDC) from African green monkeys (AGMs). AGMs are natural hosts of SIV and exhibit no signs of abnormal T cell activation despite high SIV plasma viremia. We identified mAbs that cross-react specifically with homologous molecules expressed on AGM DC. We adapted a protocol to derive AGM MDDC by culture in the presence of GM-CSF and IL-4. The differentiated cells possessed a typical dendritic morphology and the majority were CD11c+ DC-SIGN+. AGM MDDC displayed a high expression of typical maturation markers, such as CD83, CD86 and DC-LAMP, and moderate immunostimulatory capacity, suggesting that the cells were in a semi-mature state. Stimulation resulted in further maturation, as shown by up-regulation of CD80 and decrease of endocytosis ability. However, neither increase of HLA-DR or CD40 expression nor enhanced immunostimulatory capacity was observed. The latter was associated with a low pro-inflammatory cytokine production during mixed lymphocyte reactions and a cytokine balance in favour of IL-10 in contrast to human MDDC. This is the first characterization of AGM MDDC. The tools described here are a crucial step for future studies in vivo or in vitro on the function of myeloid DC using the AGM animal model.

  13. Advances in menstrual blood-derived stem cells%宫内膜干细胞研究进展

    Institute of Scientific and Technical Information of China (English)

    张金龙; 张舒琪; 袁立

    2012-01-01

    本文介绍新型间充质干细胞—宫内膜干细胞的来源和特征,简述宫内膜干细胞分离、培养和体外扩增的方法;阐述宫内膜干细胞体外诱导分化心肌细胞和神经细胞的潜能,展望宫内膜干细胞的临床应用价值.%Menstrual blood-derived stem cells (MenSCs) are newly discovered mesenchymal stem cells. They have the potential ability to differentiate into various cell types, including heart and nerve cells. MenSCs provide an alternative source of adult stem cells for research and use in regenerative medicine.

  14. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Chang, Jong Wook [Research Institute for Future Medicine Stem Cell and Regenerative Medicine Center, Samsung Medical Center, Seoul 137-710 (Korea, Republic of); Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Kim, Jae-Sung [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-709 (Korea, Republic of); Jeon, Hong Bae, E-mail: jhb@medi-post.co.kr [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of)

    2014-04-18

    Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications.

  15. Coxsackievirus B4 Can Infect Human Peripheral Blood-Derived Macrophages

    Directory of Open Access Journals (Sweden)

    Enagnon Kazali Alidjinou

    2015-11-01

    Full Text Available Beyond acute infections, group B coxsackieviruses (CVB are also reported to play a role in the development of chronic diseases, like type 1 diabetes. The viral pathogenesis mainly relies on the interplay between the viruses and innate immune response in genetically-susceptible individuals. We investigated the interaction between CVB4 and macrophages considered as major players in immune response. Monocyte-derived macrophages (MDM generated with either M-CSF or GM-CSF were inoculated with CVB4, and infection, inflammation, viral replication and persistence were assessed. M-CSF-induced MDM, but not GM-CSF-induced MDM, can be infected by CVB4. In addition, enhancing serum was not needed to infect MDM in contrast with parental monocytes. The expression of viral receptor (CAR mRNA was similar in both M-CSF and GM-CSF MDM. CVB4 induced high levels of pro-inflammatory cytokines (IL-6 and TNFα in both MDM populations. CVB4 effectively replicated and persisted in M-CSF MDM, but IFNα was produced in the early phase of infection only. Our results demonstrate that CVB4 can replicate and persist in MDM. Further investigations are required to determine whether the interaction between the virus and MDM plays a role in the pathogenesis of CVB-induced chronic diseases.

  16. [Risk Assessment of Single-Donor (Apheresis) Platelet Concentrates and Pooled Whole-Blood-Derived Platelet Concentrates].

    Science.gov (United States)

    Hitzler, Walter; Hutschenreuter, Gabriele; Wartensleben, Herbert

    2015-01-01

    According to the risk estimates of the Robert-Koch-Institute (RKI) and the Paul Ehrlich-Institute (PEI) an equivalence cannot be assumed to exist between the two different platelet preparations. Differences between single-donor (apheresis) platelet concentrates (ATK) and pooled whole-blood-derived platelet concentrates (PTK) result from donor populations, donation intervals, and preparation techniques. There are no prospective randomized studies with regard to the clinical efficacy, which would unambiguously demonstrate equivalence of the therapeutic efficacy of PTK (buffy coat method) in comparison to ATK. The German Association of Blood Transfusion Services (StKB) points out that, due to the non-equivalence of PTK and ATK, it is incumbent on the transfusion physician to select the platelet concentrate, make the appropriate disclosures, and assume treatment responsibility. Proper compensation for ATK and PTK must be ensured by the health insurance companies, whereby a special indication for the selection of either PTK or ATK is not given. Exceptions are patients with known HLA antibodies in which only selected platelet concentrates may be administered. Otherwise, no indication exists in the selection of the different platelet concentrates (Article is in German).

  17. Human umbilical cord blood derived mesenchymal stem cells were differentiated into pancreatic endocrine cell by Pdx-1 electrotransfer

    Directory of Open Access Journals (Sweden)

    Phuoc Thi-My Nguyen

    2014-02-01

    Full Text Available Diabetes mellitus type 1 is an autoimmune disease with high incidence in adolescents and young adults. A seductive approach overcomes normally obstacles treatment is cell-replacement therapy to endogenous insulin production. At the present, to get enough pancreatic endocrine cells (PECs in cell transplantation, differentiation of mesenchymal stem cells (MSCs into IPCs is an interesting and promising strategy. This study aimed to orient umbilical cord blood-derived MSCs (UCB-MSCs to PECs by Pdx-1 electrotransfer. UCB-MSCs were isolated from human umbilical cord blood according to published protocol. Pdx-1 was isolated and cloned into a plasmid vector. Optimal voltage of an electrotransfer was investigated to improve the cell viability and gene transfection efficacy. The results showed that 200V of the electrotransfer significantly increased in the efficiency of electrotransfer and survival cells compared with other high voltages (350V and 550V. Pdx-1 successfully transfected UCB-MSCs over-expressed pancreatic related genes as Ngn3, Nkx6.1. These results suggested that Pdx-1 transfected UCB-MSCs were successfully oriented PECs. Different to lentiviral vectors, electrotransfer is a safer method to transfer Pdx-1 to UCB-MSCs and a useful tool in translational research. [Biomed Res Ther 2014; 1(2.000: 50-56

  18. Osteogenic potential of human umbilical cord-derived mesenchymal stromal cells cultured with umbilical cord blood-derived fibrin: a preliminary study.

    Science.gov (United States)

    Baba, Kyoko; Yamazaki, Yasuharu; Ishiguro, Masashi; Kumazawa, Kenichi; Aoyagi, Kazuya; Ikemoto, Shigehiro; Takeda, Akira; Uchinuma, Eiju

    2013-12-01

    This study examined the potential for osteogenesis via regenerative medicine using autologous tissues (umbilical cord (UC) and umbilical cord blood (UCB)) in nude mice. The study was designed to provide the three elements required for regenerative medicine (cell, scaffold, and growth factor) and autoserum for culture by means of autologous tissues. Mesenchymal stromal cells were obtained from UC (UC-MSCs). Fibrin, platelet-rich-plasma, and autoserum were obtained from UCB as scaffold, growth factor and serum for culture respectively. UC-MSCs were obtained from Wharton jelly and cultured with UCB-derived fibrin (UCB-fibrin) for 3-4 weeks to induce their differentiation into osteoblasts. They were implanted subcutaneously into the dorsum of male nude mice for 6 weeks prior to undergoing assessment. The assessments performed were haematoxylin and eosin, and alizarin red staining, immunohistochemical staining of human mitochondria, scanning electron microscopy, scanning electron microscopy with energy dispersive X-ray spectrometry and real-time reverse transcriptase-polymerase chain reaction to assess the expressions of osteoblast markers. Consequently, the differentiation of UC-MSCs into osteoblasts and the production of hydroxyapatite were verified. This study suggested the possible formation of bone tissue using biomedical materials obtained from UC and UCB.

  19. A Novel Molecular and Functional Stemness Signature Assessing Human Cord Blood-Derived Endothelial Progenitor Cell Immaturity.

    Directory of Open Access Journals (Sweden)

    Oriane Guillevic

    Full Text Available Endothelial Colony Forming Cells (ECFCs, a distinct population of Endothelial Progenitor Cells (EPCs progeny, display phenotypic and functional characteristics of endothelial cells while retaining features of stem/progenitor cells. Cord blood-derived ECFCs (CB-ECFCs have a high clonogenic and proliferative potentials and they can acquire different endothelial phenotypes, this requiring some plasticity. These properties provide angiogenic and vascular repair capabilities to CB-ECFCs for ischemic cell therapies. However, the degree of immaturity retained by EPCs is still confused and poorly defined. Consequently, to better characterize CB-ECFC stemness, we quantified their clonogenic potential and demonstrated that they were reprogrammed into induced pluripotent stem cells (iPSCs more efficiently and rapidly than adult endothelial cells. Moreover, we analyzed the transcriptional profile of a broad gene panel known to be related to stem cells. We showed that, unlike mature endothelial cells, CB-ECFCs expressed genes involved in the maintenance of embryonic stem cell properties such as DNMT3B, GDF3 or SOX2. Thus, these results provide further evidence and tools to appreciate EPC-derived cell stemness. Moreover this novel stem cell transcriptional signature of ECFCs could help better characterizing and ranging EPCs according to their immaturity profile.

  20. Partial purification of the 5-hydroxytryptophan-reuptake system from human blood platelets using a citalopram-derived affinity resin

    Energy Technology Data Exchange (ETDEWEB)

    Biessen, E.A.L; Horn, A.S.; Robillard, G.T. (Univ. of Groningen (Netherlands))

    1990-04-03

    This paper describes a procedure for the synthesis and application of a citalopram-derived affinity resin in purifying the 5HT-reuptake system from human blood platelets. A two-step scheme has been developed for partial purification, based on wheat germ agglutinin-lectin (WGA) affinity and citalopram affinity chromatographies. Upon solubilization of the carrier with 1% digitonin, a 50-70-fold increase in specific ({sup 3}H) imipramine binding activity with a 70% recovery could be accomplished through WGA-lectin chromatography. The WGA pool was then subjected to affinity chromatography on citalopram-agarose. At least 90% of the binding capacity adsorbed to the column. Specific elution using 10 {mu}M citalopram resulted in a 22% recovery of binding activity. A 10,000-fold overall purification was obtained by using this two-step procedure. Analysis of the fractions on SDS-PAGE after {sup 125}I labeling revealed specific elution of 78- and 55-kDa proteins concomitant with the appearance of ({sup 3}H) imipramine binding activity. The pharmacological profile of the partially purified reuptake system correlated well with that derived from the crude membrane-bound reuptake system, suggesting a copurification of the 5HT binding activity and ({sup 3}H)imipramine binding activity.

  1. Human umbilical cord blood-derived mesenchymal stromal cells display a novel interaction between P-selectin and galectin-1.

    Science.gov (United States)

    Suila, H; Hirvonen, T; Kotovuori, A; Ritamo, I; Kerkelä, E; Anderson, H; Natunen, S; Tuimala, J; Laitinen, S; Nystedt, J; Räbinä, J; Valmu, L

    2014-07-01

    Human multipotent mesenchymal stromal/stem cells (MSCs) have been shown to exert immunomodulatory properties that have great potential in therapies for various inflammatory and autoimmune disorders. However, intravenous delivery of these cells is followed by massive cell entrapment in the lungs and insufficient homing to target tissues or organs. In targeting to tissues, MSCs and other therapeutic cells employ similar mechanisms as leucocytes, including a cascade of rolling and adhesion steps mediated by selectins, integrins and their ligands. However, the mechanisms of MSCs homing are not well understood. We discovered that P-selectin (CD62P) binds to umbilical cord blood (UCB)-derived MSCs independently of the previously known sialyl Lewis x (sLex)-containing ligands such as P-selectin glycoprotein ligand-1 (PSGL-1, CD162). By biochemical assays, we identified galectin-1 as a novel ligand for P-selectin. Galectin-1 has previously been shown to be a key mediator of the immunosuppressive effects of human MSCs. We conclude that this novel interaction is likely to play a major role in the immunomodulatory targeting of human UCB-derived MSCs.

  2. Conditioned Media from Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Inhibits Melanogenesis by Promoting Proteasomal Degradation of MITF.

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    Eun Sung Kim

    Full Text Available Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs secrete various beneficial molecules, which have anti-apoptotic activity and cell proliferation. However, the effect of hUCB-MSCs in melanogenesis is largely unclear. In this study, we show that conditioned media (CM derived from hUCB-MSCs inhibit melanogenesis by regulating microphthalmia-associated transcription factor (MITF expression via the ERK signalling pathway. Treatment of hUCB-MSC-CM strongly inhibited the alpha-melanocyte stimulating hormone-induced hyperpigmentation in melanoma cells as well as melanocytes. Treatment of hUCB-MSC-CM induced ERK1/2 activation in melanocytes. In addition, inhibition of ERK1/2 suppressed the anti-pigmentation activity of the hUCB-MSC-CM in melanocytes and in vitro artificial skin models. We also found that the expression of MITF was appreciably diminished while expression of phosphorylated MITF, which leads to its proteasomal degradation, was increased in cells treated with hUCB-MSC-CM. These results suggested that hUCB-MSC-CM significantly suppresses melanin synthesis via MITF degradation by the ERK pathway activation.

  3. Absolute counts of peripheral blood leukocyte subpopulations in intraabdominal sepsis and pneumonia-derived sepsis: a pilot study Absolute counts of peripheral blood leukocyte subpopulations in intraabdominal sepsis and pneumonia-derived sepsis: a pilot study

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    Grazyna Anna Hoser

    2012-10-01

    Full Text Available The leading pathophysiological changes during sepsis include systemic abnormalities in the immune
    response. Due to the general character of these disturbances, sepsis is usually studied as a homogenous clinical
    condition. We aimed to compare the immune response in intraabdominal sepsis (IAS and pneumonia-derived
    sepsis (PDS. The following cell populations were examined: white blood cell count (WBC, monocytes, lymphocytes:
    CD3+, CD4+ and CD8+ T cells, B cells, and NK cells. In both studied groups (i.e. IAS and PDS, the
    WBC was elevated. However, it was significantly higher in the IAS group than in the PDS group. The difference
    was due to a lower granulocyte count, as well as a lower monocyte count in PDS. We found no significant
    correlation between the total lymphocyte number and CD3+CD8+ T cells in either form of sepsis. Similarly, we
    observed no correlation between the total lymphocyte number and the NK cells subset in IAS. However, the
    numbers of CD3+CD8+ and NK cells correlated similarly in both types of sepsis. Both studied types of sepsis
    induced profound lymphocytopenia, with marked loss of CD8+ T cells and the NK cells. However, the similar
    relation between them, which was independent of the infection type, suggests that the NK and CD3+CD8+ cells
    have shared mechanisms of regulation. The primary site of infection has an impact on the global immune reaction.
    These alternations include especially myeloid cells: granulocytes and monocytes which disappear from peripheral
    blood during PDS, but increase in IAS.
    The leading pathophysiological changes during sepsis include systemic abnormalities in the immune
    response. Due to the general character of these disturbances, sepsis is usually studied as a homogenous clinical
    condition. We aimed to compare the immune response in intraabdominal sepsis (IAS and pneumonia-derived
    sepsis (PDS. The following cell

  4. Distribution of blood derivatives by registered blood establishments that qualify as health care entities; Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; delay of applicability date. Final rule; delay of applicability date.

    Science.gov (United States)

    2006-11-13

    The Food and Drug Administration (FDA) is further delaying, until December 1, 2008, the applicability date of a certain requirement of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720) (the final rule). The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The provisions of the final rule became effective on December 4, 2000, except for certain provisions whose effective or applicability dates were delayed in five subsequent Federal Register notices, until December 1, 2006. The provision with the delayed applicability date would prohibit wholesale distribution of blood derivatives by registered blood establishments that meet the definition of a "health care entity." In the Federal Register of February 1, 2006 (71 FR 5200), FDA published a proposed rule specific to the distribution of blood derivatives by registered blood establishments that qualify as health care entities (the proposed rule). The proposed rule would amend certain limited provisions of the final rule to allow certain registered blood establishments that qualify as health care entities to distribute blood derivatives. In response to the proposed rule, FDA received substantive comments. As explained in the SUPPLEMENTARY INFORMATION section of this document, further delaying the applicability of Sec. 203.3(q) (21 CFR 203.3(q)) to the wholesale distribution of blood derivatives by health care entities is necessary to give the agency additional time to address comments on the proposed rule, consider whether regulatory changes are appropriate, and, if so, to initiate such changes.

  5. Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells.

    Science.gov (United States)

    Balan, Sreekumar; Ollion, Vincent; Colletti, Nicholas; Chelbi, Rabie; Montanana-Sanchis, Frédéric; Liu, Hong; Vu Manh, Thien-Phong; Sanchez, Cindy; Savoret, Juliette; Perrot, Ivan; Doffin, Anne-Claire; Fossum, Even; Bechlian, Didier; Chabannon, Christian; Bogen, Bjarne; Asselin-Paturel, Carine; Shaw, Michael; Soos, Timothy; Caux, Christophe; Valladeau-Guilemond, Jenny; Dalod, Marc

    2014-08-15

    Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1(+) DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1(+) human DC. Assessment of the immunoactivation potential of XCR1(+) human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1(+) and XCR1(-) human DC in CD34(+) progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR1(-) CD34-DC are similar to canonical MoDC, whereas XCR1(+) CD34-DC resemble XCR1(+) blood DC (bDC). XCR1(+) DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1(+) DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1(+) CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1(+) bDC. Hence, it is feasible to generate high numbers of bona fide XCR1(+) human DC in vitro as a model to decipher the functions of XCR1(+) bDC and as a potential source of XCR1(+) DC for clinical use.

  6. Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

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    Biaoru Li

    Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

  7. Comparative evaluation of differentiation potential of menstrual blood- versus bone marrow-derived stem cells into hepatocyte-like cells.

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    Sayeh Khanjani

    Full Text Available Menstrual blood has been introduced as an easily accessible and refreshing stem cell source with no ethical consideration. Although recent works have shown that menstrual blood stem cells (MenSCs possess multi lineage differentiation capacity, their efficiency of hepatic differentiation in comparison to other stem cell resources has not been addressed so far. The aim of this study was to investigate hepatic differentiation capacity of MenSCs compared to bone marrow-derived stem cells (BMSCs under protocols developed by different concentrations of hepatocyte growth factor (HGF and oncostatin M (OSM in combination with other components in serum supplemented or serum-free culture media. Such comparison was made after assessment of immunophenotye, trans-differentiation potential, immunogenicity and tumorigeicity of these cell types. The differential expression of mature hepatocyte markers such as albumin (ALB, cytokeratin 18 (CK-18, tyrosine aminotransferase and cholesterol 7 alpha-hydroxylase activities (CYP7A1 at both mRNA and protein levels in differentiating MenSCs was significantly higher in upper concentration of HGF and OSM (P1 compared to lower concentration of these factors (P2. Moreover, omission of serum during differentiation process (P3 caused typical improvement in functions assigned to hepatocytes in differentiated MenSCs. While up-regulation level of ALB and CYP7A1 was higher in differentiated MenSCs compared to driven BMSCs, expression level of CK-18, detected level of produced ALB and glycogen accumulation were lower or not significantly different. Therefore, based on the overall comparable hepatic differentiation ability of MenSCs with BMSCs, and also accessibility, refreshing nature and lack of ethical issues of MenSCs, these cells could be suggested as an apt and safe alternative to BMSCs for future stem cell therapy of chronic liver diseases.

  8. In Vivo Efficacy of Umbilical Cord Blood Stem Cell-Derived NK Cells in the Treatment of Metastatic Colorectal Cancer

    Science.gov (United States)

    Veluchamy, John P.; Lopez-Lastra, Silvia; Spanholtz, Jan; Bohme, Fenna; Kok, Nina; Heideman, Daniëlle A. M.; Verheul, Henk M. W.; Di Santo, James P.; de Gruijl, Tanja D.; van der Vliet, Hans J.

    2017-01-01

    Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RASwt metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK). While cetuximab monotherapy was not effective against EGFR− RASwt, EGFR+ RASmut, and EGFR+ BRAFmut cells, A-PBNK were able to initiate lysis of EGFR+ colon cancer cells irrespective of RAS or BRAF status. Cytotoxic effects of A-PBNK (but not UCB-NK) were further potentiated significantly by coating EGFR+ colon cancer cells with cetuximab. Of note, a significantly higher cytotoxicity was induced by UCB-NK in EGFR−RASwt (42 ± 8 versus 67 ± 7%), EGFR+ RASmut (20 ± 2 versus 37 ± 6%), and EGFR+ BRAFmut (23 ± 3 versus 43 ± 7%) colon cancer cells compared to A-PBNK and equaled the cytotoxic efficacy of the combination of A-PBNK and cetuximab. The antitumor efficacy of UCB-NK cells against cetuximab-resistant human EGFR+ RASmut colon cancer cells was further confirmed in an in vivo preclinical mouse model where UCB-NK showed enhanced antitumor cytotoxicity against colon cancer independent of EGFR and RAS status. As UCB-NK have been proven safe in a recently conducted phase I clinical trial in acute myeloid leukemia, a fast translation into clinical proof of concept for mCRC could be considered. PMID:28220124

  9. Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and renin angiotensin system.

    Science.gov (United States)

    Mattace Raso, Giuseppina; Pirozzi, Claudio; d'Emmanuele di Villa Bianca, Roberta; Simeoli, Raffaele; Santoro, Anna; Lama, Adriano; Di Guida, Francesca; Russo, Roberto; De Caro, Carmen; Sorrentino, Raffaella; Calignano, Antonio; Meli, Rosaria

    2015-01-01

    Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF), and renin angiotensin system (RAS) modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day) for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the activation of

  10. Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and renin angiotensin system.

    Directory of Open Access Journals (Sweden)

    Giuseppina Mattace Raso

    Full Text Available Palmitoylethanolamide (PEA, a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR. Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF, and renin angiotensin system (RAS modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the

  11. Different chronological patterns of appearance of blood derived milk components during mastitis indicate different mechanisms of transfer from blood into milk.

    Science.gov (United States)

    Wellnitz, Olga; Zbinden, Christina; Lüttgenau, Johannes; Bollwein, Heinrich; Bruckmaier, Rupert M

    2015-08-01

    This study aimed to describe chronological patterns of changes of various candidate blood components in milk during the acute phase of a mammary immune response in detail. Eight dairy cows were challenged with Escherichia coli lipopolysaccharide in one udder quarter. Milk from challenged and control quarters and blood samples were taken before, and 1 and 2 h after challenge and then every 15 min until 5 h after challenge. The SCC, serum albumin, immunoglobulin (Ig)G1, IgG2, lactate dehydrogenase (LDH), and L-lactate in milk and blood, and α-lactalbumin in blood were analysed. All selected parameters in milk increased in challenged quarters but did not increase in control quarters. Milk IgG1, IgG2, serum albumin, and LDH were already significantly increased at 2 h after challenge whereas a significant increase of SCC was detectable at 2.75 h and L-lactate was increased at 2.25 h after challenge. In blood L-lactate was increased at 3.75 h after challenge, however, other factors in blood did not change significantly within the 5 h of experiment. In conclusion, the increase of blood components in milk during inflammation follows two different patterns: There is a rapid increase for IgG1, IgG2, or LDH, before the increase of SCC, and their concentrations reach a plateau within 3 h. On the other hand, SCC and L-lactate show a slower but consistent increase not reaching a plateau within 5 h after LPS challenge. L-lactate increases to higher concentrations in milk than in blood. This clearly shows that the increase of blood components follows different patterns and is therefore a controlled and compound-specific process and not exclusively an unspecific type of leakage.

  12. Human Umbilical Cord Blood-Derived Serum for Culturing the Supportive Feeder Cells of Human Pluripotent Stem Cell Lines

    Directory of Open Access Journals (Sweden)

    Ruttachuk Rungsiwiwut

    2016-01-01

    Full Text Available Although human pluripotent stem cells (hPSCs can proliferate robustly on the feeder-free culture system, genetic instability of hPSCs has been reported in such environment. Alternatively, feeder cells enable hPSCs to maintain their pluripotency. The feeder cells are usually grown in a culture medium containing fetal bovine serum (FBS prior to coculture with hPSCs. The use of FBS might limit the clinical application of hPSCs. Recently, human cord blood-derived serum (hUCS showed a positive effect on culture of mesenchymal stem cells. It is interesting to test whether hUCS can be used for culture of feeder cells of hPSCs. This study was aimed to replace FBS with hUCS for culturing the human foreskin fibroblasts (HFFs prior to feeder cell preparation. The results showed that HFFs cultured in hUCS-containing medium (HFF-hUCS displayed fibroblastic features, high proliferation rates, short population doubling times, and normal karyotypes after prolonged culture. Inactivated HFF-hUCS expressed important genes, including Activin A, FGF2, and TGFβ1, which have been implicated in the maintenance of hPSC pluripotency. Moreover, hPSC lines maintained pluripotency, differentiation capacities, and karyotypic stability after being cocultured for extended period with inactivated HFF-hUCS. Therefore, the results demonstrated the benefit of hUCS for hPSCs culture system.

  13. Distribution of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in canines after intracerebroventricular injection.

    Science.gov (United States)

    Park, Sang Eon; Jung, Na-Yeon; Lee, Na Kyung; Lee, Jeongmin; Hyung, Brian; Myeong, Su Hyeon; Kim, Hyeong Seop; Suh, Yeon-Lim; Lee, Jung-Il; Cho, Kyung Rae; Kim, Do Hyung; Choi, Soo Jin; Chang, Jong Wook; Na, Duk L

    2016-11-01

    In this study, we investigated the distribution of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) administered via intracerebroventricular (ICV) injection in a canine model. Ten beagles (11-13 kg per beagle) each received an injection of 1 × 10(6) cells into the right lateral ventricle and were sacrificed 7 days after administration. Based on immunohistochemical analysis, hUCB-MSCs were observed in the brain parenchyma, especially along the lateral ventricular walls. Detected as far as 3.5 mm from the cortical surface, these cells migrated from the lateral ventricle toward the cortex. We also observed hUCB-MSCs in the hippocampus and the cervical spinal cord. According to real-time polymerase chain reaction results, most of the hUCB-MSCs were found distributed in the brain and the cervical spinal cord but not in the lungs, heart, kidneys, spleen, and liver. ICV administered hUCB-MSCs also enhanced the endogenous neural stem cell population in the subventricular zone. These results highlighted the ICV delivery route as an optimal route to be performed in stem cell-based clinical therapies for neurodegenerative diseases.

  14. Peripheral blood-derived bovine dendritic cells promote IgG1-restricted B cell responses in vitro.

    Science.gov (United States)

    Bajer, Anna A; Garcia-Tapia, David; Jordan, Kimberly R; Haas, Karen M; Werling, Dirk; Howard, Chris J; Estes, D Mark

    2003-01-01

    Regulation of humoral responses involves multiple cell types including the requirements for cognate interactions between T and B cells to drive CD40-dependent responses to T-dependent antigens. A third cell type has also been shown to play an essential role, the dendritic cell (DC). We demonstrate that bovine peripheral blood-derived (PB)-DC are similar in function to features described for human interstitial DC including the production of signature type 2 cytokines [interleukin (IL)-13, IL-10]. PB-DC express moderate-to-high costimulatory molecule expression, and major histocompatibility complex class II is negative for CD14 expression and has low or no expression of CD11c. Consistent with the interstitial phenotype is the ability of PB-DC to influence B cell activation and differentiation via direct expression of CD40L and type 2 cytokines. Collectively, these results suggest that direct B cell-DC interactions may promote an immunoglobulin-isotype expression pattern consistent with type 2 responses, independent of direct T cell involvement.

  15. Electrophysiological characterisation of human umbilical cord blood-derived mesenchymal stem cells induced by olfactory ensheathing cell-conditioned medium.

    Science.gov (United States)

    Zeng, Yu; Rong, Mingqiang; Liu, Yunsheng; Liu, Jingfang; Lu, Ming; Tao, Xiaoyu; Li, Zhenyan; Chen, Xin; Yang, Kui; Li, Chuntao; Liu, Zhixiong

    2013-12-01

    Umbilical cord blood-derived marrow stromal cells (UCB-MSCs) with high proliferation capacity and immunomodulatory properties are considered to be a good candidate for cell-based therapies. But until now, little work has been focused on the differentiation of UCB-MSCs. In this work, UCB-MSCs were demonstrated to be negative for CD34 and CD45 expression but positive for CD90 and CD105 expression. The gate values of UCB-MSCs for CD90 and CD105 were 99.3 and 98.6 %, respectively. Two weeks after treatment, the percentage of neuron-like cells differentiated from UCB-MSCs was increased to 84 ± 12 % in the experimental group [treated with olfactory ensheathing cells (OECs)-conditioned medium] and they were neuron-specific enolase positive; few neuron-like cells were found in the control group (without OECs-conditioned medium). Using whole-cell recording, sodium and potassium currents were recorded in UCB-MSCs after differentiation by OECs. Thus, human UCB-MSCs could be differentiated to neural cells by secreted secretion from OECs and exhibited electrophysiological properties similar to mature neurons after 2 weeks post-induction. These results imply that OECs can be used as a new strategy for stem cell differentiation and provide an alternative neurogenesis pathway for generating sufficient numbers of neural cells for cell therapy.

  16. Optimization of primary culture condition for mesenchymal stem cells derived from umbilical cord blood with factorial design.

    Science.gov (United States)

    Fan, Xiubo; Liu, Tianqing; Liu, Yang; Ma, Xuehu; Cui, Zhanfeng

    2009-01-01

    Mesenchymal stem cells (MSCs) can not only support the expansion of hematopoietic stem cells in vitro, but also alleviate complications and accelerate recovery of hematopoiesis during hematopoietic stem cell transplantation. However, it proved challenging to culture MSCs from umbilical cord blood (UCB) with a success rate of 20-30%. Many cell culture parameters contribute to this outcome and hence optimization of culture conditions is critical to increase the probability of success. In this work, fractional factorial design was applied to study the effect of cell inoculated density, combination and dose of cytokines, and presence of serum and stromal cells. The cultured UCB-MSC-like cells were characterized by flow cytometry and their multilineage differentiation potentials were tested. The optimal protocol was identified achieving above 90% successful outcome: 2 x 10(6) cells/mL mononuclear cells inoculated in Iscove's modified Dulbecco's medium supplied with 10% FBS, 15 ng/mL IL-3, and 5 ng/mL Granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, the UCB-MSC-like cells expressed MSC surface markers of CD13, CD29, CD105, CD166, and CD44 positively, and CD34, CD45, and human leukocyte antigens-DR (HLA-DR) negatively. Meanwhile, these cells could differentiate into osteoblasts, chondrocytes, and adipocytes similarly to MSCs derived from bone marrow. In conclusion, we have developed an efficient protocol for the primary culture of UCB-MSCs by adding suitable cytokines into the culture system.

  17. In vitro detection of contact allergens: development of an optimized protocol using human peripheral blood monocyte-derived dendritic cells.

    Science.gov (United States)

    Reuter, Hendrik; Spieker, Jochem; Gerlach, Silke; Engels, Ursula; Pape, Wolfgang; Kolbe, Ludger; Schmucker, Robert; Wenck, Horst; Diembeck, Walter; Wittern, Klaus-Peter; Reisinger, Kerstin; Schepky, Andreas G

    2011-02-01

    Allergic contact dermatitis is a delayed T-cell mediated allergic response associated with relevant social and economic impacts. Animal experiments (e.g. the local lymph node assay) are still supplying most of the data used to assess the sensitization potential of new chemicals. However, the 7th amendment to the EU Cosmetic Directive will introduce a testing ban for cosmetic ingredients after 2013. In vitro alternative methods are thus being actively developed. Although promising results have been obtained with cell lines, their reduced functionality and inherent genomic instability led us to reinvestigate the use of peripheral blood monocyte-derived dendritic cells (PBMDCs) for the establishment of a reliable in vitro sensitization test. To solve the issues associated with the use of primary cells, the culture and exposure conditions (cytokine concentrations, incubation time, readout, pooled vs. single donors and cytotoxicity) were re-assessed and optimized. Here we propose a stable and reproducible protocol based on PBMDCs. This should allow a wider acceptance of PBMDCs as a reliable test system for the detection of human skin sensitizers and the inclusion of this protocol in an integrated testing strategy.

  18. Histone Deacetylase (HDAC Inhibitors Down-Regulate Endothelial Lineage Commitment of Umbilical Cord Blood Derived Endothelial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Horia Maniu

    2012-11-01

    Full Text Available To test the involvement of histone deacetylases (HDACs activity in endothelial lineage progression, we investigated the effects of HDAC inhibitors on endothelial progenitors cells (EPCs derived from umbilical cord blood (UCB. Adherent EPCs, that expressed the endothelial marker proteins (PCAM-1, CD105, CD133, and VEGFR2 revealed by flow cytometry were treated with three HDAC inhibitors: Butyrate (BuA, Trichostatin A (TSA, and Valproic acid (VPA. RT-PCR assay showed that HDAC inhibitors down-regulated the expression of endothelial genes such as VE-cadherin, CD133, CXCR4 and Tie-2. Furthermore, flow cytometry analysis illustrated that HDAC inhibitors selectively reduce the expression of VEGFR2, CD117, VE-cadherin, and ICAM-1, whereas the expression of CD34 and CD45 remained unchanged, demonstrating that HDAC is involved in endothelial differentiation of progenitor cells. Real-Time PCR demonstrated that TSA down-regulated telomerase activity probably via suppression of hTERT expression, suggesting that HDAC inhibitor decreased cell proliferation. Cell motility was also decreased after treatment with HDAC inhibitors as shown by wound-healing assay. The balance of acethylation/deacethylation kept in control by the activity of HAT (histone acetyltransferases/HDAC enzymes play an important role in differentiation of stem cells by regulating proliferation and endothelial lineage commitment.

  19. Modulation of Sickle Red Blood Cell Adhesion and its Associated Changes in Biomarkers by Sulfated Nonanticoagulant Heparin Derivative.

    Science.gov (United States)

    Alshaiban, Abdulelah; Muralidharan-Chari, Vandhana; Nepo, Anne; Mousa, Shaker A

    2016-04-01

    Abnormal cellular adhesion is one of the primary causes of vaso-occlusive crisis in sickle cell disease (SCD). Levels of intercellular adhesion molecule 1 (ICAM-1) and P-selectin are upregulated, resulting in increased adhesion of leukocytes and sickle red blood cells (RBCs) to endothelium. This study compares the inhibitory effect of a sulfated nonanticoagulant heparin (S-NACH) derivative with a low-molecular-weight heparin, tinzaparin, on the adhesion of sickle RBCs to endothelium. The S-NACH exhibits minimum effects on hemostasis and bleeding and interferes with the binding of pancreatic cancer cells to endothelial cells via P-selectin. We show by static binding assay that pretreatment of both erythrocytes and endothelial cells with S-NACH significantly inhibits the increased adhesion of sickle RBCs to endothelial cells. The S-NACH treatment also decreases the higher plasma levels of (adhesion biomarkers) ICAM-1 and P-selectin in SCD mice. This investigation signals further research into the potential use of S-NACH in treating vaso-occlusions with minimal bleeding events in patients with SCD.

  20. Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model.

    Science.gov (United States)

    Park, Yong-Beom; Song, Minjung; Lee, Choong-Hee; Kim, Jin-A; Ha, Chul-Won

    2015-11-01

    This study was carried out to assess the feasibility of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in articular cartilage repair and to further determine a suitable delivering hydrogel in a rat model. Critical sized full thickness cartilage defects were created. The hUCB-MSCs and three different hydrogel composites (hydrogel A; 4% hyaluronic acid/30% pluronic (1:1, v/v), hydrogel B; 4% hyaluronic acid, and hydrogel C; 4% hyaluronic acid/30% pluronic/chitosan (1:1:2, v/v)) were implanted into the experimental knee (right knee) and hydrogels without hUCB-MSCs were implanted into the control knee (left knee). Defects were evaluated after 8 weeks. The hUCB-MSCs with hydrogels composites resulted in a better repair as seen by gross and histological evaluation compared with hydrogels without hUCB-MSCs. Among the three different hydrogels, the 4% hyaluronic acid hydrogel composite (hydrogel B) showed the best result in cartilage repair as seen by the histological evaluation compared with the other hydrogel composites (hydrogel A and C). The results of this study suggest that hUCB-MSCs may be a promising cell source in combination with 4% hyaluronic acid hydrogels in the in vivo repair of cartilage defects.

  1. Neuroprotective Effects of Transplanted Mesenchymal Stromal Cells-derived Human Umbilical Cord Blood Neural Progenitor Cells in EAE

    Directory of Open Access Journals (Sweden)

    Hassan Rafieemehr

    2015-11-01

    Full Text Available Multiple Sclerosis (MS is an autoimmune inflammatory demyelinating disease of the central nervous system. The aim of this study was to investigate the neuroprotective effects of transplanted human umbilical cord blood mesenchymal stromal cells (UCB-MSC derived neural progenitor cell (MDNPC in EAE, an experimental model of MS. To initiate neuronal differentiation of UCB-MSCs, the pre-induction medium was removed and replaced with induction media containing retinoic acid, b FGF, h EGF, NGF, IBMX and ascorbic acid for one week. The expression of neural genes was examined in comparison to control group by real-time PCR assay. Then, experimental autoimmune encephalitis (EAE was induced using myelin oligodendrocyte glycoprotein (MOG, 35-55 peptides in 24 C57BL/6 mice. After induction, the mice were divided in four groups (n=6 as follows: healthy, PBS, UCB-MSCs and MDNPC, respectively. At the end of the study, disease status in all the groups was analyzed using hematoxylin-eosin (H&E staining of brain sections. We found that UCB-MSCs exhibit neuronal differentiation potential in vitro and transplanted MDNPC lowered clinical score and reduced CNS leukocyte infiltration compared to untreated mice. Our results showed that MDNPC from UCB may be a proper candidate for regenerative therapy in MS and other neurodegenerative diseases. 

  2. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

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    Isaac Perea-Gil

    2015-01-01

    Full Text Available Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs. Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells.

  3. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

    Science.gov (United States)

    Perea-Gil, Isaac; Monguió-Tortajada, Marta; Gálvez-Montón, Carolina; Bayes-Genis, Antoni; Borràs, Francesc E.; Roura, Santiago

    2015-01-01

    Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs) with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs). Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ) was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells. PMID:25861626

  4. Plasma brain-derived neurotrophic factor and reverse dipping pattern of nocturnal blood pressure in patients with cardiovascular risk factors.

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    Manabu Kadoya

    Full Text Available Basic studies have shown that brain-derived neurotrophic factor (BDNF has critical roles in the survival, growth, maintenance, and death of central and peripheral neurons, while it is also involved in regulation of the autonomic nervous system. Furthermore, recent clinical studies have suggested potential role of plasma BDNF in the circulatory system.We investigated the mutual relationships among plasma BDNF, patterns of nocturnal blood pressure changes (dippers, non-dippers, extra-dippers, and reverse-dippers, and cardiac autonomic function as determined by heart rate variability (HRV.This was a cross-sectional study of patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA Study from October 2010 to November 2012.Two-hundred fifty patients with 1 or more cardiovascular risk factor(s (obesity, smoking, presence of cardiovascular event history, hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease were enrolled.Plasma BDNF levels (natural logarithm transformed were significantly (p = 0.001 lower in reverse-dipper patients (7.18±0.69 pg/ml, mean ± SD, n = 36 as compared to dippers (7.86±0.86 pg/ml, n = 100. Multiple logistic regression analysis showed that BDNF (odds ratios: 0.417, 95% confidence interval: 0.228-0.762, P = 0.004 was the sole factor significantly and independently associated with the reverse-dippers as compared with dippers. Furthermore, plasma BDNF level was significantly and positively correlated with the time-domain (SDNN, SDANN5, CVRR and frequency-domain (LF of HRV parameters. Finally, multiple logistic regression analyses showed that the relationship between plasma BDNF and the reverse-dippers was weakened, yet remained significant or borderline significant even after adjusting for HRV parameters.Low plasma BDNF was independently associated with patients showing a reverse-dipper pattern of nocturnal blood pressure, in which an imbalance of cardiac autonomic function

  5. Detection Limits for Blood on Fabrics Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy and Derivative Processing.

    Science.gov (United States)

    Lu, Zhenyu; DeJong, Stephanie A; Cassidy, Brianna M; Belliveau, Raymond G; Myrick, Michael L; Morgan, Stephen L

    2016-06-27

    Attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) was used to detect blood stains based on signature protein absorption in the mid-IR region, where intensity changes in the spectrum can be related to blood concentration. Partial least squares regression (PLSR) was applied for multivariate calibrations of IR spectra of blood dilutions on four types of fabric (acrylic, nylon, polyester, and cotton). Gap derivatives (GDs) were applied as a preprocessing technique to optimize the performance of calibration models. We report a much improved IR detection limit (DL) for blood on cotton (2700× in dilution factor units) and the first IR DL reported for blood on nylon (250×). Due to sample heterogeneity caused by fabric hydrophobicity, acrylic fabric produced variable ATR FT-IR spectra that caused poor DLs in concentration units compared to previous work. Polyester showed a similar problem at low blood concentrations that lead to a relatively poor DL as well. However, the increased surface sensitivity and decreased penetration depth of ATR FT-IR make it an excellent choice for detection of small quantities of blood on the front surface of all fabrics tested (0.0010 µg for cotton, 0.0077 µg for nylon, 0.011 µg for acrylic, and 0.0066 µg for polyester).

  6. Predicting Out-of-Office Blood Pressure in the Clinic (PROOF-BP): Derivation and Validation of a Tool to Improve the Accuracy of Blood Pressure Measurement in Clinical Practice.

    Science.gov (United States)

    Sheppard, James P; Stevens, Richard; Gill, Paramjit; Martin, Una; Godwin, Marshall; Hanley, Janet; Heneghan, Carl; Hobbs, F D Richard; Mant, Jonathan; McKinstry, Brian; Myers, Martin; Nunan, David; Ward, Alison; Williams, Bryan; McManus, Richard J

    2016-05-01

    Patients often have lower (white coat effect) or higher (masked effect) ambulatory/home blood pressure readings compared with clinic measurements, resulting in misdiagnosis of hypertension. The present study assessed whether blood pressure and patient characteristics from a single clinic visit can accurately predict the difference between ambulatory/home and clinic blood pressure readings (the home-clinic difference). A linear regression model predicting the home-clinic blood pressure difference was derived in 2 data sets measuring automated clinic and ambulatory/home blood pressure (n=991) using candidate predictors identified from a literature review. The model was validated in 4 further data sets (n=1172) using area under the receiver operator characteristic curve analysis. A masked effect was associated with male sex, a positive clinic blood pressure change (difference between consecutive measurements during a single visit), and a diagnosis of hypertension. Increasing age, clinic blood pressure level, and pulse pressure were associated with a white coat effect. The model showed good calibration across data sets (Pearson correlation, 0.48-0.80) and performed well-predicting ambulatory hypertension (area under the receiver operator characteristic curve, 0.75; 95% confidence interval, 0.72-0.79 [systolic]; 0.87; 0.85-0.89 [diastolic]). Used as a triaging tool for ambulatory monitoring, the model improved classification of a patient's blood pressure status compared with other guideline recommended approaches (93% [92% to 95%] classified correctly; United States, 73% [70% to 75%]; Canada, 74% [71% to 77%]; United Kingdom, 78% [76% to 81%]). This study demonstrates that patient characteristics from a single clinic visit can accurately predict a patient's ambulatory blood pressure. Usage of this prediction tool for triaging of ambulatory monitoring could result in more accurate diagnosis of hypertension and hence more appropriate treatment.

  7. Monoclonal antibody-glial-derived neurotrophic factor fusion protein penetrates the blood-brain barrier in the mouse.

    Science.gov (United States)

    Zhou, Qing-Hui; Boado, Ruben J; Lu, Jeff Zhiqiang; Hui, Eric Ka-Wai; Pardridge, William M

    2010-04-01

    Glial-derived neurotrophic factor (GDNF) is a potent neuroprotective agent for multiple brain disorders, including Parkinson's disease. However, GDNF drug development is difficult because GDNF does not cross the blood-brain barrier (BBB). To enable future drug development of GDNF in mouse models, the neurotrophin was re-engineered as an IgG fusion protein to enable penetration through the BBB after intravenous administration. The 134-amino acid GDNF was fused to the heavy chain of a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR) designated the cTfRMAb. This antibody undergoes receptor-mediated transport across the BBB and acts as a molecular Trojan horse to ferry the GDNF into mouse brain. The cTfRMAb-GDNF fusion protein was expressed by stably transfected Chinese hamster ovary cells, affinity-purified, and the biochemical identity was confirmed by mouse IgG and GDNF Western blotting. The cTfRMAb-GDNF fusion protein was bifunctional and bound with high affinity to both the GDNF receptor alpha1, ED(50) = 1.7 +/- 0.2 nM, and the mouse TfR, ED(50) = 3.2 +/- 0.3 nM. The cTfRMAb-GDNF fusion protein was rapidly taken up by brain, and the brain uptake was 3.1 +/- 0.2% injected dose/g brain at 60 min after intravenous injection of a 1-mg/kg dose of the fusion protein. Brain capillary depletion analysis showed the majority of the fusion protein was transcytosed across the BBB with penetration into brain parenchyma. The brain uptake results indicate it is possible to achieve therapeutic elevations of GDNF in mouse brain with intravenous administration of the cTfRMAb-GDNF fusion protein.

  8. [Recent circumstances in the supply and demand of various blood products in Japan, and appropriate use of blood components or plasma protein derivatives].

    Science.gov (United States)

    Tohyama, H

    1986-10-01

    In Japan, as in the United States and several other advanced countries, the use of fresh frozen plasma (FFP) and albumin has increased dramatically over the past 10 years. Especially in Japan the increase has been at least tenfold, and half of this usage has been for surgery. Most reviews of albumin usage acknowledge that there is a high ratio of wastage, or use in clinical circumstances without a firm scientific basis. Recently Japan has imported an enormous volume of various plasma fraction products such as albumin, Factor VIII etc., or plasma as raw material from foreign countries, especially the United States. As a result, Japan has come to monopolized a quarter of the albumin manufactured in the world, and has therefore received much internal and external criticism from or ethical standpoint. As countermeasures against shortage of these blood products, it will be necessary for doctors to use these blood products more sparingly and to increase the yield of volunteer donor's blood, especially plasma. More red blood cell concentrate should be utilized for hemorrhage in routine surgical operations. Because whole blood transfusion is rarely used except in cases of massive bleeding that cannot be stopped immediately, exchange transfusion has been performed in the United States and European countries recently. Transfusion of FFP is appropriately used only for replacement of coagulation factor deficiencies, massive transfusion etc. in the United States. It should be particularly noted that these carry the risk of transmission of diseases such as hepatitis and possibly AIDS. Albumin is an effective oncotic agent in the treatment of acute shock and in the maintenance of intravascular volume and cardiac output. However, albumin and FFP have no demonstrable effect in the general supportive management of chronic hypoproteinemia and undernutrition.

  9. Effects of Syzygium aromaticum-derived triterpenes on postprandial blood glucose in streptozotocin-induced diabetic rats following carbohydrate challenge.

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    Andile Khathi

    Full Text Available PURPOSE: Recent reports suggest that the hypoglycaemic effects of the triterpenes involve inhibition of glucose transport in the small intestine. Therefore, the effects of Syzygium spp-derived triterpenes oleanolic acid (OA and maslinic acid (MA were evaluated on carbohydrate hydrolyzing enzymes in STZ-induced diabetic rats and consequences on postprandial hyperglycaemia after carbohydrate loading. METHODS: We determined using Western blot analysis the expressions of α-amylase and α-glucosidase and glucose transporters SGLT1 and GLUT2 in the small intestine intestines isolated from diabetic rats treated with OA/MA for 5 weeks. In vitro assays were used to assess the inhibitory activities of OA and MA against α-amylase, α-glucosidase and sucrase. RESULTS: OA and MA ameliorated postprandial hyperglycemia in carbohydrate loaded diabetic rats as indicated by the significantly small glucose area under the curve (AUC in treated diabetic animals compared with that in untreated diabetic rats. Western blotting showed that OA and MA treatment not only down-regulated the increase of SGLT1 and GLUT2 expressions in the small intestine of STZ-induced diabetic rats, but also inhibited small intestine α-amylase, sucrase and α-glucosidase activity. IC50 values of OA against α-amylase (3.60 ± 0.18 mmol/L, α-glucosidase (12.40 ± 0.11 mmol/L and sucrase (11.50 ± 0.13 mmol/L did not significantly differ from those of OA and acarbose. CONCLUSIONS: The results of suggest that OA and MA may be used as potential supplements for treating postprandial hyperglycemia. NOVELTY OF THE WORK: The present observations indicate that besides improving glucose homeostasis in diabetes, OA and MA suppress postprandial hyperglycaemia mediated in part via inhibition of carbohydrate hydrolysis and reduction of glucose transporters in the gastrointestinal tract. Inhibition of α-glucosidase and α-amylase can significantly decrease the postprandial hyperglycaemia after a mixed

  10. Human Brain Microvascular Endothelial Cells Derived from the BC1 iPS Cell Line Exhibit a Blood-Brain Barrier Phenotype

    OpenAIRE

    Katt, Moriah E.; Xu, Zinnia S.; Gerecht, Sharon; Searson, Peter C.

    2016-01-01

    The endothelial cells that form capillaries in the brain are highly specialized, with tight junctions that minimize paracellular transport and an array of broad-spectrum efflux pumps that make drug delivery to the brain extremely challenging. One of the major limitations in blood-brain barrier research and the development of drugs to treat central nervous system diseases is the lack of appropriate cell lines. Recent reports indicate that the derivation of human brain microvascular endothelial...

  11. After injection into the striatum, in vitro-differentiated microglia- and bone marrow-derived dendritic cells can leave the central nervous system via the blood stream.

    Science.gov (United States)

    Hochmeister, Sonja; Zeitelhofer, Manuel; Bauer, Jan; Nicolussi, Eva-Maria; Fischer, Marie-Therese; Heinke, Bernhard; Selzer, Edgar; Lassmann, Hans; Bradl, Monika

    2008-12-01

    The prototypic migratory trail of tissue-resident dendritic cells (DCs) is via lymphatic drainage. Since the central nervous system (CNS) lacks classical lymphatic vessels, and antigens and cells injected into both the CNS and cerebrospinal fluid have been found in deep cervical lymph nodes, it was thought that CNS-derived DCs exclusively used the cerebrospinal fluid pathway to exit from tissues. It has become evident, however, that DCs found in peripheral organs can also leave tissues via the blood stream. To study whether DCs derived from microglia and bone marrow can also use this route of emigration from the CNS, we performed a series of experiments in which we injected genetically labeled DCs into the striata of rats. We show here that these cells migrated from the injection site to the perivascular space, integrated into the endothelial lining of the CNS vasculature, and were then present in the lumen of CNS blood vessels days after the injection. Moreover, we also found these cells in both mesenteric lymph nodes and spleens. Hence, microglia- and bone marrow-derived DCs can leave the CNS via the blood stream.

  12. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice.

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    Ravid Shechter

    2009-07-01

    Full Text Available BACKGROUND: Although macrophages (MPhi are known as essential players in wound healing, their contribution to recovery from spinal cord injury (SCI is a subject of debate. The difficulties in distinguishing between different MPhi subpopulations at the lesion site have further contributed to the controversy and led to the common view of MPhi as functionally homogenous. Given the massive accumulation in the injured spinal cord of activated resident microglia, which are the native immune occupants of the central nervous system (CNS, the recruitment of additional infiltrating monocytes from the peripheral blood seems puzzling. A key question that remains is whether the infiltrating monocyte-derived MPhi contribute to repair, or represent an unavoidable detrimental response. The hypothesis of the current study is that a specific population of infiltrating monocyte-derived MPhi is functionally distinct from the inflammatory resident microglia and is essential for recovery from SCI. METHODS AND FINDINGS: We inflicted SCI in adult mice, and tested the effect of infiltrating monocyte-derived MPhi on the recovery process. Adoptive transfer experiments and bone marrow chimeras were used to functionally distinguish between the resident microglia and the infiltrating monocyte-derived MPhi. We followed the infiltration of the monocyte-derived MPhi to the injured site and characterized their spatial distribution and phenotype. Increasing the naïve monocyte pool by either adoptive transfer or CNS-specific vaccination resulted in a higher number of spontaneously recruited cells and improved recovery. Selective ablation of infiltrating monocyte-derived MPhi following SCI while sparing the resident microglia, using either antibody-mediated depletion or conditional ablation by diphtheria toxin, impaired recovery. Reconstitution of the peripheral blood with monocytes resistant to ablation restored the lost motor functions. Importantly, the infiltrating monocyte-derived

  13. Correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in maliagnant solitary pulmonary nodules and tumor size

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    Chenshi ZHANG

    2008-02-01

    Full Text Available Background and Objective The solitary pulmonary nodules (SPNs is one of the most common findings on chest radiographs. It becomes possible to provide more accurately quantitative information about blood flow patterns of solitary pulmonary nodules (SPNs with multi-slice spiral computed tomography (MSCT. The aim of this study is to evaluate the correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in maliagnant solitary pulmonary nodules and tumor size. Methods 68 patients with maliagnant solitary pulmonary nodules (SPNs (diameter <=4 cmunderwent multi-location dynamic contrast material-enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4mL/s by an autoinjector, 4*5mm or 4*2.5mm scanning mode with stable table were performed. serial CT. Precontrast and postcontrast attenuation on every scan was recorded. Perfusion (PSPN, peak height (PHSPNratio of peak height of the SPN to that of the aorta (SPN-to-A ratioand mean transit time(MTT were calculated. The correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in maliagnant solitary pulmonary nodules and tumor size were assessed by means of linear regression analysis. Results No significant correlations were found between the tumor size and each of the peak height (PHSPN ratio of peak height of the SPN to that of the aorta (SPN-to-A ratio perfusion(PSPNand mean transit time (r=0.18, P=0.14; r=0.20,P=0.09; r=0.01, P=0.95; r=0.01, P=0.93. Conclusion No significant correlation is found between the tumor size and each of the quantifiable parameters of blood flow pattern derived with dynamic CT in maliagnant solitary pulmonary nodules.

  14. Derivation of a measure of systolic blood pressure mutability: a novel information theory-based metric from ambulatory blood pressure tests.

    Science.gov (United States)

    Contreras, Danitza J; Vogel, Eugenio E; Saravia, Gonzalo; Stockins, Benjamin

    2016-03-01

    We provide ambulatory blood pressure (BP) exams with tools based on information theory to quantify fluctuations thus increasing the capture of dynamic test components. Data from 515 ambulatory 24-hour BP exams were considered. Average age was 54 years, 54% were women, and 53% were under BP treatment. The average systolic pressure (SP) was 127 ± 8 mm Hg. A data compressor (wlzip) designed to recognize meaningful information is invoked to measure mutability which is a form of dynamical variability. For patients with the same average SP, different mutability values are obtained which reflects the differences in dynamical variability. In unadjusted linear regression models, mutability had low association with the mean systolic BP (R(2) = 0.056; P information toward diagnosis.

  15. Generalized Liver- and Blood-Derived CD8+ T-Cell Impairment in Response to Cytokines in Chronic Hepatitis C Virus Infection.

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    Stephanie C Burke Schinkel

    Full Text Available Generalized CD8+ T-cell impairment in chronic hepatitis C virus (HCV infection and the contribution of liver-infiltrating CD8+ T-cells to the immunopathogenesis of this infection remain poorly understood. It is hypothesized that this impairment is partially due to reduced CD8+ T-cell activity in response to cytokines such as IL-7, particularly within the liver. To investigate this, the phenotype and cytokine responsiveness of blood- and liver-derived CD8+ T-cells from healthy controls and individuals with HCV infection were compared. In blood, IL-7 receptor α (CD127 expression on bulk CD8+ T-cells in HCV infection was no different than controls yet was lower on central memory T-cells, and there were fewer naïve cells. IL-7-induced signalling through phosphorylated STAT5 was lower in HCV infection than in controls, and differed between CD8+ T-cell subsets. Production of Bcl-2 following IL-7 stimulation was also lower in HCV infection and inversely related to the degree of liver fibrosis. In liver-derived CD8+ T-cells, STAT5 activation could not be increased with cytokine stimulation and basal Bcl-2 levels of liver-derived CD8+ T-cells were lower than blood-derived counterparts in HCV infection. Therefore, generalized CD8+ T-cell impairment in HCV infection is characterized, in part, by impaired IL-7-mediated signalling and survival, independent of CD127 expression. This impairment is more pronounced in the liver and may be associated with an increased potential for apoptosis. This generalized CD8+ T-cell impairment represents an important immune dysfunction in chronic HCV infection that may alter patient health.

  16. Peripheral blood derived induced pluripotent stem cells (iPSCs from a female with familial hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Samantha Barratt Ross

    2017-04-01

    Full Text Available Induced pluripotent stem cells (iPSCs were generated from peripheral blood mononuclear cells (PBMCs obtained from a 62-year-old female with familial hypertrophic cardiomyopathy (HCM. PBMCs were reprogrammed to a pluripotent state following transfection with non-integrative episomal vectors carrying reprogramming factors OCT4, SOX2, LIN28, KLF4 and L-MYC. iPSCs were shown to express pluripotency markers, possess trilineage differentiation potential, carry rare variants identified in DNA isolated directly from the patient's whole blood, have a normal karyotype and no longer carry episomal vectors for reprogramming. This line is a useful resource for identifying unknown genetic causes of HCM.

  17. Feed-derived volatile basic nitrogen increases reactive oxygen species production of blood leukocytes in lactating dairy cows.

    Science.gov (United States)

    Tsunoda, Ei; Gross, Josef J; Kawashima, Chiho; Bruckmaier, Rupert M; Kida, Katsuya; Miyamoto, Akio

    2017-01-01

    The present study investigated over 9 months the changes of fermentative quality of total mixed rations (TMR) containing grass silage (GS) as a major component, associated with changes in the volatile basic nitrogen (VBN) levels in an experimental dairy farm. Effects of VBN levels in TMR on metabolic parameters, reactive oxygen species (ROS) production by blood polymorphonuclear leukocytes (PMNs) and conception rates for dairy cows were analyzed. According to VBN levels in TMR during survey periods, three distinct phases were identified; phase A with low VBN; phase B with high VBN; and phase C with mid-VBN. Metabolic parameters in blood were all within normal range. However, during phases B and C, nitrogen metabolic indices such as blood urea nitrogen and milk urea nitrogen showed higher levels compared to those in phase A, and a simultaneous increase in ROS production by blood PMNs and the load on hepatic function in metabolic parameters was observed in the cows with a lower conception rate. This suggests that feeding TMR with elevated VBN levels due to poor fermented GS results in stimulation of ROS production by PMNs by ammonia, and negatively affects metabolism and reproductive performance in lactating dairy cow.

  18. Lyophilized bovine hemoglobin as a possible reference material for the determination of hemoglobin derivatives in human blood

    NARCIS (Netherlands)

    Maas, BHA; Buursma, A; Ernst, RAJ; Maas, AHJ; Zijlstra, WG

    1998-01-01

    We investigated the suitability of a lyophilized bovine hemoglobin (LBH) preparation containing various fractions of oxyhemoglobin (O(2)Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) for quality assessment in multicomponent analysis (MCA) of hemoglobin derivatives. It was demonstrated that

  19. Conformational analysis of thioglycoside derivatives of histo-blood group ABH antigens using an ab initio-derived reparameterization of MM4: implications for design of non-hydrolysable mimetics

    Science.gov (United States)

    Strino, Francesco; Lii, Jenn-Huei; Gabius, Hans-Joachim; Nyholm, Per-Georg

    2009-12-01

    Histo-blood group ABH antigens serve as recognition sites for infectious microorganisms and tissue lectins in intercellular communication, e.g. in tumor progression. Thus, they are of interest as a starting point for drug design. In this respect, potent non-hydrolysable derivatives such as thioglycosides are of special interest. As prerequisite to enable estimations of ligand properties relative to their natural counterparts, conformational properties of the thioglycosidic derivatives of ABH trisaccharides and their disaccharide units were calculated using systematic and filtered systematic searches with the MM4 force field. Parameters for the glycosidic torsions of thioglycosides were independently derived from ab initio calculations. The resulting energy deviations required a reparameterization of MM4 to a new parameter set called MM4R. The data sets obtained using MM4R reveal that the thioglycosides have somewhat increased levels of flexibility about the major low-energy conformations shared with the corresponding O-glycosides. In the trisaccharides, the thiosubstitution of the Gal[NAc]α1-3Gal linkage leads to a preference for a conformation which is the secondary minimum of the natural counterparts. This conformation also generates contacts between the N-acetyl group and the fucose moiety in the blood group A derivative. Calculations further indicate that thiosubstitution of only the Fucα1-2Gal linkage does not affect the conformational preferences compared to the natural trisaccharide. Thiosubstitution of both linkages in the trisaccharide results in increased flexibility but the favored conformation of the natural trisaccharides is preferred. The study suggests that thioglycoside derivatives of ABH antigens could have pharmaceutical interest as ligands of lectins and other carbohydrate-binding proteins.

  20. Human XCR1+ Dendritic Cells Derived In Vitro from CD34+ Progenitors Closely Resemble Blood Dendritic Cells, Including Their Adjuvant Responsiveness, Contrary to Monocyte-Derived Dendritic Cells

    OpenAIRE

    S. Balan; Ollion, V.; Colletti, N.; Chelbi, R.; Montanana-Sanchis, F.; LIU, H.; Vu Manh, T.-P.; Sanchez, C.; Savoret, J.; Perrot, I.; Doffin, A.-C.; Fossum, E.; Bechlian, D.; Chabannon, C.; Bogen, B

    2014-01-01

    Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1+ DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1+ human DC. Assessment of the immunoactivation potential of XCR1+ human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1+ and XCR1− human DC in CD3...

  1. Effect of glatiramer acetate on peripheral blood brain-derived neurotrophic factor and phosphorylated TrkB levels in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Vacaras, Vitalie; Major, Zsigmond Z; Muresanu, Dafin F; Krausz, Tibor L; Marginean, Ioan; Buzoianu, Dana A

    2014-01-01

    Glatiramer acetate (GA) is one of the most widely used disease-modifying drugs for the treatment of relapsing-remitting multiple sclerosis; is assumed to have inductor effects on neurotrophic factor expression. One of these neurotrophic factor systems is the brain-derived neurotrophic factor (BDNF)/receptor tyrosine kinase B (TrkB) pathway. Peripheral blood is thought to contain soluble BDNF, and some blood cells express TrkB. We attempted to determine whether GA treatment leads to changes in plasma BDNF levels and TrkB activation. Such a phenomenon are relapsing-remitting multiple sclerosis patients is significantly reduced; GA treatment is not influencing peripheral BDNF levels, after one year of sustained therapy, not from the point of view of total free BDNF nor the phosphorylated TrkB.

  2. Adjustment of Cell-Type Composition Minimizes Systematic Bias in Blood DNA Methylation Profiles Derived by DNA Collection Protocols.

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    Yuh Shiwa

    Full Text Available Differences in DNA collection protocols may be a potential confounder in epigenome-wide association studies (EWAS using a large number of blood specimens from multiple biobanks and/or cohorts. Here we show that pre-analytical procedures involved in DNA collection can induce systematic bias in the DNA methylation profiles of blood cells that can be adjusted by cell-type composition variables. In Experiment 1, whole blood from 16 volunteers was collected to examine the effect of a 24 h storage period at 4°C on DNA methylation profiles as measured using the Infinium HumanMethylation450 BeadChip array. Our statistical analysis showed that the P-value distribution of more than 450,000 CpG sites was similar to the theoretical distribution (in quantile-quantile plot, λ = 1.03 when comparing two control replicates, which was remarkably deviated from the theoretical distribution (λ = 1.50 when comparing control and storage conditions. We then considered cell-type composition as a possible cause of the observed bias in DNA methylation profiles and found that the bias associated with the cold storage condition was largely decreased (λ adjusted = 1.14 by taking into account a cell-type composition variable. As such, we compared four respective sample collection protocols used in large-scale Japanese biobanks or cohorts as well as two control replicates. Systematic biases in DNA methylation profiles were observed between control and three of four protocols without adjustment of cell-type composition (λ = 1.12-1.45 and no remarkable biases were seen after adjusting for cell-type composition in all four protocols (λ adjusted = 1.00-1.17. These results revealed important implications for comparing DNA methylation profiles between blood specimens from different sources and may lead to discovery of disease-associated DNA methylation markers and the development of DNA methylation profile-based predictive risk models.

  3. New type of Sendai virus vector provides transgene-free iPS cells derived from chimpanzee blood.

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    Yasumitsu Fujie

    Full Text Available Induced pluripotent stem cells (iPSCs are potentially valuable cell sources for disease models and future therapeutic applications; however, inefficient generation and the presence of integrated transgenes remain as problems limiting their current use. Here, we developed a new Sendai virus vector, TS12KOS, which has improved efficiency, does not integrate into the cellular DNA, and can be easily eliminated. TS12KOS carries KLF4, OCT3/4, and SOX2 in a single vector and can easily generate iPSCs from human blood cells. Using TS12KOS, we established iPSC lines from chimpanzee blood, and used DNA array analysis to show that the global gene-expression pattern of chimpanzee iPSCs is similar to those of human embryonic stem cell and iPSC lines. These results demonstrated that our new vector is useful for generating iPSCs from the blood cells of both human and chimpanzee. In addition, the chimpanzee iPSCs are expected to facilitate unique studies into human physiology and disease.

  4. Human Brain Microvascular Endothelial Cells Derived from the BC1 iPS Cell Line Exhibit a Blood-Brain Barrier Phenotype.

    Science.gov (United States)

    Katt, Moriah E; Xu, Zinnia S; Gerecht, Sharon; Searson, Peter C

    2016-01-01

    The endothelial cells that form capillaries in the brain are highly specialized, with tight junctions that minimize paracellular transport and an array of broad-spectrum efflux pumps that make drug delivery to the brain extremely challenging. One of the major limitations in blood-brain barrier research and the development of drugs to treat central nervous system diseases is the lack of appropriate cell lines. Recent reports indicate that the derivation of human brain microvascular endothelial cells (hBMECs) from human induced pluripotent stem cells (iPSCs) may provide a solution to this problem. Here we demonstrate the derivation of hBMECs extended to two new human iPSC lines: BC1 and GFP-labeled BC1. These hBMECs highly express adherens and tight junction proteins VE-cadherin, ZO-1, occludin, and claudin-5. The addition of retinoic acid upregulates VE-cadherin expression, and results in a significant increase in transendothelial electrical resistance to physiological values. The permeabilities of tacrine, rhodamine 123, and Lucifer yellow are similar to values obtained for MDCK cells. The efflux ratio for rhodamine 123 across hBMECs is in the range 2-4 indicating polarization of efflux transporters. Using the rod assay to assess cell organization in small vessels and capillaries, we show that hBMECs resist elongation with decreasing diameter but show progressive axial alignment. The derivation of hBMECs with a blood-brain barrier phenotype from the BC1 cell line highlights that the protocol is robust. The expression of GFP in hBMECs derived from the BC1-GFP cell line provides an important new resource for BBB research.

  5. Comparison of buccal and blood-derived canine DNA, either native or whole genome amplified, for array-based genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Lawley Cynthia

    2011-06-01

    Full Text Available Abstract Background The availability of array-based genotyping platforms for single nucleotide polymorphisms (SNPs for the canine genome has expanded the opportunities to undertake genome-wide association (GWA studies to identify the genetic basis for Mendelian and complex traits. Whole blood as the source of high quality DNA is undisputed but often proves impractical for collection of the large numbers of samples necessary to discover the loci underlying complex traits. Further, many countries prohibit the collection of blood from dogs unless medically necessary thereby restricting access to critical control samples from healthy dogs. Alternate sources of DNA, typically from buccal cytobrush extractions, while convenient, have been suggested to have low yield and perform poorly in GWA. Yet buccal cytobrushes provide a cost-effective means of collecting DNA, are readily accepted by dog owners, and represent a large resource base in many canine genetics laboratories. To increase the DNA quantities, whole genome amplification (WGA can be performed. Thus, the present study assessed the utility of buccal-derived DNA as well as whole genome amplification in comparison to blood samples for use on the most recent iteration of the canine HD SNP array (Illumina. Findings In both buccal and blood samples, whether whole genome amplified or not, 97% of the samples had SNP call rates in excess of 80% indicating that the vast majority of the SNPs would be suitable to perform association studies regardless of the DNA source. Similarly, there were no significant differences in marker intensity measurements between buccal and blood samples for copy number variations (CNV analysis. Conclusions All DNA samples assayed, buccal or blood, native or whole genome amplified, are appropriate for use in array-based genome-wide association studies. The concordance between subsets of dogs for which both buccal and blood samples, or those samples whole genome amplified, was

  6. Blood Types

    Science.gov (United States)

    ... maternity. Learn About Blood Blood Facts and Statistics Blood Components Whole Blood and Red Blood Cells Platelets Plasma ... About Blood Blood Facts and Statistics Blood Types Blood Components What Happens to Donated Blood Blood and Diversity ...

  7. Human umbilical cord blood-derived mesenchymal stem cells do not differentiate into neural cell types or integrate into the retina after intravitreal grafting in neonatal rats.

    Science.gov (United States)

    Hill, Andrew J; Zwart, Isabel; Tam, Henry H; Chan, Jane; Navarrete, Cristina; Jen, Ling-Sun; Navarrete, Roberto

    2009-04-01

    This study investigated the ability of mesenchymal stem cells (MSCs) derived from full-term human umbilical cord blood to survive, integrate and differentiate after intravitreal grafting to the degenerating neonatal rat retina following intracranial optic tract lesion. MSCs survived for 1 week in the absence of immunosuppression. When host animals were treated with cyclosporin A and dexamethasone to suppress inflammatory and immune responses, donor cells survived for at least 3 weeks, and were able to spread and cover the entire vitreal surface of the host retina. However, MSCs did not significantly integrate into or migrate through the retina. They also maintained their human antigenicity, and no indication of neural differentiation was observed in retinas where retinal ganglion cells either underwent severe degeneration or were lost. These results have provided the first in vivo evidence that MSCs derived from human umbilical cord blood can survive for a significant period of time when the host rat response is suppressed even for a short period. These results, together with the observation of a lack of neuronal differentiation and integration of MSCs after intravitreal grafting, has raised an important question as to the potential use of MSCs for neural repair through the replacement of lost neurons in the mammalian retina and central nervous system.

  8. Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells.

    Science.gov (United States)

    Regan, Andrew D; Cohen, Rebecca D; Whittaker, Gary R

    2009-02-05

    Feline infectious peritonitis (FIP) is an invariably fatal disease of cats caused by systemic infection with a feline coronavirus (FCoV) termed feline infectious peritonitis virus (FIPV). The lethal pathology associated with FIP (granulomatous inflammation and T-cell lymphopenia) is thought to be mediated by aberrant modulation of the immune system due to infection of cells such as monocytes and macrophages. Overproduction of pro-inflammatory cytokines occurs in cats with FIP, and has been suggested to play a significant role in the disease process. However, the mechanism underlying this process remains unknown. Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation and pro-inflammatory cytokine production was inhibited by the pyridinyl imidazole inhibitors SB 203580 and SC 409 in a dose-dependent manner. FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors.

  9. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation.

    Science.gov (United States)

    Pluznick, Jennifer L; Protzko, Ryan J; Gevorgyan, Haykanush; Peterlin, Zita; Sipos, Arnold; Han, Jinah; Brunet, Isabelle; Wan, La-Xiang; Rey, Federico; Wang, Tong; Firestein, Stuart J; Yanagisawa, Masashi; Gordon, Jeffrey I; Eichmann, Anne; Peti-Peterdi, Janos; Caplan, Michael J

    2013-03-12

    Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.

  10. Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Tie Chen; Xinzu Chen; Fang Wang; Fan Zeng; Hong Xu; Jiankun Hu; Xianming Mo; Kun Yang; Jianhua Yu; Wentong Meng; Dandan Yuan; Feng Bi; Fang Liu; Jie Liu; Bing Dai

    2012-01-01

    Gastric cancer is the fourth most common cancer worldwide,with a high rate of death and low 5-year survival rate.To date,there is a lack of efficient therapeutic protocols for gastric cancer.Recent studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation,invasion,metastasis,and resistance to anticancer therapies.Thus,therapies that target gastric CSCs are attractive.However,CSCs in human gastric adenocarcinoma (GAC)have not been described.Here,we identify CSCs in tumor tissues and peripheral blood from GAC patients.CSCs of human GAC (GCSCs) that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers,generated tumors that highly resemble the original human tumors when injected into immunodeficient mice,differentiated into gastric epithelial cells in vitro,and self-renewed in vivo and in vitro.Our findings suggest that effective therapeutic protocols must target GCSCs.The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor metastasis,and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.

  11. Pathogenic prion protein fragment (PrP106–126) promotes human immunodeficiency virus type-1 infection in peripheral blood monocyte-derived macrophages

    Science.gov (United States)

    Bacot, Silvia M.; Feldman, Gerald M.; Yamada, Kenneth M.; Dhawan, Subhash

    2017-01-01

    Transfusion of blood and blood products contaminated with the pathogenic form of prion protein Prpsc, thought to be the causative agent of variant a Creutzfeldt–Jakob disease (vCJD), may result in serious consequences in recipients with a compromised immune system, for example, as seen in HIV-1 infection. In the present study, we demonstrate that treatment of peripheral blood monocyte-derived macrophages (MDM) with PrP106–126, a synthetic domain of PrPsc that has intrinsic functional activities related to the full-length protein, markedly increased their susceptibility to HIV-1 infection, induced cytokine secretion, and enhanced their migratory behavior in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence of PrP106–126 showed large cell clusters indicative of cellular activation. Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin-dependent kinase inhibitor olomoucine attenuated PrP106–126-induced altered MDM functions. These findings delineate a previously undefined functional role of PrP106–126-mediated host cell response in promoting HIV-1 pathogenesis. PMID:25589240

  12. Unresolved clinical aspects and safety hazards of blood derived- EV/MV in stored blood components: From personal memory lanes to newer perspectives on the roles of EV/MV in various biological phenomena.

    Science.gov (United States)

    Seghatchian, Jerard; Amiral, Jean

    2016-08-01

    Blood cells generate heterogeneous populations of vesicles that are delivered, as small-specialized packages of highly active cell fragments in blood circulation, having almost similar functional activities, as the mother cells. These so called extracellular vesicles are the essential part of an energy-dependent natural apoptotic process; hence their beneficial and harmful biological functions cannot be ignored. Evidence is accumulating, that cellular derived vesicles, originate from all viable cells including: megakaryocytes, platelets, red blood cells, white blood cells and endothelial cells, the highest in proportions from platelets. Shedding can also be triggered by pathological activation of inflammatory processes and activation of coagulation or complement pathways, or even by shear stress in the circulation. Structurally, so called MV/EV appear to be, sometimes inside-out and sometimes outside-in cell fragments having a bilayered phospholipid structure exposing coagulant-active phosphatidylserine, expressing various membrane receptors, and they serve as cell-to-cell shuttles for bioactive molecules such as lipids, growth factors, microRNAs, and mitochondria. Ex vivo processing of blood into its components, embodying centrifugation, processing by various apheresis procedures, leukoreduction, pathogen reduction, and finally storage in different media and different types of blood bags, also have major impacts on the generation and retention of MV content. These artificially generated small, but highly liable packages, together with the original pool of MVs collected from the donor, do exhibit differing biological activities, and are not inert elements and should be considered as a parameter of blood safety in haemovigilance programmes. Harmonization and consensus in sampling protocols, sample handling, processing, and assessment methods, in particular converting to full automation, are needed to achieve consensual interpretations. This review focuses on some of

  13. Modulation of Chemokine Gene Expression in CD133 Cord Blood-Derived Human Mast Cells by Cyclosporin A and Dexamethasone

    DEFF Research Database (Denmark)

    Holm, Mette; Kvistgaard, Helene; Dahl, Christine;

    2006-01-01

    We have recently developed a protocol for generating huge numbers of mature and functional mast cells from in vitro differentiated umbilical cord blood cells. Using CD133 as a positive selection marker to isolate haematopoietic progenitors we routinely expand the number of recovered cells at least...... 150-fold, which vastly exceeds the yields of conventional protocols using CD34(+) cells as a source of progenitors. Taking advantage of the large quantities of in vitro differentiated mast cells, here we assess at the levels of transcription and translation the kinetics of chemokine gene induction...... following receptor mediated mast cell activation or following pharmacological activation of specific signal transduction cascades that become activated upon classical FcepsilonRI receptor crosslinking. We demonstrate that chemokine genes encoding IL-8, MCP-1, MIP-1alpha, and MIP-1beta are induced...

  14. Differences in AMY1 Gene Copy Numbers Derived from Blood, Buccal Cells and Saliva Using Quantitative and Droplet Digital PCR Methods: Flagging the Pitfall

    Science.gov (United States)

    Ong, Siong Gim; Chan, Yiong Huak; Heng, Chew Kiat

    2017-01-01

    Introduction The human salivary (AMY1) gene, encoding salivary α-amylase, has variable copy number variants (CNVs) in the human genome. We aimed to determine if real-time quantitative polymerase chain reaction (qPCR) and the more recently available Droplet Digital PCR (ddPCR) can provide a precise quantification of the AMY1 gene copy number in blood, buccal cells and saliva samples derived from the same individual. Methods Seven participants were recruited and DNA was extracted from the blood, buccal cells and saliva samples provided by each participant. Taqman assay real-time qPCR and ddPCR were conducted to quantify AMY1 gene copy numbers. Statistical analysis was carried out to determine the difference in AMY1 gene copy number between the different biological specimens and different assay methods. Results We found significant within-individual difference (p<0.01) in AMY1 gene copy number between different biological samples as determined by qPCR. However, there was no significant within-individual difference in AMY1 gene copy number between different biological samples as determined by ddPCR. We also found that AMY1 gene copy number of blood samples were comparable between qPCR and ddPCR, while there is a significant difference (p<0.01) between AMY1 gene copy numbers measured by qPCR and ddPCR for both buccal swab and saliva samples. Conclusions Despite buccal cells and saliva samples being possible sources of DNA, it is pertinent that ddPCR or a single biological sample, preferably blood sample, be used for determining highly polymorphic gene copy numbers like AMY1, due to the large within-individual variability between different biological samples if real time qPCR is employed. PMID:28125683

  15. Buccal cell FISH and blood PCR-Y detect high rates of X chromosomal mosaicism and Y chromosomal derivatives in patients with Turner syndrome.

    Science.gov (United States)

    Freriks, Kim; Timmers, Henri J L M; Netea-Maier, Romana T; Beerendonk, Catharina C M; Otten, Barto J; van Alfen-van der Velden, Janiëlle A E M; Traas, Maaike A F; Mieloo, Hanneke; van de Zande, Guillaume W H J F L; Hoefsloot, Lies H; Hermus, Ad R M M; Smeets, Dominique F C M

    2013-09-01

    Turner syndrome (TS) is the result of (partial) X chromosome monosomy. In general, the diagnosis is based on karyotyping of 30 blood lymphocytes. This technique, however, does not rule out tissue mosaicism or low grade mosaicism in the blood. Because of the associated risk of gonadoblastoma, mosaicism is especially important in case this involves a Y chromosome. We investigated different approaches to improve the detection of mosaicisms in 162 adult women with TS (mean age 29.9 ± 10.3). Standard karyotyping identified 75 patients (46.3%) with a non-mosaic monosomy 45,X. Of these 75 patients, 63 underwent additional investigations including FISH on buccal cells with X- and Y-specific probes and PCR-Y on blood. FISH analysis of buccal cells revealed a mosaicism in 19 of the 63 patients (30.2%). In five patients the additional cell lines contained a (derivative) Y chromosome. With sensitive real-time PCR we confirmed the presence of this Y chromosome in blood in three of the five cases. Although Y chromosome material was established in ovarian tissue in two patients, no gonadoblastoma was found. Our results confirm the notion that TS patients with 45,X on conventional karyotyping often have tissue specific mosaicisms, some of which include a Y chromosome. Although further investigations are needed to estimate the risk of gonadoblastoma in patients with Y chromosome material in buccal cells, we conclude that FISH or real-time PCR on buccal cells should be considered in TS patients with 45,X on standard karyotyping.

  16. Mature dendritic cells derived from human monocytes within 48 hours: a novel strategy for dendritic cell differentiation from blood precursors.

    Science.gov (United States)

    Dauer, Marc; Obermaier, Bianca; Herten, Jan; Haerle, Carola; Pohl, Katrin; Rothenfusser, Simon; Schnurr, Max; Endres, Stefan; Eigler, Andreas

    2003-04-15

    It is widely believed that generation of mature dendritic cells (DCs) with full T cell stimulatory capacity from human monocytes in vitro requires 5-7 days of differentiation with GM-CSF and IL-4, followed by 2-3 days of activation. Here, we report a new strategy for differentiation and maturation of monocyte-derived DCs within only 48 h of in vitro culture. Monocytes acquire immature DC characteristics by day 2 of culture with GM-CSF and IL-4; they down-regulate CD14, increase dextran uptake, and respond to the inflammatory chemokine macrophage inflammatory protein-1alpha. To accelerate DC development and maturation, monocytes were incubated for 24 h with GM-CSF and IL-4, followed by activation with proinflammatory mediators for another 24 h (FastDC). FastDC expressed mature DC surface markers as well as chemokine receptor 7 and secreted IL-12 (p70) upon CD40 ligation in the presence of IFN-gamma. The increase in intracellular calcium in response to 6Ckine showed that chemokine receptor 7 expression was functional. When FastDC were compared with mature monocyte-derived DCs generated by a standard 7-day protocol, they were equally potent in inducing Ag-specific T cell proliferation and IFN-gamma production as well as in priming autologous naive T cells using tetanus toxoid as a model Ag. These findings indicate that FastDC are as effective as monocyte-derived DCs in stimulating primary, Ag-specific, Th 1-type immune responses. Generation of FastDC not only reduces labor, cost, and time required for in vitro DC development, but may also represent a model more closely resembling DC differentiation from monocytes in vivo.

  17. Effects of dermatan sulfate derivatives on platelet surface P-selectin expression and protein C activity in blood of inflammatory bowel disease patients

    Institute of Scientific and Technical Information of China (English)

    Sheng-Li Ji; Hai-Yan Du; Yan-Qing Chi; Hui-Fei Cui; Ji-Chao Cao; Mei-Yu Geng; Hua-Shi Guan

    2004-01-01

    AIM: To investigate the effect of dermatan sulfate (DS)derivatives on platelet surface P-selectin expression and blood activated protein C (APC) activity in patients with inflammatory bowel disease (IBD), and to clarity the antiinflammatory mechanism of DS derivatives.METHODS: Dermatan sulfate (DS) was sulfated with chlorosulfonic acid to prepare polysulfated dermatan sulfate (PSDS). The major disaccharides of DS and PSDS were determined by 1H nuclear magnetic resonance spectroscopy (1H-NMR) and 13C-NMR. Both DS and PSDS were depolymerized with hydrogen peroxide. The fragments were separated by gel filtration chromatography. The effects of DS derivatives on P-selectin expression were assayed by ELISA method,and blood APC activity was assayed by the synthetic chromogenic substrate method.RESULTS: The major disaccharides of DS and PSDS were IdoA-1→3-GalNAc-4-SO3 and IdoA-2SO3-1→3-GalNAc4, 6-diSO3, respectively. Compared with the adenosine diphosphate stimulated group and IBD control group, DS and its derivatives all had significant inhibitory effects on P-selectin expression (P<0.01), but there was no difference between DS-derived oligosaccharides (DSOSs) and PSDS-derived oligosaccharides (PSDSOSs). The experiments on APC activity showed that DS and its derivatives all enhanced APC activity. The most active DSOS was the one with a relative molecular weight (Mr) of 4 825, which enhanced the APC activity from 106.5±11.5% to 181.8±22.3% (P<0.01). With the decrease of Mr, the activity of DSOSs decreased gradually. The effect of PSDS on APC activity enhancement was more significant than that of DS, and the APC activity was raised to 205.2±22.1% (P<0.01). All the PSDSOSs were more active than DSOSs on the basis of comparable Mr. With the decrease of Mr, the activity of PSDSOSs increased gradually, and the most active PSDSOS was PSDSOS3 with Mr of 2 749, which enhanced the APC activity to 331.2±27.8% (P<0.01), then the activity of PSDSOSs decreased gradually

  18. MicroRNAs as markers for neurally committed CD133+/CD34+ stem cells derived from human umbilical cord blood.

    Science.gov (United States)

    Hafizi, Maryam; Atashi, Amir; Bakhshandeh, Behnaz; Kabiri, Mahboubeh; Nadri, Samad; Hosseini, Reza Haji; Soleimani, Masoud

    2013-04-01

    Neural differentiation of the CD133+/CD34+ subpopulation of human umbilical cord blood stem cells was investigated, and neuro-miR (mir-9 and mir-124) expression was examined. An efficient induction protocol for neural differentiation of hematopoietic stem cells together with the exclusion of retinoic acid in this process was also studied. Transcription of some neural markers such as microtubule-associated protein-2, beta-tubulin III, and neuron-specific enolase was evaluated by real-time PCR, immunocytochemistry, and western blotting. Increased expression of neural indicators in the treated cells confirmed the appropriate neural differentiation, which supported the high efficiency of our defined neuronal induction protocol. Verified high expression of neuro-miRNAs along with neuronal specific proteins not only strengthens the regulatory role of miRNAs in determining stem cell fate but also introduces these miRNAs as novel indicators of neural differentiation. These data highlight the prominent therapeutic potential of hematopoietic stem cells for use in cell therapy of neurodegenerative diseases.

  19. Induction of differentiation by down-regulation of Nanog and Rex-1 in cord blood derived unrestricted somatic stem cells.

    Science.gov (United States)

    Langroudi, Lida; Forouzandeh, Mehdi; Soleimani, Masoud; Atashi, Amir; Golestaneh, Azadeh Fahim

    2013-07-01

    Stem cells with high self-renewal and tissue regeneration potentials are the core components of regenerative medicine. Adult stem cells with many available sources, high repairing ability, and also possessing no ethical issues are popular candidates in the clinical field. In this study we looked upon the effects of two transcription factors Nanog and Rex-1 in self-renewal and differentiation abilities of a subpopulation of cord blood stem cells known as unrestricted somatic stem cells (USSCs). USSCs were expanded and transfected in vitro with siRNAs targeting either Nanog, Rex-1, and in combination. Gene suppressions were achieved at both transcript and proteome level. Differentiations were evaluated by specific Real time PCR and differentiating staining. Nanog knock down revealed a significant increase in osteogenic markers, Osteocalcin and Osteopontin expression as well as a positive Alizarin Red staining, which proposes Osteogenesis. This treatment also became positive for Oil Red staining, implying adipogenic differentiation as well. In contrast, Rex-1 knock down showed an increase in MAP II and Nestin expression, which is a hall mark of neural differentiation. Surprisingly, treatment with both siRNAs did not express any changes in any of the assessed markers. Therefore, our results indicated a bilateral mesenchymal differentiation for Nanog and a neural lineage fate for Rex-1 suppression. Considering that both transcription factors are core activators of self-renewal and also are orchestrating with other factors, our results imply a positive feedback in response to changes in the regulatory network of self-renewal.

  20. A comparison of umbilical cord blood-derived endothelial progenitor and mononuclear cell transplantation for the treatment of acute hindlimb ischemia

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2014-01-01

    Full Text Available Acute lower limb ischemia is a common peripheral artery disease whose treatment presents many difficulties. Stem cell transplantation is considered a novel and promising method of treating this disease. Umbilical cord blood (UCB is rich in stem cells, including hematopoietic stem cells (HSCs, mesenchymal stem cells (MSCs and endothelial progenitor cells (EPCs. However, historically, banked umbilical cord blood has been used mainly to treat blood-related diseases. Therefore, this study compared the efficacy of umbilical cord bloodderived mononuclear cells (UCB-MNCs with EPC transplantation for the treatment of acute hindlimb ischemia (ALI in mouse models. MNCs were isolated from UCB by Ficoll gradient centrifugation, after which the EPCs were sorted based on CD34+ and CD133+ markers and cultured according to a previously published protocol. To induce ALI, mice were immuno-suppressed using busulfan (BU and cyclophosphamide (CY, after which the femoral arteries were burned. Induction of ALI in the immune suppressed mice was confirmed by the grade of tissue damage, pedal frequency in water, tissue edema, changes in histology, total white blood cell count, and white blood cell composition. Model mice were injected with a dose of MNCs or EPCs and un-treated control mice were injected with phosphate buffered saline. The efficiency of treatment was evaluated by comparing the grade of tissue damage between the three groups of mice. Mice aged 6 and ndash;12 months were suitable for ALI, with 100% of mice exhibiting ischemia from grade I 10%, grade III 50%, grade IV 40%. For all ALI mice, a gradual increase in pedal frequency in water, increased tissue edema, necrosis of muscle tissue, and loss of hindlimb function were observed after 20 days. Transplanted MNCs and EPCs significantly improved hindlimb ischemia compared with control treatment. Moreover, EPC transplantation significantly improved hindlimb ischemia compared with MNC transplantation. Following

  1. Blood meal-derived heme decreases ROS levels in the midgut of Aedes aegypti and allows proliferation of intestinal microbiota.

    Directory of Open Access Journals (Sweden)

    Jose Henrique M Oliveira

    2011-03-01

    Full Text Available The presence of bacteria in the midgut of mosquitoes antagonizes infectious agents, such as Dengue and Plasmodium, acting as a negative factor in the vectorial competence of the mosquito. Therefore, knowledge of the molecular mechanisms involved in the control of midgut microbiota could help in the development of new tools to reduce transmission. We hypothesized that toxic reactive oxygen species (ROS generated by epithelial cells control bacterial growth in the midgut of Aedes aegypti, the vector of Yellow fever and Dengue viruses. We show that ROS are continuously present in the midgut of sugar-fed (SF mosquitoes and a blood-meal immediately decreased ROS through a mechanism involving heme-mediated activation of PKC. This event occurred in parallel with an expansion of gut bacteria. Treatment of sugar-fed mosquitoes with increased concentrations of heme led to a dose dependent decrease in ROS levels and a consequent increase in midgut endogenous bacteria. In addition, gene silencing of dual oxidase (Duox reduced ROS levels and also increased gut flora. Using a model of bacterial oral infection in the gut, we show that the absence of ROS resulted in decreased mosquito resistance to infection, increased midgut epithelial damage, transcriptional modulation of immune-related genes and mortality. As heme is a pro-oxidant molecule released in large amounts upon hemoglobin degradation, oxidative killing of bacteria in the gut would represent a burden to the insect, thereby creating an extra oxidative challenge to the mosquito. We propose that a controlled decrease in ROS levels in the midgut of Aedes aegypti is an adaptation to compensate for the ingestion of heme.

  2. Casein-Derived Lactotripeptides Reduce Systolic and Diastolic Blood Pressure in a Meta-Analysis of Randomised Clinical Trials

    Directory of Open Access Journals (Sweden)

    Ágnes A. Fekete

    2015-01-01

    Full Text Available There is an urgent need to treat individuals with high blood pressure (BP with effective dietary strategies. Previous studies suggest a small, but significant decrease in BP after lactotripeptides (LTP ingestion, although the data are inconsistent. The study aim was to perform a comprehensive meta-analysis of data from all relevant randomised controlled trials (RCT. Medline, Cochrane library, EMBASE and Web of Science were searched until May 2014. Eligibility criteria were RCT that examined the effects of LTP on BP in adults, with systolic BP (SBP and diastolic BP (DBP as outcome measures. Thirty RCT met the inclusion criteria, which resulted in 33 sets of data. The pooled treatment effect for SBP was −2.95 mmHg (95% CI: −4.17, −1.73; p < 0.001, and for DBP was −1.51 mmHg (95% CI: −2.21, −0.80; p < 0.001. Sub-group analyses revealed that reduction of BP in Japanese studies was significantly greater, compared with European studies (p = 0.002 for SBP and p < 0.001 for DBP. The 24-h ambulatory BP (AMBP response to LTP supplementation was statistically non-significant (p = 0.101 for SBP and p = 0.166 for DBP. Both publication bias and “small-study effect” were identified, which shifted the treatment effect towards less significant SBP and non-significant DBP reduction after LTP consumption. LTP may be effective in BP reduction, especially in Japanese individuals; however sub-group, meta-regression analyses and statistically significant publication biases suggest inconsistencies.

  3. Structure-activity relationships for metal-labeled blood flow tracers: comparison of keto aldehyde bis(thiosemicarbazonato)copper(II) derivatives.

    Science.gov (United States)

    John, E K; Green, M A

    1990-06-01

    Radiocopper-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II), Cu[PTSM], is under investigation as a radiopharmaceutical for evaluation of regional blood flow in the brain, heart, and kidneys because it affords relatively high levels of radioactivity in these organs upon intravenous injection, followed by prolonged tissue retention of the radiolabel. To probe and differentiate the physicochemical properties that are critical for blood-brain barrier (BBB) penetration and tissue retention in complexes of this type, 17 67Cu-labeled copper(II) bis(thiosemicarbazone) derivatives of Cu[PTSM] have been prepared and characterized, focusing on the bis(thiosemicarbazone), bis(N4-methylthiosemicarbazone), bis(N4-dimethylthiosemicarbazone), and bis(N4-ethylthiosemicarbazone) derivatives of several alkylglyoxals (R(1) = Me, Et, n-Pr, i-Pr, n-Bu, or Me(EtO)CH) and phenylglyoxal. The compounds studied varied in lipophilicity from log P = 0.75 to log P = 3.5 (where P is the octanol/water partition coefficient). In rat biodistribution studies the N4-methylthiosemicarbazone (R(1)TSM) and N4-dimethylthiosemicarbazone (R(1)TSM2) complexes always show comparable cerebral uptake at 1 min postinjection (iv) for any given R(1) group, while the thiosemicarbazone (R(1)TS) complex always penetrates the BBB less efficiently. Comparison of the various Cu[R(1)TS] derivatives shows that their brain uptake does tend to increase with increasing lipophilicity over the range 0.75 less than log P less than 2.4, although it never reaches that of the N4-alkylated derivatives. The Cu[R(1)TS] and Cu[R(1)TSM] complexes are found to exhibit prolonged cerebral retention of activity, consistent with their known susceptibility to reductive decomposition by intracellular sulfhydryl groups, while the more inert Cu[R(1)TSM2] complexes clear from the brain relatively rapidly. Tracer clearance kinetics in the heart and kidney are similar to those observed for the brain with each of the tracers

  4. Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure.

    Science.gov (United States)

    Sun, Bo; Roh, Kyung-Hwan; Lee, Sae-Rom; Lee, Yong-Soon; Kang, Kyung-Sun

    2007-03-23

    Success in islet-transplantation-based therapies for type I diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Embryonic stem cells (ESCs) have been successfully induced into insulin producing islet-like structure in several studies. However, the source of the ESCs has presented ethical and technical concerns. Here, we isolated a population of stem cells from human cord blood (UCB), which expressed embryo stage specific maker, SSEA-4, and the multi-potential stem cell marker, Oct4. Subsequently, we successfully induced them into insulin-producing islet-like structures, which co-express insulin and C-peptide. These findings might have a significant potential to advance human UCB derived stem-cell-based therapeutics for diabetes.

  5. Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Tao; Tsui, Benjamin M. W.; Li, Xin; Vranesic, Melin; Lodge, Martin A.; Gulaldi, Nedim C. M.; Szabo, Zsolt, E-mail: zszabo@jhmi.edu [Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287 (United States)

    2015-11-15

    Purpose: The radioligand {sup 11}C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of {sup 11}C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method in pigs with the goal of translation into human studies. Methods: The experimental animals were injected with [{sup 11}C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function. Results: In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent

  6. Direct Comparison of Wharton's Jelly and Bone Marrow-Derived Mesenchymal Stromal Cells to Enhance Engraftment of Cord Blood CD34+ Transplants

    Science.gov (United States)

    van der Garde, Mark; van Pel, Melissa; Millán Rivero, Jose Eduardo; de Graaf-Dijkstra, Alice; Slot, Manon C.; Kleinveld, Yoshiko; Watt, Suzanne M.; Roelofs, Helene

    2015-01-01

    Cotransplantation of CD34+ hematopoietic stem and progenitor cells (HSPCs) with mesenchymal stromal cells (MSCs) enhances HSPC engraftment. For these applications, MSCs are mostly obtained from bone marrow (BM). However, MSCs can also be isolated from the Wharton's jelly (WJ) of the human umbilical cord. This source, regarded to be a waste product, enables a relatively low-cost MSC acquisition without any burden to the donor. In this study, we evaluated the ability of WJ MSCs to enhance HSPC engraftment. First, we compared cultured human WJ MSCs with human BM-derived MSCs (BM MSCs) for in vitro marker expression, immunomodulatory capacity, and differentiation into three mesenchymal lineages. Although we confirmed that WJ MSCs have a more restricted differentiation capacity, both WJ MSCs and BM MSCs expressed similar levels of surface markers and exhibited similar immune inhibitory capacities. Most importantly, cotransplantation of either WJ MSCs or BM MSCs with CB CD34+ cells into NOD SCID mice showed similar enhanced recovery of human platelets and CD45+ cells in the peripheral blood and a 3-fold higher engraftment in the BM, blood, and spleen 6 weeks after transplantation when compared to transplantation of CD34+ cells alone. Upon coincubation, both MSC sources increased the expression of adhesion molecules on CD34+ cells, although stromal cell-derived factor-1 (SDF-1)-induced migration of CD34+ cells remained unaltered. Interestingly, there was an increase in CFU-GEMM when CB CD34+ cells were cultured on monolayers of WJ MSCs in the presence of exogenous thrombopoietin, and an increase in BFU-E when BM MSCs replaced WJ MSCs in such cultures. Our results suggest that WJ MSC is likely to be a practical alternative for BM MSC to enhance CB CD34+ cell engraftment. PMID:26414086

  7. Xeno-free culture condition for human bone marrow and umbilical cord matrix-derived mesenchymal stem/stromal cells using human umbilical cord blood serum

    Science.gov (United States)

    Esmaeli, Azadeh; Moshrefi, Mojgan; Shamsara, Ali; Eftekhar-vaghefi, Seyed Hasan; Nematollahi-mahani, Seyed Noureddin

    2016-01-01

    Background: Fetal bovine serum (FBS) is widely used in cell culture laboratories, risk of zoonotic infections and allergic side effects create obstacles for its use in clinical trials. Therefore, an alternative supplement with proper inherent growth-promoting activities is demanded. Objective: To find FBS substitute, we tested human umbilical cord blood serum (hUCS) for proliferation of human umbilical cord matrix derived mesenchymal stem cells (hUC-MSCs) and human bone marrow-derived mesenchymal cells (hBM-MSCs). Materials and Methods: Umbilical cord blood of healthy neonates, delivered by Caesarian section, was collected and the serum was separated. hUC-MSCs and hBM-MSCs were isolated and characterized by assessment of cell surface antigens by flow cytometry, alkaline phosphatase activity and osteogenic/adipogenic differentiation potential. The cells were then cultured in Iscove's Modified Dulbecco's Medium (IMDM) by conventional methods in three preparations: 1- with hUCS, 2- with FBS, and 3- without serum supplements. Cell proliferation was measured using WST-1 assay, and cell viability was assessed by trypan blue staining. Results: The cells cultured in hUCS and FBS exhibited similar morphology and mesenchymal stem cells properties. WST-1 proliferation assay data showed no significant difference between the proliferation rate of either cells following hUCS and FBS supplementation. Trypan blue exclusion dye test also revealed no significant difference for viability between hUCS and FBS groups. A significant difference was detected between the proliferation rate of stem cells cultured in serum-supplemented medium compared with serum-free medium. Conclusion: Our results indicate that human umbilical cord serum can effectively support proliferation of hBM-MSCS and hUC-MSCs in vitro and can be used as an appropriate substitute for FBS, especially in clinical studies. PMID:27738658

  8. The effect of Propionibacterium acnes on maturation of dendritic cells derived from acne patients' peripherial blood mononuclear cells.

    Science.gov (United States)

    Michalak-Stoma, Anna; Tabarkiewicz, Jacek; Olender, Alina; Juszkiewicz-Borowiec, Maria; Stoma, Filip; Pietrzak, Aldona; Pozarowski, Piotr; Bartkowiak-Emeryk, Małgorzata

    2008-01-01

    Propionibacterium acnes (P. acnes) has been implicated in the pathogenesis of acne vulgaris which is the most common cutaneous disorder. It has a proinflammatory activity and takes part in immune reactions modulating the Th1/Th2 cellular response. The exposure of dendritic cells (DCs) to whole bacteria, their components, cytokines or other inflammatory stimuli and infectious agents induces differentiation from immature DCs into antigen-presenting mature DCs. The aim of the study was to evaluate the capability of P. acnes to induce the maturation of DCs. We stimulated monocyte derived dendritic cells (Mo-DCs) from acne patients with various concetrations of heat-killed P. acnes (10(6)-10(8) bacteria/ml) cultured from acne lesions. The results showed an increase in CD80+/CD86+/DR+ and CD83+/CD1a+/DR+ cells percentage depending on the concetration of P. acnes. The expression of CD83 and CD80 (shown as the mean fluorescence intensity - MFI) increased with higher concetrations of P. acnes. There were also significant correlations between MFI of CD83, CD80, CD86 and concetration of P. acnes. The study showed that P. acnes in the concetration of 10(8) bacteria/ml is most effective in the induction of Mo-DCs maturation. Futher studies concerning the influence on the function of T cells are needed.

  9. The effect of Propionibacterium acnes on maturation of dendritic cells derived from acne patients' peripherial blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Maria Juszkiewicz-Borowiec

    2009-01-01

    Full Text Available Propionibacterium acnes (P. acnes has been implicated in the pathogenesis of acne vulgaris which is the most common cutaneous disorder. It has a proinflammatory activity and takes part in immune reactions modulating the Th1/Th2 cellular response. The exposure of dendritic cells (DCs to whole bacteria, their components, cytokines or other inflammatory stimuli and infectious agents induces differentiation from immature DCs into antigen-presenting mature DCs. The aim of the study was to evaluate the capability of P. acnes to induce the maturation of DCs. We stimulated monocyte derived dendritic cells (Mo-DCs from acne patients with various concetrations of heat-killed P. acnes (10(6-10(8 bacteria/ml cultured from acne lesions. The results showed an increase in CD80+/CD86+/DR+ and CD83+/CD1a+/DR+ cells percentage depending on the concetration of P. acnes. The expression of CD83 and CD80 (shown as the mean fluorescence intensity - MFI increased with higher concetrations of P. acnes. There were also significant correlations between MFI of CD83, CD80, CD86 and concetration of P. acnes. The study showed that P. acnes in the concetration of 10(8 bacteria/ml is most effective in the induction of Mo-DCs maturation. Futher studies concerning the influence on the function of T cells are needed.

  10. Transplantation of human umbilical cord blood-derived mononuclear cells induces recovery of motor dysfunction in a rat model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-04-01

    Full Text Available Chao Chen,1,* Jing Duan,1,* Aifang Shen,2,* Wei Wang,1 Hao Song,1 Yanming Liu,1 Xianjie Lu,1 Xiaobing Wang,2 Zhiqing You,1 Zhongchao Han,3,4 Fabin Han1 1Center for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 2Department of Gynecology and Obstetrics, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 3The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Peking Union of Medical College, Tianjin, People's Republic of China; 4National Engineering Research Center of Cell Products, AmCellGene Co. Ltd., TEDA, Tianjin, People's Republic of China*These authors contributed equally to this workAbstract: Human umbilical cord blood-derived mononuclear cells (hUCB-MNCs were reported to have neurorestorative capacity for neurological disorders such as stroke and traumatic brain injury. This study was performed to explore if hUCB-MNC transplantation plays any therapeutic effects for Parkinson's disease (PD in a 6-OHDA-lesioned rat model of PD. hUCB-MNCs were isolated from umbilical cord blood and administered to the striatum of the 6-OHDA-lesioned rats. The apomorphine-induced locomotive turning-overs were measured to evaluate the improvement of motor dysfunctions of the rats after administration of hUCB-MNCs. We observed that transplanted hUCB-MNCs significantly improve the motor deficits of the PD rats and that grafted hUCB-MNCs integrated to the host brains and differentiated to neurons and dopamine neurons in vivo after 16 weeks of transplantation. Our study provided evidence that transplanted hUCB-MNCs play therapeutic effects in a rat PD model by differentiating to neurons and dopamine neurons. Keywords: hUCB-MNCs, Parkinson's disease, transplantation

  11. Monocyte-derived dendritic cells enhance cell proliferation and porcine circovirus type 2 replication in concanavalin A-stimulated swine peripheral blood lymphocytes in vitro.

    Science.gov (United States)

    Lin, Chun-Ming; Jeng, Chian-Ren; Hsiao, Shih-Hsuan; Lee, Yao; Tsai, Yi-Chieh; Chia, Mi-Yuan; Pang, Victor Fei

    2012-01-15

    Dendritic cells (DCs) are professional antigen presenting cells cooperating with other immune cells for the activation of innate and adaptive immune responses. The objective of the present study was to investigate the replication activity of porcine circovirus type 2 (PCV2) in DCs and/or lymphocytes during their cross talk and its possible mechanism. Two models were set, herein. Swine blood monocyte (Mo)-derived DCs (MoDCs) or peripheral blood lymphocytes (PBLs) were inoculated with PCV2 prior to their co-cultivation. Bacterial lipopolysaccharide (LPS) and concanavalin A (Con A) were used to stimulate MoDCs and PBLs, respectively. During 6 days of cultivation, a high PCV2 antigen-containing rate without detectable intranuclear signals and a slight but significant increase in the copy number of PCV2 genome were detected in PCV2-inoculated MoDCs. The presence of LPS alone or PCV2-free PBLs, however, had no effect on the location of PCV2 antigens or copy number of PCV2 genome in PCV2-inoculated MoDCs. On the contrary, active PCV2 replication occurred in Con A-stimulated PCV2-inoculated PBLs. When compared with blood Mos, MoDCs induced significantly higher cell proliferation and intensified PCV2 replication in Con A-stimulated PCV2-inoculated PBLs, for which direct contact between MoDCs and lymphocytes was required. Among the cytokines secreted by Con A-activated PBLs, interleukin (IL)-2, but not IL-4 or interferon-γ, could induce cell proliferation and PCV2 replication in PCV2-inoculated PBLs. The findings suggest that although MoDCs support only limited PCV2 replication in themselves, their accessory cell function is required for cell proliferation and PCV2 replication in PCV2-infected lymphocytes.

  12. Effect of insulin on functional status of cord blood-derived dendritic cells and on dendritic cell-induced CTL cytotoxicity against pancreatic cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Qiu-Liang Liu; Yi-Sheng Wang; Jia-Xiang Wang

    2009-01-01

    BACKGROUND: Dendritic cells (DCs) are the most important antigen-presenting cells in the human body, and DCs with different mature status possess different or even opposite functions. This study was designed to explore the influence of insulin on the functional status of cord blood-derived DCs and on DC-induced cytotoxic T lymphocyte (CTL) activity against pancreatic cancer cell lines. METHODS: Mononuclear cells were isolated from fresh cord blood. Interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were used to induce or stimulate the mononuclear cells. Insulin at different concentrations served to modify DCs, and then DC morphology, number, and growth status were assessed. The DC immunophenotype was detected with a flow cytometer. The IL-12 in DC supernatant was determined by ELISA. DC functional status was evaluated by the autologous mixed lymphocyte reaction. T lymphocytes were induced by insulin-modified DCs to become CTLs. The CTL cytotoxicity against pancreatic cancer cell lines was determined. RESULTS:  Mononuclear cells from cord blood can be differentiated into DCs by cytokine induction and insulin modification. With the increase in insulin concentration (2.5-25 mg/L), the expression of DC HLA-DR, CD1α, CD80, and CD83 was significantly increased, the DC ability to secrete IL-12 was significantly improved, DC function to activate autologous lymphocytes was significantly enhanced, and the cytotoxicity of CTLs induced by insulin-modified DCs against pancreatic cancer cell lines was significantly strengthened. CONCLUSIONS: Insulin may facilitate DC induction and maturation, and improve the reproductive activity of autologous lymphocytes. The cytotoxicity of CTLs induced by insulin-modified DCs against pancreatic cancer cell lines was significantly enhanced. Insulin may serve as a factor modifying DCs and inducing CTLs in vitro in insulin biotherapy.

  13. Specific Accumulation of Tumor-Derived Adhesion Factor in Tumor Blood Vessels and in Capillary Tube-Like Structures of Cultured Vascular Endothelial Cells

    Science.gov (United States)

    Akaogi, Kotaro; Okabe, Yukie; Sato, Junji; Nagashima, Yoji; Yasumitsu, Hidetaro; Sugahara, Kazuyuki; Miyazaki, Kaoru

    1996-08-01

    Tumor-derived adhesion factor (TAF) was previously identified as a cell adhesion molecule secreted by human bladder carcinoma cell line EJ-1. To elucidate the physiological function of TAF, we examined its distribution in human normal and tumor tissues. Immunochemical staining with an anti-TAF monoclonal antibody showed that TAF was specifically accumulated in small blood vessels and capillaries within and adjacent to tumor nests, but not in those in normal tissues. Tumor blood vessel-specific staining of TAF was observed in various human cancers, such as esophagus, brain, lung, and stomach cancers. Double immunofluorescent staining showed apparent colocalization of TAF and type IV collagen in the vascular basement membrane. In vitro experiments demonstrated that TAF preferentially bound to type IV collagen among various extracellular matrix components tested. In cell culture experiments, TAF promoted adhesion of human umbilical vein endothelial cells to type IV collagen substrate and induced their morphological change. Furthermore, when the endothelial cells were induced to form capillary tube-like structures by type I collagen, TAF and type IV collagen were exclusively detected on the tubular structures. The capillary tube formation in vitro was prevented by heparin, which inhibited the binding of TAF to the endothelial cells. These results strongly suggest that TAF contributes to the organization of new capillary vessels in tumor tissues by modulating the interaction of endothelial cells with type IV collagen.

  14. Transport of Glial Cell Line-Derived Neurotrophic Factor into Liposomes across the Blood-Brain Barrier: In Vitro and in Vivo Studies

    Directory of Open Access Journals (Sweden)

    Shaoling Wu

    2014-02-01

    Full Text Available Glial cell line-derived neurotrophic factor (GDNF was encapsulated into liposomes in order to protect it from enzyme degradation in vivo and promote its permeability across the blood-brain barrier (BBB. In this study, GDNF conventional liposomes (GDNF-L and GDNF target sterically stabilized liposomes (GDNF-SSL-T were prepared. The average size of liposomes was below 90 nm. A primary model of BBB was established and evaluated by transendothelial electrical resistance (TEER and permeability. This BBB model was employed to study the permeability of GDNF liposomes in vitro. The results indicated that the liposomes could enhance transport of GDNF across the BBB and GDNF-SSL-T had achieved the best transport efficacy. The distribution of GDNF liposomes was studied in vivo. Free GDNF and GDNF-L were eliminated rapidly in the circulation. GDNF-SSL-T has a prolonged circulation time in the blood and favorable brain delivery. The values of the area under the curve (AUC(0–1 h in the brain of GDNF-SSL-T was 8.1 times and 6.8 times more than that of free GDNF and GDNF-L, respectively. These results showed that GDNF-SSL-T realized the aim of targeted delivery of therapeutic proteins to central nervous system.

  15. Transport of glial cell line-derived neurotrophic factor into liposomes across the blood-brain barrier: in vitro and in vivo studies.

    Science.gov (United States)

    Wu, Shaoling; Li, Guoqi; Li, Xiao; Lin, Caina; Yu, Ding; Luan, Shuo; Ma, Chao

    2014-02-27

    Glial cell line-derived neurotrophic factor (GDNF) was encapsulated into liposomes in order to protect it from enzyme degradation in vivo and promote its permeability across the blood-brain barrier (BBB). In this study, GDNF conventional liposomes (GDNF-L) and GDNF target sterically stabilized liposomes (GDNF-SSL-T) were prepared. The average size of liposomes was below 90 nm. A primary model of BBB was established and evaluated by transendothelial electrical resistance (TEER) and permeability. This BBB model was employed to study the permeability of GDNF liposomes in vitro. The results indicated that the liposomes could enhance transport of GDNF across the BBB and GDNF-SSL-T had achieved the best transport efficacy. The distribution of GDNF liposomes was studied in vivo. Free GDNF and GDNF-L were eliminated rapidly in the circulation. GDNF-SSL-T has a prolonged circulation time in the blood and favorable brain delivery. The values of the area under the curve (AUC(0-1 h)) in the brain of GDNF-SSL-T was 8.1 times and 6.8 times more than that of free GDNF and GDNF-L, respectively. These results showed that GDNF-SSL-T realized the aim of targeted delivery of therapeutic proteins to central nervous system.

  16. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Li, X.L. [Department of Dermatology, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); He, X.J. [Department of Orthopedics, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Wu, B.J.; Xu, M. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Chang, H.M. [Department of Otolaryngology - Head and Neck Surgery, Affiliated Hospital of Xi' an Medical University, Xi' an (China); Zhang, X.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Xing, Z. [Department of Clinical Dentistry, Faculty of Dentistry, Center for Clinical Dental Research, University of Bergen, Bergen (Norway); Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China)

    2014-03-18

    SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

  17. Concise review: ex vivo expansion of cord blood-derived hematopoietic stem and progenitor cells: basic principles, experimental approaches, and impact in regenerative medicine.

    Science.gov (United States)

    Flores-Guzmán, Patricia; Fernández-Sánchez, Verónica; Mayani, Hector

    2013-11-01

    Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play key roles in the production of mature blood cells and in the biology and clinical outcomes of hematopoietic transplants. The numbers of these cells, however, are extremely low, particularly in umbilical cord blood (UCB); thus, ex vivo expansion of human UCB-derived HSCs and HPCs has become a priority in the biomedical field. Expansion of progenitor cells can be achieved by culturing such cells in the presence of different combinations of recombinant stimulatory cytokines; in contrast, expansion of actual HSCs has proved to be more difficult because, in addition to needing recombinant cytokines, HSCs seem to deeply depend on the presence of stromal cells and/or elements that promote the activation of particular self-renewal signaling pathways. Hence, there is still controversy regarding the optimal culture conditions that should be used to achieve this. To date, UCB transplants using ex vivo-expanded cells have already been performed for the treatment of different hematological disorders, and although results are still far from being optimal, the advances are encouraging. Recent studies suggest that HSCs may also give rise to nonhematopoietic cells, such as neural, cardiac, mesenchymal, and muscle cells. Such plasticity and the possibility of producing nonhematopoietic cells at the clinical scale could bring new alternatives for the treatment of neural, metabolic, orthopedic, cardiac, and neoplastic disorders. Once standardized, ex vivo expansion of human HSCs/HPCs will surely have a positive impact in regenerative medicine.

  18. Down-regulation of pigment epithelium-derived factor in uveitic lesion associates with focal vascular endothelial growth factor expression and breakdown of the blood-retinal barrier.

    Science.gov (United States)

    Deeg, Cornelia A; Altmann, Frank; Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; Stangassinger, Manfred; Ueffing, Marius

    2007-05-01

    Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye. Identifying biological markers or pathways associated with this disease may allow the understanding of its pathogenesis at a molecular level. The vitreous is the body fluid closest to the disease-affected tissue and possibly also an effector of pathological processes relevant for ERU. Surgical removal of vitreous leads to cessation of relapses in spontaneous uveitis of both man and horse, therefore vitreous composites are likely to contribute to disease progression. Uveitic vitreous is likely to contain potential biomarkers in relatively undiluted quantities. With the goal to identify these markers, we systematically compared vitreous from healthy and disease-affected eyes by proteomic profiling. Nine differentially expressed proteins were identified, that are functionally related to immune response, inflammation, and maintenance of the blood-retinal barrier. One of these, pigment epithelium-derived factor, a protein involved in maintaining a proper blood-retina barrier as well as protecting from neoangiogenesis was additionally found to be down-regulated within uveitic retinal lesions whereas, conversely, vascular endothelial growth factor was found to be up-regulated at these sites. Together, these changes point to as of yet undiscovered biological pathways involved in the pathogenesis of this autoimmune disease.

  19. A filtration-based protocol to isolate human plasma membrane-derived vesicles and exosomes from blood plasma.

    Science.gov (United States)

    Grant, Ryan; Ansa-Addo, Ephraim; Stratton, Dan; Antwi-Baffour, Samuel; Jorfi, Samireh; Kholia, Sharad; Krige, Lizelle; Lange, Sigrun; Inal, Jameel

    2011-08-31

    The methods of Plasma Membrane-derived Vesicle (PMV) isolation and quantification vary considerably in the literature and a new standard needs to be defined. This study describes a novel filtration method to isolate PMVs in plasma, which avoids high speed centrifugation, and to quantify them using a Becton Dickinson (BD) FACS Calibur™ flow cytometer, as annexin V-positive vesicles, larger than 0.2 μm in diameter. Essentially microvesicles (which comprise a mixture of PMVs and exosomes) from citrate plasma were sonicated to break up clumped exosomes, and filtered using Millipore 0.1 μm pore size Hydrophilic Durapore membranes in Swinnex 13 mm filter holders. Phosphatidylserine-positive PMVs detected with annexin V-PE were quantified using combined labelling and gating strategies in conjunction with Polysciences Polybead Microspheres (0.2 μm) and BDTrucount tubes. The PMV absolute count was calculated on the analysis template using the Trucount tube lot number information and expressed in PMV count/ml. Having estimated a normal reference range (0.51×10(5)-2.82×10(5) PMVs/ml) from a small sample of human donors, using the developed method, the effect of certain variables was investigated. Variations such as freezing of samples and gender status did not significantly alter the PMV absolute count, and with age plasma PMV levels were only marginally reduced. Smokers appeared to have reduced PMV levels. Nicotine, as for calpeptin was shown to dose-dependently (from 10 up to 50 μM) reduce levels of early apoptosis in THP-1 monocytes and to decrease the level of PMV release. Fasting individuals had 2-3 fold higher PMV absolute counts compared to non-fasting subjects.

  20. Immunologic testing of xeno-derived osteochondral grafts using peripheral blood mononuclear cells from healthy human donors

    Directory of Open Access Journals (Sweden)

    Targoni Oleg S

    2005-06-01

    Full Text Available Abstract Background One means of treating osteoarthritis is with autologous or allogeneic osteochondral grafts. The purpose of this study was to evaluate the innate immunological response in humans toward xeno-derived osteochondral grafts that have been partially or entirely treated by the photooxidation process. Methods The antigens tested included bovine, porcine, ovine and equine osteochondral samples that have been treated in successive steps of photooxidation. ELISPOT assays were used to evaluate the production of IL-1, IL-4, IL-6, IL-10, IL-12 and TNF-α by human monocytes in response to the antigens. Results Results indicated vigorous production of IL-1, IL-6, IL-10 and TNF-α in response to untreated bovine, porcine and equine specimens. This indicates that these samples are perceived as foreign, or stimulatory, by the human monocytes. There was no induction of IL-4 or IL-12, which is required for Th2 and Th1 immunity, respectively. In contrast, the processed bovine, porcine and equine samples did not induce significant activation of cells of the innate immune system. This occurred after the first step in processing (after cleaning in increasing strengths of ethanol. This suggests that the processing steps dramatically, if not completely, negated the immunostimulatory properties of the test sample. The results for the ovine samples indicate a reverse response. Conclusion The findings of the study suggest that photooxidized bovine, porcine or equine samples have the potential to be used as an osteochondral graft. Although the first step in processing reduced the immunological response, photooxidation is still necessary to retain the structure and mechanical integrity of the cartilage, which would allow for immediate joint resurfacing.

  1. Synergistic Effect of Sodium Butyrate and Thalidomide in the Induction of Fetal Hemoglobin Expression in Erythroid Progenitors Derived from Cord Blood CD133 + Cells

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    Ali Dehghanifard

    2012-07-01

    Full Text Available Background: The use of drugs with the ability to induce production of fetal hemoglobin as a novel therapeutic approach in treating β-Hemoglobinopathies is considered. γ-globin gene expression inducer drugs including sodium butyrate and thalidomide can reduce additional α-globin chains accumulation in erythroid precursors. Materials and Methods: In this experimental study, MACS kit was used to isolate CD133+ cells of umbilical cord blood. Further, the effect of two drugs of thalidomide and sodium butyrate were separately and combined studied on the induction of quantitative expression of β-globin and γ-globin genes in erythroid precursor cells derived from CD133+ stem cells in-vitro. For this purpose, the technique SYBR green Real-time PCR was used.Results: Flow cytometry results showed that approximately 95% of purified cells were CD133+. Real-time PCR results also showed the increased levels of γ-globin mRNA in the cell groups treated with thalidomide, sodium butyrate and combination of drugs as 2.6 and 1.2 and 3.5 times respectively, and for β-globin gene, it is respectively 1.4 and 1.3 and 1.6 times compared with the control group (p<0.05.Conclusion: The study results showed that the mentioned drug combination can act as a pharmaceutical composition affecting the induction of fetal hemoglobin expression in erythroid precursor cells derived from CD133 + cells.

  2. Response to intravenous allogeneic equine cord-blood-derived mesenchymal stromal cells administered from chilled or frozen state in serum and protein free media

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    Lynn Brandon Williams

    2016-07-01

    Full Text Available Equine Mesenchymal stromal cells (MSC are commonly transported, chilled or frozen, to veterinary clinics. These MSC must remain viable and minimally affected by culture, transport, or injection processes. The safety of two carrier solutions developed for optimal viability and excipient use were evaluated in ponies, with and without allogeneic cord blood-derived (CB MSC. We hypothesized that neither the carrier solutions nor CB-MSC would elicit measurable changes in clinical, hematological, or biochemical parameters. In 9 ponies (study 1 a bolus of HypoThermosol® FRS (HTS-FRS, CryoStor® CS10 (CS10 or saline was injected IV (n=3/treatment. Study 2, following a one week washout period 5x107 pooled allogeneic CB-MSC were administered IV in HTS-FRS following 24h simulated chilled transport. Study 3, following another one week washout period 5x107 pooled allogeneic CB-MSC were administered IV in CS10 immediately after thawing. Nine ponies received CB-MSCs in study 2 and 3 and three ponies received the cell carrier media without cells. CB-MSCs were pooled in equal numbers from five unrelated donors. In all studies ponies were monitored with physical examination, and blood collection for 7 days following injection. CD4 and CD8 lymphocyte populations were also evaluated in each blood sample.In all three studies, physical exam, complete blood cell count, serum biochemistry, and coagulation panel did not deviate from established normal ranges. Proportions of CD4+ and CD8+ lymphocytes increased at 168h post injection in CB-MSC treatment groups regardless of the carrier solution. Decreases in CD4+/CD8+ double positive populations were observed at 24 h and 72 h in CB-MSC treated animals. There was no difference in viability between CB-MSC suspended in HTS-FRS or CS10.HTS-FRS and CS10 used for low volume excipient injection of MSC suspensions was not associated with short-term adverse reactions. HTS-FRS and CS10 both adequately maintain CB-MSC viability

  3. Proliferation and apoptosis property of mesenchymal stem cells derived from peripheral blood under the culture conditions of hypoxia and serum deprivation

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    FU Wei-li; JIA Zhu-qing; WANG Wei-ping; ZHANG Ji-ying; FU Xin; DUAN Xiao-ning; LEUNG Kevin Kar Ming; ZHOU Chun-yan; YU Jia-kuo

    2011-01-01

    Background The proliferation and apoptosis property of mesenchymal stem cells derived from peripheral blood (PB-MSCs) were investigated under hypoxia and serum deprivation conditions in vitro so as to evaluate the feasibility for autologous PB-MSCs applications in cartilage repair.Methods MSCs were mobilized into peripheral blood by granulocyte colony stimulating factor (G-CSF) and AMD3100.The blood samples were collected from central ear artery of rabbits.Adhered cells were obtained by erythrocyte lysis buffer and identified as MSCs by adherence to plastic,spindle shaped morphology,specific surface markers,differentiation abilities into osteoblasts,adipocytes and chondroblasts in vitro under appropriate conditions.MSCs were cultured in four groups at different oxygen tension (20% O2 and 2% O2),with or without 10% fetal bovine serum (FBS)conditions:20% O2 and 10% FBS complete medium (normal medium,N),20% O2 and serum deprivation medium (D),2% O2 and 10% FBS complete medium (hypoxia,H),2% O2 and serum deprivation (HD).Cell proliferation was determined by CCK-8 assay.Apoptosis was detected by Annexin V/Pl and terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL) staining.Results Spindle-shaped adherent cells were effectively mobilized from peripheral blood by a combined administration of G-CSF plus AMD3100.These cells showed typical fibroblast-like phenotype similar to MSCs from bone marrow (BM-MSCs),and expressed a high level of typical MSCs markers CD29 and CD44,but lacked in the expression of hematopoietic markers CD45 and major histocompatibility complex Class Ⅱ (MHC Ⅱ).They could also differentiate into osteoblasts,adipocytes and chondroblasts in vitro under appropriate conditions.No significant morphological differences were found among the four groups.It was found that hypoxia could enhance proliferation of PB-MSCs regardless of serum concentration,but serum deprivation inhibited proliferation at the later stage of culture

  4. Fibroblast growth factor-4 and hepatocyte growth factor induce differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Xin-Qin Kang; Wei-Jin Zang; Li-Jun Bao; Dong-Ling Li; Tu-Sheng Song; Xiao-Li Xu; Xiao-Jiang Yu

    2005-01-01

    AIM: To investigate the differentiation of human umbilical cord blood (HUCB)-derived mesenchymal stem cells (MSCs) into hepatocytes by induction of fibroblast growth factor-4 (FGF-4) and hepatocyte growth factor (HGF), and to find a new source of cell types for therapies of hepatic diseases.METHODS: vSCs were isolated by combining gradient density centrifugation with plastic adherence. When HUCB-derived MSCs reached 70% confluence, they were cultured in Iscove modified Dulbecco medium (IMDM) supplemented with 10 mL/L FBS, 20 ng/mL HGF and 10 ng/mL FGF-4. The medium was changed every 4 d and stored for albumin, alpha-fetoprotein (AFP) and urea assay. Expression of CK-18 was detected by immunocytochemistry. Glycogen storage in hepatocytes was determined by PAS staining.RESULTS: By combining gradient density centrifugation with plastic adherence, we could isolate MSCs from 25.6% of human umbilical cord blood. When MSCs were cultured with FGF-4 and HGF, approximately 63.6% of cells became small, round and epithelioid on d 28 by morphology. Compared with the control, the level of AFP increased significantly from d 12 to 18.20±1.16 μg/L (t = 2.884, P<0.05) in MSCs cultured with FGF-4 and HGF, and was higher (54.28±3.11 μg/L) on d 28 (t = 13.493, P<0.01). Albumin increased significantly on d 16 (t = 6.68, P<0.01) to 1.02±0.15 μg/mL, and to 3.63±0.30 μg/mL on d 28 (t = 11.748, P<0.01). Urea(4.72±1.03 μmol/L) was detected on d 20 (t = 4.272,P<0.01), and continued to increase to 10.28±1.06 μmol/L on d 28 (t = 9.276, P<0.01). Cells expressed CK-18 on d 16. Glycogen storage was observed on d 24. CONCLUSION: HUCB-derived MSCs can differentiate into hepatocytes by induction of FGF-4 and HGF. HUCBderived MSCs are a new source of cell types for cell transplantation therapy of hepatic diseases.

  5. Vascular smooth muscle G(q) signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension.

    Science.gov (United States)

    Harris, David M; Cohn, Heather I; Pesant, Stéphanie; Zhou, Rui-Hai; Eckhart, Andrea D

    2007-11-01

    More than 30% of the US population has high blood pressure (BP), and less than a third of people treated for hypertension have it controlled. In addition, the etiology of most high BP is not known. Having a better understanding of the mechanisms underlying hypertension could potentially increase the effectiveness of treatment. Because G(q) signaling mediates vasoconstriction and vascular function can cause BP abnormalities, we were interested in determining the role of vascular smooth muscle (VSM) G(q) signaling in two divergent models of hypertension: a renovascular model of hypertension through renal artery stenosis and a genetic model of hypertension using mice with VSM-derived high BP. Inhibition of VSM G(q) signaling attenuated BP increases induced by renal artery stenosis to a similar extent as losartan, an ANG II receptor blocker and current antihypertensive therapy. Inhibition of G(q) signaling also attenuated high BP in our genetic VSM-derived hypertensive model. In contrast, BP remained elevated 25% following treatment with losartan, and prazosin, an alpha(1)-adrenergic receptor antagonist, only decreased BP by 35%. Inhibition of G(q) signaling attenuated VSM reactivity to ANG II and resulted in a 2.4-fold rightward shift in EC(50). We also determined that inhibition of G(q) signaling was able to reverse VSM hypertrophy in the genetic VSM-derived hypertensive model. These results suggest that G(q) signaling is an important signaling pathway in two divergent models of hypertension and, perhaps, optimization of antihypertensive therapy could occur with the identification of particular G(q)-coupled receptors involved.

  6. Measurements of diagnostic examination performance and correlation analysis using microvascular leakage, cerebral blood volume, and blood flow derived from 3T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in glial tumor grading

    Energy Technology Data Exchange (ETDEWEB)

    Server, Andres; Nakstad, Per H. [Oslo University Hospital-Ullevaal, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Oslo (Norway); Graff, Bjoern A. [Oslo University Hospital-Ullevaal, Department of Radiology and Nuclear Medicine, Oslo (Norway); Orheim, Tone E.D.; Gadmar, Oeystein B. [Oslo University Hospital, Interventional Centre, Oslo (Norway); Schellhorn, Till [Oslo University Hospital-Ullevaal, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); Josefsen, Roger [Oslo University Hospital-Ullevaal, Department of Neurosurgery, Oslo (Norway)

    2011-06-15

    To assess the diagnostic accuracy of microvascular leakage (MVL), cerebral blood volume (CBV) and blood flow (CBF) values derived from dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MR imaging) for grading of cerebral glial tumors, and to estimate the correlation between vascular permeability/perfusion parameters and tumor grades. A prospective study of 79 patients with cerebral glial tumors underwent DSC-MR imaging. Normalized relative CBV (rCBV) and relative CBF (rCBF) from tumoral (rCBVt and rCBFt), peri-enhancing region (rCBVe and rCBFe), and the value in the tumor divided by the value in the peri-enhancing region (rCBVt/e and rCBFt/e), as well as MVL, expressed as the leakage coefficient K{sub 2} were calculated. Hemodynamic variables and tumor grades were analyzed statistically and with Pearson correlations. Receiver operating characteristic (ROC) curve analyses were also performed for each of the variables. The differences in rCBVt and the maximum MVL (MVL{sub max}) values were statistically significant among all tumor grades. Correlation analysis using Pearson was as follows: rCBVt and tumor grade, r = 0.774; rCBFt and tumor grade, r = 0.417; MVL{sub max} and tumor grade, r = 0.559; MVL{sub max} and rCBVt, r = 0.440; MVL{sub max} and rCBFt, r = 0.192; and rCBVt and rCBFt, r = 0.605. According to ROC analyses for distinguishing tumor grade, rCBVt showed the largest areas under ROC curve (AUC), except for grade III from IV. Both rCBVt and MVL{sub max} showed good discriminative power in distinguishing all tumor grades. rCBVt correlated strongly with tumor grade; the correlation between MVL{sub max} and tumor grade was moderate. (orig.)

  7. Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension.

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    Jonathan A Rose

    Full Text Available Pulmonary arterial hypertension (PAH is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH.

  8. Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells

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    Zhao Yong

    2012-01-01

    Full Text Available Abstract Background Inability to control autoimmunity is the primary barrier to developing a cure for type 1 diabetes (T1D. Evidence that human cord blood-derived multipotent stem cells (CB-SCs can control autoimmune responses by altering regulatory T cells (Tregs and human islet β cell-specific T cell clones offers promise for a new approach to overcome the autoimmunity underlying T1D. Methods We developed a procedure for Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates lymphocytes from the whole blood and briefly co-cultures them with adherent CB-SCs before returning them to the patient's circulation. In an open-label, phase1/phase 2 study, patients (n = 15 with T1D received one treatment with the Stem Cell Educator. Median age was 29 years (range: 15 to 41, and median diabetic history was 8 years (range: 1 to 21. Results Stem Cell Educator therapy was well tolerated in all participants with minimal pain from two venipunctures and no adverse events. Stem Cell Educator therapy can markedly improve C-peptide levels, reduce the median glycated hemoglobin A1C (HbA1C values, and decrease the median daily dose of insulin in patients with some residual β cell function (n = 6 and patients with no residual pancreatic islet β cell function (n = 6. Treatment also produced an increase in basal and glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3 did not exhibit significant change at any follow-up. Individuals who received Stem Cell Educator therapy exhibited increased expression of co-stimulating molecules (specifically, CD28 and ICOS, increases in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3 cytokine balance. Conclusions Stem Cell Educator therapy is safe, and in individuals with moderate or severe T1D, a single treatment produces lasting improvement in metabolic control. Initial results indicate Stem Cell

  9. Chimerism of placenta-derived cells with maternal blood and umbilical cord blood cells%胎盘来源细胞与母血、脐血细胞的嵌合

    Institute of Scientific and Technical Information of China (English)

    莫峥; 盛宏霞; 韩忠朝; 徐曼; 田宠; 张斌; 陈虎

    2014-01-01

    背景:胎盘中含有丰富的细胞群,因其中 CD34+细胞含量高而受到越来越多学者的关注,有望成为临床造血干细胞移植治疗血液病及其他恶性疾病的新来源。  目的:探索胎盘来源细胞的数量、集落形成能力及其与母体的嵌合程度。  方法:采用健康足月剖腹产妇的胎盘,灌注法及组织块消化法收集胎盘中细胞;流式细胞仪检测胎盘及脐血中 CD34+细胞比例;培养细胞集落,定期观察集落形态并计数;序列特异性引物 PCR 扩增技术及序列特异性寡核苷酸探针方法检测胎盘、脐血和母亲外周血的HLA类型;短串联重复PCR方法检测胎盘细胞、脐血细胞和母亲外周血细胞的嵌合情况。  结果与结论:胎盘中 CD34+细胞数量明显优于脐血,且胎盘具有体外多种集落形成能力,集落形成良好,同时胎盘提取细胞中含有母体来源成分。提示胎盘中细胞数量及其基本生物学特性使其有潜力成为临床造血干细胞移植的新来源。%BACKGROUND:There are abundant cel populations in the placenta that attracts more and more attentions because of high content of CD34+cel s. It is expected to become a new source of hematopoietic stem cel s for the treatment of hematologic diseases and other malignant diseases. OBJECTIVE:To investigate the amount of cel s derived from placenta, their colony forming ability, and their chimerism analysis. METHODS:Five placentas obtained from five healthy ful-term cesarean women were treated with perfusion method and tissue digestion for the cel col ection. Flow cytometry was used to detect the proportion of CD34+cel s in the placenta and cord blood, fol owed by the culture of cel colonies as wel as regular observation of cel morphology and counting. PCR amplification with sequence-specific primers and sequence-specific oligonucleotide probes were used to examine HLA type of placenta, umbilical cord blood, and

  10. Identification of cord blood-derived mesenchymal stem/stromal cell populations with distinct growth kinetics, differentiation potentials, and gene expression profiles.

    Science.gov (United States)

    Markov, Vladimir; Kusumi, Kenro; Tadesse, Mahlet G; William, Dilusha A; Hall, Dorian M; Lounev, Vitali; Carlton, Arlene; Leonard, Jay; Cohen, Rick I; Rappaport, Eric F; Saitta, Biagio

    2007-02-01

    Phenotypic heterogeneity has been observed among mesenchymal stem/stromal cell (MSC) populations, but specific genes associated with this variability have not been defined. To study this question, we analyzed two distinct isogenic MSC populations isolated from umbilical cord blood (UCB1 and UCB2). The use of isogenic populations eliminated differences contributed by genetic background. We characterized these UCB MSCs for cell morphology, growth kinetics, immunophenotype, and potential for differentiation. UCB1 displayed faster growth kinetics, higher population doublings, and increased adipogenic lineage differentiation compared to UCB2. However, osteogenic differentiation was stronger for the UCB2 population. To identify MSC-specific genes and developmental genes associated with observed phenotypic differences, we performed expression analysis using Affymetrix microarrays and compared them to bone marrow (BM) MSCs. We compared UCB1, UCB2, and BM and identified distinct gene expression patterns. Selected clusters were analyzed demonstrating that genes of multiple developmental pathways, such as transforming growth factor-beta (TGF-beta) and wnt genes, and markers of early embryonic stages and mesodermal differentiation displayed significant differences among the MSC populations. In undifferentiated UCB1 cells, multiple genes were significantly up-regulated (p < 0.0001): peroxisome proliferation activated receptor gamma (PPARG), which correlated with adipogenic differentiation capacities, hepatocyte growth factor (HGF), and stromal-derived factor 1 (SDF1/CXCL12), which could both potentially contribute to the higher growth kinetics observed in UCB1 cells. Overall, the results confirmed the presence of two distinct isogenic UCB-derived cell populations, identified gene profiles useful to distinguish MSC types with different lineage differentiation potentials, and helped clarify the heterogeneity observed in these cells.

  11. Effects of hydrazine derivatives on vascular smooth muscle contractility, blood pressure and cGMP production in rats: comparison with hydralazine.

    Science.gov (United States)

    Vidrio, Horacio; Fernández, Gabriela; Medina, Martha; Alvarez, Ezequiel; Orallo, Francisco

    2003-01-01

    Hydralazine is a hydrazine derivative used clinically as a vasodilator and antihypertensive agent. Despite numerous studies with the drug, its mechanism of action has remained unknown; guanylate cyclase activation and release of endothelial relaxing factors are thought to be involved in its vasodilator effect. Other hydrazine derivatives are known to stimulate guanylate cyclase and could therefore share the vasodilator activity of hydralazine, although such possibility has not been assessed systematically. In the present study, hydralazine, hydrazine, phenylhydrazine, and isoniazid were evaluated for vascular smooth muscle relaxation in rat aortic rings with and without endothelium, as well as after incubation with the guanylate cyclase inhibitor methylene blue. They were also tested for enhancement of cyclic guanosine monophosphate (cGMP) production by cultured rat aortic smooth muscle cells and for hypotension in the anesthetized rat. All hydrazines relaxed aortic rings, an action unaffected by endothelium removal and, in all cases except hydralazine, antagonized by methylene blue. Only phenylhydrazine increased cGMP production and only hydralazine markedly lowered blood pressure. It was concluded that hydralazine vascular relaxation is independent of endothelium and is not related to guanylate cyclase activation. The other hydrazines studied also elicit endothelium-independent relaxation, but the effect is related to guanylate cyclase. The marked hypotensive effect of hydralazine contrasts with its modest relaxant activity and is not shared by the other hydrazines. The fact that hydrazine and isoniazid produce methylene blue-sensitive relaxation, yet do not enhance cGMP production suggests the need for activating factors present in aortic rings but not in isolated cells.

  12. Blood sugar test - blood

    Science.gov (United States)

    ... blood glucose level ( hypoglycemia ) may be due to: Hypopituitarism (a pituitary gland disorder) Underactive thyroid gland or ... tonic-clonic seizure Glucagon blood test Glucagonoma Hyperthyroidism Hypopituitarism Hypothyroidism Insulinoma Low blood sugar Multiple endocrine neoplasia ( ...

  13. Chondrogenic Differentiation of Human Umbilical Cord Blood-Derived Unrestricted Somatic Stem Cells on A 3D Beta-Tricalcium Phosphate-Alginate-Gelatin Scaffold

    Directory of Open Access Journals (Sweden)

    Masoud Soleimani

    2014-03-01

    Full Text Available Objective: Finding cell sources for cartilage tissue engineering is a critical procedure. The purpose of the present experimental study was to test the in vitro efficacy of the beta-tricalcium phosphate-alginate-gelatin (BTAG scaffold to induce chondrogenic differentiation of human umbilical cord blood-derived unrestricted somatic stem cells (USSCs. Materials and Methods: In this experimental study, USSCs were encapsulated in BTAG scaffold and cultured for 3 weeks in chondrogenic medium as chondrogenic group and in Dulbecco’s Modified Eagle’s Medium (DMEM as control group. Chondrogenic differentiation was evaluated by histology, immunofluorescence and RNA analyses for the expression of cartilage extracellular matrix components. The obtain data were analyzed using SPSS version 15. Results: Histological and immunohistochemical staining revealed that collagen II was markedly expressed in the extracellular matrix of the seeded cells on scaffold in presence of chondrogenic media after 21 days. Reverse transcription-polymerase chain reaction (RT-PCR showed a significant increase in expression levels of genes encoded the cartilage-specific markers, aggrecan, type I and II collagen, and bone morphogenetic protein (BMP-6 in chondrogenic group. Conclusion: This study demonstrates that BTAG can be considered as a suitable scaffold for encapsulation and chondrogenesis of USSCs.

  14. Low oxygen tension favored expansion and hematopoietic reconstitution of CD34(+) CD38(-) cells expanded from human cord blood-derived CD34(+) Cells.

    Science.gov (United States)

    Wang, Ziyan; Du, Zheng; Cai, Haibo; Ye, Zhaoyang; Fan, Jinli; Tan, Wen-Song

    2016-07-01

    Oxygen tension is an important factor that regulates hematopoietic stem cells (HSCs) in both in vivo hematopoietic microenvironment and ex vivo culture system. Although the effect of oxygen tension on ex vivo expansion of HSCs was extensively studied, there were no clear descriptions on physiological function and gene expression analysis of HSCs under different oxygen tensions. In this study, the effects of oxygen tension on ex vivo expansion characteristics of human umbilical cord blood (UCB)-derived CD34(+) cells are evaluated. Moreover, the physiological function of expanded CD34(+) cells was assessed by secondary expansion ability ex vivo and hematopoietic reconstitution ability in vivo. Also, genetic profiling was applied to analyze the expression of genes related to cell function. It was found that low oxygen tension favored expansion of CD34(+) CD38(-) cells. Additionally, CD34(+) cells expanded under low oxygen tension showed better secondary expansion ability and reconstitution ability than those under atmospheric oxygen concentration. Finally, the genetic profiling of CD34(+) CD38(-) cells cultured under low oxygen tension was more akin to freshly isolated cells. These results collectively demonstrate that low oxygen tension was able to better maintain both self-renewal and hematopoietic reconstitution potential and may lay an experimental basis for clinical transplantation of HSCs.

  15. Reaction of melatonin with hemoglobin-derived oxoferryl radicals and inhibition of the hydroperoxide-induced hemoglobin denaturation in red blood cells.

    Science.gov (United States)

    Tesoriere, L; Allegra, M; D'Arpa, D; Butera, D; Livrea, M A

    2001-09-01

    Melatonin has been shown to act as a radical scavenger in various chemical and biological model systems in vitro. Kinetic evidence is now provided showing that melatonin inhibits the irreversible degradation of hemoglobin (Hb), when incubated with red blood cells exposed to the oxidant activity of cumene hydroperoxide (cumOOH). A decrease of heme loss and accumulation of soluble methemoglobin (met-Hb) are explained in terms of the interaction of the indoleamine with perferryl Hb (Hb[Fe(IV)=O]), a highly reactive Hb-derived radical species responsible for the irreversible Hb degradation. A kinetic study, in pure chemical solution, showed that melatonin can effectively reduce the oxoferryl heme group of perferryl-Hb, thus forming met-Hb. The reducing activity of melatonin is of the same order as that of Trolox, the water-soluble vitamin E analog. This novel radical-scavenging activity of melatonin may contribute to the previously observed protective effects of melatonin in ischemia-reperfusion injury.

  16. Inhibition by miR-410 facilitates direct retinal pigment epithelium differentiation of umbilical cord blood-derived mesenchymal stem cells

    Science.gov (United States)

    Choi, Soon Won; Kim, Jae-Jun; Seo, Min-Soo; Park, Sang-Bum; Shin, Tae-Hoon; Shin, Ji-Hee; Seo, Yoojin; Kim, Hyung-Sik

    2017-01-01

    Retinal pigment epithelium (RPE) is a major component of the eye. This highly specialized cell type facilitates maintenance of the visual system. Because RPE loss induces an irreversible visual impairment, RPE generation techniques have recently been investigated as a potential therapeutic approach to RPE degeneration. The microRNA-based technique is a new strategy for producing RPE cells from adult stem cell sources. Previously, we identified that antisense microRNA-410 (anti-miR-410) induces RPE differentiation from amniotic epithelial stem cells. In this study, we investigated RPE differentiation from umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via anti-miR-410 treatment. We identified miR-410 as a RPE-relevant microRNA in UCB-MSCs from among 21 putative human RPE-depleted microRNAs. Inhibition of miR-410 induces overexpression of immature and mature RPE-specific factors, including MITF, LRAT, RPE65, Bestrophin, and EMMPRIN. The RPE-induced cells were able to phagocytize microbeads. Results of our microRNA-based strategy demonstrated proof-of-principle for RPE differentiation in UCB-MSCs by using anti-miR-410 treatment without the use of additional factors or exogenous transduction. PMID:27297412

  17. Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer's disease mouse model through modulation of neuroinflammation.

    Science.gov (United States)

    Lee, Hyun Ju; Lee, Jong Kil; Lee, Hyun; Carter, Janet E; Chang, Jong Wook; Oh, Wonil; Yang, Yoon Sun; Suh, Jun-Gyo; Lee, Byoung-Hee; Jin, Hee Kyung; Bae, Jae-Sung

    2012-03-01

    Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) have a potential therapeutic role in the treatment of neurological disorders, but their current clinical usage and mechanism of action has yet to be ascertained in Alzheimer's disease (AD). Here we report that hUCB-MSC transplantation into amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice significantly improved spatial learning and memory decline. Furthermore, amyloid-β peptide (Aβ) deposition, β-secretase 1 (BACE-1) levels, and tau hyperphosphorylation were dramatically reduced in hUCB-MSC transplanted APP/PS1 mice. Interestingly, these effects were associated with reversal of disease-associated microglial neuroinflammation, as evidenced by decreased microglia-induced proinflammatory cytokines, elevated alternatively activated microglia, and increased anti-inflammatory cytokines. These findings lead us to suggest that hUCB-MSC produced their sustained neuroprotective effect by inducing a feed-forward loop involving alternative activation of microglial neuroinflammation, thereby ameliorating disease pathophysiology and reversing the cognitive decline associated with Aβ deposition in AD mice.

  18. Modeling microbial ethanol production by E. coli under aerobic/anaerobic conditions: applicability to real postmortem cases and to postmortem blood derived microbial cultures.

    Science.gov (United States)

    Boumba, Vassiliki A; Kourkoumelis, Nikolaos; Gousia, Panagiota; Economou, Vangelis; Papadopoulou, Chrissanthy; Vougiouklakis, Theodore

    2013-10-10

    The mathematical modeling of the microbial ethanol production under strict anaerobic experimental conditions for some bacterial species has been proposed by our research group as the first approximation to the quantification of the microbial ethanol production in cases where other alcohols were produced simultaneously with ethanol. The present study aims to: (i) study the microbial ethanol production by Escherichia coli under controlled aerobic/anaerobic conditions; (ii) model the correlation between the microbial produced ethanol and the other higher alcohols; and (iii) test their applicability in: (a) real postmortem cases that had positive BACs (>0.10 g/L) and co-detection of higher alcohols and 1-butanol during the original ethanol analysis and (b) postmortem blood derived microbial cultures under aerobic/anaerobic controlled experimental conditions. The statistical evaluation of the results revealed that the formulated models were presumably correlated to 1-propanol and 1-butanol which were recognized as the most significant descriptors of the modeling process. The significance of 1-propanol and 1-butanol as descriptors was so powerful that they could be used as the only independent variables to create a simple and satisfactory model. The current models showed a potential for application to estimate microbial ethanol - within an acceptable standard error - in various tested cases where ethanol and other alcohols have been produced from different microbes.

  19. Targeted brain derived neurotropic factors (BDNF delivery across the blood-brain barrier for neuro-protection using magnetic nano carriers: an in-vitro study.

    Directory of Open Access Journals (Sweden)

    Sudheesh Pilakka-Kanthikeel

    Full Text Available Parenteral use of drugs; such as opiates exert immunomodulatory effects and serve as a cofactor in the progression of HIV-1 infection, thereby potentiating HIV related neurotoxicity ultimately leading to progression of NeuroAIDS. Morphine exposure is known to induce apoptosis, down regulate cAMP response element-binding (CREB expression and decrease in dendritic branching and spine density in cultured cells. Use of neuroprotective agent; brain derived neurotropic factor (BDNF, which protects neurons against these effects, could be of therapeutic benefit in the treatment of opiate addiction. Previous studies have shown that BDNF was not transported through the blood brain barrier (BBB in-vivo.; and hence it is not effective in-vivo. Therefore development of a drug delivery system that can cross BBB may have significant therapeutic advantage. In the present study, we hypothesized that magnetically guided nanocarrier may provide a viable approach for targeting BDNF across the BBB. We developed a magnetic nanoparticle (MNP based carrier bound to BDNF and evaluated its efficacy and ability to transmigrate across the BBB using an in-vitro BBB model. The end point determinations of BDNF that crossed BBB were apoptosis, CREB expression and dendritic spine density measurement. We found that transmigrated BDNF was effective in suppressing the morphine induced apoptosis, inducing CREB expression and restoring the spine density. Our results suggest that the developed nanocarrier will provide a potential therapeutic approach to treat opiate addiction, protect neurotoxicity and synaptic density degeneration.

  20. Biphasic influence of PGE2 on the resorption activity of osteoclast-like cells derived from human peripheral blood monocytes and mouse RAW264.7 cells.

    Science.gov (United States)

    Lutter, Anne-Helen; Hempel, Ute; Anderer, Ursula; Dieter, Peter

    2016-08-01

    Osteoclasts are large bone-resorbing cells of hematopoietic origin. Their main function is to dissolve the inorganic component hydroxyapatite and to degrade the organic bone matrix. Prostaglandin E2 (PGE2) indirectly affects osteoclasts by stimulating osteoblasts to release factors that influence osteoclast activity. The direct effect of PGE2 on osteoclasts is still controversial. To study the influence of PGE2 on osteoclast activity, human peripheral blood monocytes (hPBMC) and mouse RAW264.7 cells were cultured on osteoblast-derived extracellular matrix. hPBMC and RAW264.7 cells were differentiated by the addition of macrophage colony-stimulation factor and receptor activator of NFκB ligand and treated with PGE2 before and after differentiation induction. The pit area, an indicator of resorption activity, and the activity of tartrate-resistant acid phosphatase were dose-dependently inhibited when PGE2 was present ab initio, whereas the resorption activity remained unchanged when the cells were exposed to PGE2 from day 4 of culture. These results lead to the conclusion that PGE2 treatment inhibits only the differentiation of precursor osteoclasts whereas differentiated osteoclasts are not affected.

  1. Immunoregulation and human umbilical cord blood-derived mesenchymal stem cells transplantation%脐血间充质干细胞移植与免疫调节

    Institute of Scientific and Technical Information of China (English)

    焦保良; 王景川; 高炳华; 王新生

    2012-01-01

    BACKGROUND: Research in recent years suggests that the self-renewal and multi-directional differentiation potency of human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) offer basic condition to cell transplantation treatment. Moreover, their immunoloregulation function enormously expands the direction and limits cell transplantation treatment. OBJECTIVE: To retrospectively analyze the immunoloregulation and human UCB-MSCs transplantation. METHODS: The key word "umbilical cord blood-derived mesenchymal stem cells" was used to search in Pubmed database and CNKI database from January 2008 to June 2011 in English and Chinese using computer. The preliminary screening was made through reading the title and abstract. The articles with unrelated contents, repetitive and Meta analysis were excluded. 30 papers of pertinent literature to be published in the near future or published in the authority magazine were selected to review. RESULTS AND CONCLUSION: Human UCB-MSCs have the similar self-renewal and multi-directional differentiation potency with the bone marrow derived mesenchymal stem cells. Through cell transplantation technique, human UCB-MSCs show powerful potentiality in diabetes mellitus treatment, neural degeneration disease like Alzheimer's disease and Parkinson's disease and injury of nerve retreatment. Meanwhile, human UCB-MSCs have immunoregulatory ettects, they can lower immune reaction through down regulation of T-cells. We also get some advancements on several immunological diseases such as cell therapy of graft versus host disease and lupus nephritis.%背景:近年研究显示,脐血间充质干细胞的自我更新和多向分化潜能为细胞移植治疗提供了基础条件,而其免疫调节功能也极大地拓展了细胞治疗的方向和范围. 目的:就近期脐血间充质干细胞的免疫调节和细胞移植研究进行回顾分析. 摘要进行初筛,排除研究内容与此文无关的文献、重复性研究及Meta分析,

  2. Blood concentrations of hydroxychloroquine and its desethyl derivative correlate negatively with the percentage of CD45RO+ cells among CD4+ lymphocytes in hydroxychloroquine-treated lupus patients.

    Science.gov (United States)

    Sailler, Laurent; Puissant, Bénédicte; Méliani, Pascal; Castex, Jean Olivier; Saivin, Sylvie; Adoue, D; Fournie, B; Arlet, Philippe; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse; Pourrat, Jacques; Blancher, Antoine

    2007-06-01

    The objective of the study was to investigate the influence of the blood concentrations of hydroxychloroquine ([HCQ]) and its derivative desethylhydroxychloroquine ([DHCQ]) on lymphocyte activation or differentiation in HCQ-treated lupus patients. We studied the correlations between [HCQ], [DHCQ], and the frequency of various lymphocyte subsets in 58 HCQ-treated lupus patients (mean HCQ dose: 4.93 +/- 1.58 mg/kg/day; mean duration of the disease: 122 +/- 64 months). [HCQ] and [DHCQ] were determined by high-performance liquid chromatography (HPLC). Lymphocyte markers were studied by flow cytometry using monoclonal anti-CD3, -CD4, -CD8, -CD25, -DR, -CD45RA, -CD45RO, -CD19, -CD38, and -CD86 antibodies. sIL2-R serum concentrations were measured by enzyme-linked immunosorbent assay (ELISA). [HCQ] and [DHCQ] were 599.9 ng/mL (median: 529.5; range: 55-1935) and 353.43 (median: 286 ng/mL; range: 118-1090). In a multiple regression analysis, [HCQ] and [DHCQ] were associated with the HCQ prescribed dose in mg/kg/day (P = 0.0002 and P = 0.03) and with compliance to the treatment (P = 0.004 and P = 0.03). We found a negative correlation between [HCQ], [DHCQ], and the CD45RO+ cell frequency among CD3+CD4+ cells (P = 0.03 and P = 0.007, respectively). Other lymphocyte subset markers (LSMs) and sIL2-R concentrations were not significantly associated with [HCQ] or [DHCQ]. In the multiple regression analysis, CD45RO+ expression was negatively influenced by [HCQ] (P = 0.005), and positively influenced by smoking habits (P = 0.005) and age (P = 0.005). Similar results were found in the multivariate model including [DHCQ]. Disease activity and taking more than 10 mg/day of corticosteroids or an immunosuppressive drug did not influence CD45RO+ expression. Lupus patients had less CD3+CD4+CD45RO+ cells than controls (P = 0.03). In lupus patients, HCQ and DHCQ may alter the generation or the blood circulation of CD4+CD45RO+ lymphocytes in a concentration-dependent pattern.

  3. Neural differentiation of brain-derived neurotrophic factor-expressing human umbilical cord blood-derived mesenchymal stem cells in culture via TrkB-mediated ERK and β-catenin phosphorylation and following transplantation into the developing brain.

    Science.gov (United States)

    Lim, Jung Yeon; Park, Sang In; Kim, Seong Muk; Jun, Jin Ae; Oh, Ji Hyeon; Ryu, Chung Hun; Jeong, Chang Hyun; Park, Sun Hwa; Park, Soon A; Oh, Wonil; Chang, Jong Wook; Jeun, Sin-Soo

    2011-01-01

    The ability of mesenchymal stem cells (MSCs) to differentiate into neural cells makes them potential replacement therapeutic candidates in neurological diseases. Presently, overexpression of brain-derived neurotrophic factor (BDNF), which is crucial in the regulation of neural progenitor cell differentiation and maturation during development, was sufficient to convert the mesodermal cell fate of human umbilical cord blood-derived MSCs (hUCB-MSCs) into a neuronal fate in culture, in the absence of specialized induction chemicals. BDNF overexpressing hUCB-MSCs (MSCs-BDNF) yielded an increased number of neuron-like cells and, surprisingly, increased the expression of neuronal phenotype markers in a time-dependent manner compared with control hUCB-MSCs. In addition, MSCs-BDNF exhibited a decreased labeling for MSCs-related antigens such as CD44, CD73, and CD90, and decreased potential to differentiate into mesodermal lineages. Phosphorylation of the receptor tyrosine kinase B (TrkB), which is a receptor of BDNF, was increased significantly in MSC-BDNF. BDNF overexpression also increased the phosphorylation of β-catenin and extracellular signal-regulated kinases (ERKs). Inhibition of TrkB availability by treatment with the TrkB-specific inhibitor K252a blocked the BDNF-stimulated phosphorylation of β-catenin and ERKs, indicating the involvement of both the β-catenin and ERKs signals in the BDNF-stimulated and TrkB-mediated neural differentiation of hUCB-MSCs. Reduction of β-catenin availability using small interfering RNA-mediated gene silencing inhibited ERKs phosphorylation. However, β-catenin activation was maintained. In addition, inhibition of β-catenin and ERKs expression levels abrogated the BDNF-stimulated upregulation of neuronal phenotype markers. Furthermore, MSC-BDNF survived and migrated more extensively when grafted into the lateral ventricles of neonatal mouse brain, and differentiated significantly into neurons in the olfactory bulb and

  4. Humoral activity of cord blood-derived stem/progenitor cells: implications for stem cell-based adjuvant therapy of neurodegenerative disorders.

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    Edyta Paczkowska

    Full Text Available BACKGROUND: Stem/progenitor cells (SPCs demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs and their receptors in specific umbilical cord blood (UCB SPC populations, including lineage-negative, CD34(+, and CD133(+ cells, with that in unsorted, nucleated cells (NCs. METHODS AND RESULTS: The expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34(+, and CD133(+ cells. To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3 was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34(+, and CD133(+ cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34(+ or CD133(+ cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation. CONCLUSIONS: Collectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and

  5. Optimal Route for Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation to Protect Against Neonatal Hyperoxic Lung Injury: Gene Expression Profiles and Histopathology.

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    Dong Kyung Sung

    Full Text Available The aim of this study was to determine the optimal route of mesenchymal stem cell (MSC transplantation. To this end, gene expression profiling was performed to compare the effects of intratracheal (i.t. versus intravenous (i.v. MSC administration. Furthermore, the therapeutic efficacy of each route to protect against neonatal hyperoxic lung injury was also determined. Newborn Sprague-Dawley rats were exposed to hyperoxia (90% oxygen from birth for 14 days. Human umbilical cord blood-derived MSCs labeling with PKH26 were transplanted through either the i.t. (5×10(5 or i.v. (2×10(6 route at postnatal day (P 5. At P14, lungs were harvested for histological, biochemical and microarray analyses. Hyperoxic conditions induced an increase in the mean linear intercept and mean alveolar volume (MAV, indicative of impaired alveolarization. The number of ED-1 positive cells was significantly decreased by both i.t. and i.v. transplantations. However, i.t. administration of MSCs resulted in a greater decrease in MAV and ED-1 positive cells compared to i.v. administration. Moreover, the number of TUNEL-positive cells was significantly decreased in the i.t. group, but not in the i.v. group. Although the i.t. group received only one fourth of the number of MSCs that the i.v. group did, a significantly higher number of donor cell-derived red PKH 26 positivity were recovered in the i.t. group. Hyperoxic conditions induced the up regulation of genes associated with the inflammatory response, such as macrophage inflammatory protein-1 α, tumor necrosis factor-α and inter leukin-6; genes associated with cell death, such as p53 and caspases; and genes associated with fibrosis, such as connective tissue growth factor. In contrast, hyperoxic conditions induced the dwon-regulation of vascular endothelial growth factor and hepatocyte growth factor. These hyperoxia-induced changes in gene expression were decreased in the i.t. group, but not in the i.v. group. Thus

  6. Remarkable effect of mobile phase buffer on the SEC-ICP-AES derived Cu, Fe and Zn-metalloproteome pattern of rabbit blood plasma.

    Science.gov (United States)

    Jahromi, Elham Zeini; White, Wade; Wu, Qiao; Yamdagni, Raghav; Gailer, Jürgen

    2010-07-01

    The development of an analytical method to quantify the major Cu, Fe and Zn-containing metalloproteins in mammalian plasma has been recently reported. This method is based on the separation of plasma proteins by size exclusion chromatography (SEC) followed by the on-line detection of the metalloproteins by an inductively coupled plasma atomic emission spectrometer (ICP-AES). To assess whether the mobile phase buffer can affect the SEC-ICP-AES-derived metalloproteome pattern, thawed rabbit plasma was analyzed using phosphate buffered saline (PBS)-buffer (0.15 M, pH 7.4), Tris-buffer (0.1 and 0.05 M, pH 7.4), Hepes-buffer (0.1 M, pH 7.4) or Mops-buffer (0.1 M, pH 7.4). In contrast to the Cu-specific chromatograms, the Fe and Zn-specific chromatograms that were obtained with Tris, Hepes and Mops-buffer were considerably different from those attained with PBS-buffer. The Tris, Hepes and Mops-buffer mediated redistribution of ~25% plasma Zn(2+) from 100-600 kDa plasma proteins and to a smaller extent to a Hepes and Mops-buffer redistributed ~20% of plasma Fe(3+) from the 600 kDa elution range. Based on these results and considering that the utilization of PBS-buffer has previously resulted in the detection of a number of Cu, Fe and Zn-containing metalloentities in rabbit plasma that was most consistent with literature data, this mobile phase buffer is recommended for metallomic studies regarding mammalian blood plasma.

  7. Scanning electron microscopy of interaction of peripheral blood lymphocytes from colonic cancer patients with human colonic cancer-derived cells; P-4788.

    Directory of Open Access Journals (Sweden)

    Sugihara,Mutsuto

    1979-12-01

    Full Text Available Peripheral blood lymphocytes and the various lymphocyte fractions from patients with cancer of the colon were cultivated with target cells (P-4788 derived from the colon cancer. Changes in the surface ultrastructure during tumor cell destruction were studied by scanning electron microscopy (SEM. P-4788 cells adhering to the coverslip showed various surface activity. The surfaces of some cells were relatively flat; others were smooth or had fine granules. Still other cells were villous, round or had marked blebs. When host lymphocytes were added to the target cells, adhesion of the two cell groups began by many fine projections. After incubation for 6 h, some lymphocytes had adhered to the target cells. Many lymphocytes had adhered to the target tumor cells by 24--48 h incubation. Ultimately the tumor cells became swollen and disrupted. Most lymphocytes adherent to the target cells had few microvilli. Lymphocytes after elimination of phagocytes by carbonyl iron treatment also adhered readily. Some target cells showed adhesion with lymphocytes passed through nylon-wool columns, although the number of lymphocytes adhering was fewer than in the case of lymphocytes not passed through nylon-wool columns. T cells were collected from lymphocytes that form rosettes with SRBC by isolation with NH4Cl. They had markedly elongated microvilli which in places were sparsely scattered and tended to be localized on the side, a finding which suggests loss of cell activity by the time of SEM. Only a few T cells adhered to target cells and they seemed to be T cells without activity. It was thought that there are cytotoxic cells among T cells and that the co-existence of T cells, non-T cells and monocytes caused target cell destruction.

  8. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells.

    Science.gov (United States)

    Castillo-Melendez, Margie; Yawno, Tamara; Jenkin, Graham; Miller, Suzanne L

    2013-10-24

    In the research, clinical, and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however, this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical, and logistical considerations, together with the propensity for native cells to form teratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs), or umbilical cord blood (UCB) stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  9. Inhibitory effect of heparin-derived oligosaccharides on secretion of interleukin-4 and interleukin-5 from human peripheral blood T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Sheng-Li Ji; Hui-Fei Cui; Feng Shi; Yan-Qing Chi; Ji-Chao Cao; Mei-Yu Geng; Hua-Shi Guan

    2004-01-01

    AIM: To investigate the inhibitory effect of heparin-derived oligosaccharides (Oligs) on secretion of interleukin-4 (IL-4)and interleukin-5 (IL-5) from human peripheral blood T lymphocytes (PBTLs).METHODS: Oligs were prepared by three different heparin depolymerization methods and separated by gel filtration chromatography. PBTLs from ten adult patients with allergic eosinophilic gastroenteritis were treated with phytahematoagglutinin (PHA) and Oligs. The supernatants from the cell culture of PBTLs were harvested and subjected to the deterrnination of IL-4 and IL-5 contents by ELISA method.RESULTS: At the concentration of 5 μg/mL, Oligs with different Mr had different effects on the secretion of IL-4 and IL-5. The tetrasaccharide with Mr of 1 142, produced by depolymerizing heparin with hydrogen peroxide, had the strongest inhibitory effect on the secretion of IL-4. It decreased the IL-4 content from 375.6±39.2 ng/L (PHA group) to 12.5±5.7 ng/L (P<0.01). The hexasaccharide with Mr of 1 806, produced by depolymerizing heparin with β-elimination method, had the strongest inhibitory effect on the secretion of IL-5. It decreased the IL-5 content from 289.2±33.4 ng/L (PHA group) to 22.0±5.2 ng/L (P<0.01).CONCLUSION: The inhibitory activity of Oligs on the secretion of IL-4 and IL-5 from human PBTLs closely depends on their molecular structure, and there may be an essential structure to act as an inhibitor. The most effective inhibitors of IL-4 and IL-5 secretion are tetrasaccharides and hexasaccharides, respectively.

  10. Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients

    Science.gov (United States)

    Marini, Olivia; Spina, Cecilia; Mimiola, Elda; Cassaro, Adriana; Malerba, Giovanni; Todeschini, Giuseppe; Perbellini, Omar; Scupoli, Maria; Carli, Giuseppe; Facchinelli, Davide; Cassatella, Marco; Scapini, Patrizia; Tecchio, Cristina

    2016-01-01

    Human granulocytic myeloid-derived suppressor cells (G-MDSCs) have been described as low-density immunosuppressive CD66b+CD33dimHLA-DR-granulocytes that co-purify with mononuclear cells after density gradient centrifugation of blood from cancer patients. The role of G-MDSCs in Hodgkin (HL) and non-Hodgkin lymphoma (NHL) remains unclear. The percentage and immunophenotype of CD66b+CD33dimHLA-DR-cells were analyzed in PBMCs from HL and B-cell NHL patients (n = 124) and healthy donors (n = 48). The immunosuppressive functions of these cells were tested in vitro. Correlations between CD66b+CD33dimHLA-DR-cells and patient clinicopathological features and outcome, were evaluated. CD66b+CD33dimHLA-DR-cells were increased in PBMCs from HL and B-cell NHL patients as compared to healthy donors: 2.18 (0.02–70.92) vs 0.42 (0.04–2.97), p expression as compared to conventionally isolated (normal-density) autologous or healthy donor neutrophils. The in vitro depletion of CD66b+ cells from patient PBMCs restored the proliferation of autologous T cells. Higher frequencies of CD66b+CD33dimHLA-DR− G-MDSCs correlated significantly with unfavorable prognostic index scores and a shorter freedom from disease progression. PBMCs from HL and B-cell NHL patients contain a population of CD66b+CD33dimHLA-DR− G-MDSCs, mostly composed of activated low-density neutrophils with immunosuppressive properties. These findings disclose a previously unknown G-MDSC-mediated mechanism of immune-escape in lymphomas, therefore anticipating possible targets for therapeutic interventions. PMID:27050283

  11. Implication of NOD1 and NOD2 for the differentiation of multipotent mesenchymal stem cells derived from human umbilical cord blood.

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    Hyung-Sik Kim

    Full Text Available Toll-like receptors (TLRs and Nod-like receptors (NLRs are known to trigger an innate immune response against microbial infection. Although studies suggest that activation of TLRs modulate the function of mesenchymal stem cells (MSCs, little is known about the role of NLRs on the MSC function. In this study, we investigated whether NOD1 and NOD2 regulate the functions of human umbilical cord blood-derived MSCs (hUCB-MSCs. The genes of TLR2, TLR4, NOD1, and NOD2 were expressed in hUCB-MSCs. Stimulation with each agonist (Pam(3CSK(4 for TLR2, LPS for TLR4, Tri-DAP for NOD1, and MDP for NOD2 led to IL-8 production in hUCB-MSC, suggesting the expressed receptors are functional in hUCB-MSC. CCK-8 assay revealed that none of agonist influenced proliferation of hUCB-MSCs. We next examined whether TLR and NLR agonists affect osteogenic-, adipogenic-, and chondrogenic differentiation of hUCB-MSCs. Pam(3CSK(4 and Tri-DAP strongly enhanced osteogenic differentiation and ERK phosphorylation in hUCB-MSCs, and LPS and MDP also slightly did. Treatment of U0126 (MEK1/2 inhibitor restored osteogenic differentiation enhanced by Pam(3CSK(4. Tri-DAP and MDP inhibited adipogenic differentiation of hUCB-MSCs, but Pam(3CSK(4 and LPS did not. On chondrogenic differentiation, all TLR and NLR agonists could promote chondrogenesis of hUCB-MSCs with difference in the ability. Our findings suggest that NOD1 and NOD2 as well as TLRs are involved in regulating the differentiation of MSCs.

  12. Extracellular matrix gel is necessary for in vitro cultivation of insulin producing cells from human umbilical cord blood derived mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    GAO Feng; WU De-quan; HU Yan-hua; JIN Guang-xin

    2008-01-01

    Background Pancreatic islet cell transplantation is an effective approach to treat type 1 diabetes. However, this therapy is not widely used because of the severe shortage of transplantable donor islets. This study investigated whether mesenchymal stem cells (MSCs) derived from human umbilical cord blood (UCB) could be transdifferentiated into insulin producing cells in vitro and the role of extracellular matrix (ECM) gel in this procedure.Methods Human UCB samples were collected and MSCs were isolated. MSCs specific marker proteins were analyzed by a flow cytometer. The capacities of osteoblast and adipocyte to differentiate were tested. Differentiation into islet like cell was induced by a 15-day protocol with or without ECM gel. Pancreatic characteristics were evaluated with immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. Insulin content and release in response to glucose stimulation were detected with chemiluminescent immunoassay system.Results Sixteen MSCs were isolated from 42 term human UCB units (38%). Human UCB-MSCs expressed MSCs specific markers and could be induced in vitro into osteoblast and adipocyte. Islet like cell clusters appeared about 9 days after pancreatic differentiation in the inducing system with ECM gel. The insulin positive cells accounted for (25.2±3.4)% of the induced cells. The induced cells expressed islet related genes and hormones, but were not very responsive to glucose challenge. When MSCs were induced without ECM gel, clusters formation and secretion of functional islet proteins could not be observed.Conclusions Human UCB-MSCs can differentiate into islet like cells in vitro and ECM gel plays an important role in pancreatic endocrine cell maturation and formation of three dimensional structures.

  13. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells

    Directory of Open Access Journals (Sweden)

    Margie eCastillo-Melendez

    2013-10-01

    Full Text Available In the research, clinical and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical and logistical considerations, together with the propensity for native cells to form terratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs, or umbilical cord blood (UCB stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells and mesenchymal stem cells, and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  14. In Acute Stroke, Can CT Perfusion-Derived Cerebral Blood Volume Maps Substitute for Diffusion-Weighted Imaging in Identifying the Ischemic Core?

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    William A Copen

    Full Text Available In the treatment of patients with suspected acute ischemic stroke, increasing evidence suggests the importance of measuring the volume of the irreversibly injured "ischemic core." The gold standard method for doing this in the clinical setting is diffusion-weighted magnetic resonance imaging (DWI, but many authors suggest that maps of regional cerebral blood volume (CBV derived from computed tomography perfusion imaging (CTP can substitute for DWI. We sought to determine whether DWI and CTP-derived CBV maps are equivalent in measuring core volume.58 patients with suspected stroke underwent CTP and DWI within 6 hours of symptom onset. We measured low-CBV lesion volumes using three methods: "objective absolute," i.e. the volume of tissue with CBV below each of six published absolute thresholds (0.9-2.5 mL/100 g, "objective relative," whose six thresholds (51%-60% were fractions of mean contralateral CBV, and "subjective," in which two radiologists (R1, R2 outlined lesions subjectively. We assessed the sensitivity and specificity of each method, threshold, and radiologist in detecting infarction, and the degree to which each over- or underestimated the DWI core volume. Additionally, in the subset of 32 patients for whom follow-up CT or MRI was available, we measured the proportion of CBV- or DWI-defined core lesions that exceeded the follow-up infarct volume, and the maximum amount by which this occurred.DWI was positive in 72% (42/58 of patients. CBV maps' sensitivity/specificity in identifying DWI-positive patients were 100%/0% for both objective methods with all thresholds, 43%/94% for R1, and 83%/44% for R2. Mean core overestimation was 156-699 mL for objective absolute thresholds, and 127-200 mL for objective relative thresholds. For R1 and R2, respectively, mean±SD subjective overestimation were -11±26 mL and -11±23 mL, but subjective volumes differed from DWI volumes by up to 117 and 124 mL in individual patients. Inter-rater agreement

  15. Endothelial cells derived from the blood-brain barrier and islets of Langerhans differ in their response to the effects of bilirubin on oxidative stress under hyperglycemic conditions

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    Jaime eKapitulnik

    2012-07-01

    Full Text Available Unconjugated bilirubin (UCB is a neurotoxic degradation product of heme. Its toxic effects include induction of apoptosis, and ultimately neuronal cell death. However, at low concentrations, UCB is a potent antioxidant that may protect cells and tissues against oxidative stress by neutralizing toxic metabolites such as reactive oxygen species (ROS. High glucose levels (hyperglycemia generate reactive metabolites. Endothelial cell dysfunction, an early vascular complication in diabetes, has been associated with hyperglycemia-induced oxidative stress. Both glucose and UCB are substrates for transport proteins in microvascular endothelial cells of the blood-brain barrier (BBB. In the current study we show that UCB (1-40 M induces apoptosis and reduces survival of bEnd3 cells, a mouse brain endothelial cell line which serves as an in vitro model of the BBB. These deleterious effects of UCB were enhanced in the presence of high glucose (25 mM levels. Interestingly, the bEnd3 cells exhibited an increased sensitivity to the apoptotic effects of UCB when compared to the MS1 microcapillary endothelial cell line. MS1 cells originate from murine pancreatic islets of Langherans, and are devoid of the barrier characteristics of BBB-derived endothelial cells. ROS production was increased in both bEnd3 and MS1 cells exposed to high glucose, as compared with cells exposed to normal (5.5 mM glucose levels. While UCB (0.1-40 M did not alter ROS production in cells exposed to normal glucose, relatively low ('physiological' UCB concentrations (0.1-5 M attenuated ROS generation in both cell lines exposed to high glucose levels. Most strikingly, higher UCB concentrations (20-40 M increased ROS generation in bEnd3 cells exposed to high glucose, but not in similarly treated MS1 cells. These results may be of critical importance for understanding the vulnerability of the BBB endothelium upon exposure to increasing UCB levels under hyperglycemic conditions.

  16. Notch signaling: a novel regulating differentiation mechanism of human umbilical cord blood-derived mesenchymal stem cells into insulin-producing cells in vitro

    Institute of Scientific and Technical Information of China (English)

    HU Yan-hua; WU De-quan; GAO Feng; LI Guo-dong; ZHANG Xin-chen

    2010-01-01

    Background Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) could be induced to differentiate into insulin producing cells (IPCs) in vitro, which have good application potential in the cell replacement treatment of type-1 diabetes. However, the mechanisms regulating this differentiation have remained largely unknown. Notch signaling is critical in cell differentiation. This study investigated whether Notch signaling could regulate the IPCs differentiation of human UCB-MSCs. Methods Using an interfering Notch signaling protocol in vitro, we studied the role of Notch signaling in differentiation of human UCB-MSCs into IPCs. In a control group the induction took place without interfering Notch signaling. Results Human UCB-MSCs expressed the genes of Notch receptors (Notch 1 and Notch 2) and ligands (Jagged 1 and Deltalike 1). Human UCB-MSCs with over-expressing Notch signaling in differentiation resulted in the down-regulation of insulin gene level, proinsulin protein expression, and insulin-positive cells percentage compared with the control group. These results showed that over-expressing Notch signaling inhibited IPCs differentiation. Conversely, when Notch signaling was attenuated by receptor inhibitor, the induced cells increased on average by 3.06-fold (n=4, P<0.001) in insulin gene level, 2.60-fold (n=3, P <0.02) in proinsulin protein expression, and 1.62-fold (n=6, P <0.001) in the rate of IPCs compared with the control group. Notch signaling inhibition significantly promoted IPCs differentiation with about 40% of human UCB-MSCs that converted to IPCs, but these IPCs were not responsive to glucose challenge very well both in vitro and in vivo. Hence, further research has to be carried out in the future. Conclusions Notch signaling may be an important mechanism regulating IPCs differentiation of human UCB-MSCs in vitro and Notch signaling inhibition may be an efficient way to increase the number of IPCs, which may resolve the shortage of

  17. Effect of storage levels of nitric oxide derivatives in blood components [v1; ref status: indexed, http://f1000r.es/WDkFtz

    Directory of Open Access Journals (Sweden)

    Melissa A Qazi

    2012-10-01

    Full Text Available Background: Potential deleterious effects of red blood cell (RBC transfusions, especially from blood kept at length, have been ascribed to biochemical changes during storage, including those of nitric oxide (NO metabolism. Study methods and design: In this study, NO metabolites, nitrite and nitrate, were quantified in RBCs and whole blood with time of storage. Whole blood (WB, leukoreduced (LR, and non-leukoreduced (NLR components were obtained from healthy volunteer donors and stored in polyvinyl chloride bags for 42 days. Nitrite and nitrate were measured using reductive gas-phase chemiluminescence. Results: Nitrite concentrations initially decreased rapidly from about 150nmol/L, but stabilized at about 44nmol/L in room air for up to 42 days. Nitrate concentrations remained stable during storage at about 35µmol/L. Cells from bags maintained in an argon chamber showed decreased nitrite levels compared to those maintained in room air. Inhibition of enzymes implicated in the NO cycle did not alter nitrite levels. Conclusion: As erythrocytes may contribute to the control of blood flow and oxygen delivery through reduction of nitrite to NO under hypoxic conditions, the present findings provide insight into possible effects of blood transfusion. These measurements may explain some adverse effects of RBC transfusion and suggest ways of optimizing the preservation of stored blood.

  18. Resident microglia, rather than blood-derived macrophages, contribute to the earlier and more pronounced inflammatory reaction in the immature compared with the adult hippocampus after hypoxia-ischemia.

    Science.gov (United States)

    Umekawa, Takashi; Osman, Ahmed M; Han, Wei; Ikeda, Tomoaki; Blomgren, Klas

    2015-12-01

    The mechanisms of neuronal injury after hypoxia-ischemia (HI) are different in the immature and the adult brain, but microglia activation has not been compared. The purpose of this study was to phenotype resident microglia and blood-derived macrophages in the hippocampus after HI in neonatal (postnatal day 9, P9) or adult (3 months of age, 3mo) mice. Unilateral brain injury after HI was induced in Cx3cr1(GFP/+) Ccr2(RFP/+) male mice on P9 (n = 34) or at 3mo (n = 53) using the Vannucci model. Resident microglia (Cx3cr1-GFP+) proliferated and were activated earlier after HI in the P9 (1-3 days) than that in the 3mo hippocampus, but remained longer in the adult brain (3-7 days). Blood-derived macrophages (Ccr2-RFP+) peaked 3 days after HI in both immature (P9) and adult (3mo) hippocampi but were twice as frequent in adult brains, 41% vs. 21% of all microglia/macrophages. CCL2 expression was three times higher in the P9 hippocampi, indicating that the proinflammatory response was more pronounced in the immature brain after HI. This corresponded well with the higher numbers of galectin-3-positive resident microglia in the P9 hippocampi, but did not correlate with CD16/32- or CD206-positive resident microglia or blood-derived macrophages. In conclusion, resident microglia, rather than infiltrating blood-derived macrophages, proliferate and are activated earlier in the immature than in the adult brain, but remain increased longer in the adult brain. The inflammatory response is more pronounced in the immature brain, and this correlate well with galectin-3 expression in resident microglia.

  19. Angiogenesis and vasculogenesis: inducing the growth of new blood vessels and wound healing by stimulation of bone marrow-derived progenitor cell mobilization and homing.

    Science.gov (United States)

    Velazquez, Omaida C

    2007-06-01

    During embryonic development, the vasculature is among the first organs to form and is in charge of maintaining metabolic homeostasis by supplying oxygen and nutrients and removing waste products. As one would expect, blood vessels are critical not only for organ growth in the embryo but also for repair of wounded tissue in the adult. An imbalance in angiogenesis (a time-honored term that globally refers to the growth of new blood vessels) contributes to the pathogenesis of numerous malignant, inflammatory, ischemic, infectious, immune, and wound-healing disorders. This review focuses on the central role of the growth of new blood vessels in ischemic and diabetic wound healing and defines the most current nomenclature that describes the neovascularization process in wounds. There are now two well-defined, distinct, yet interrelated processes for the formation of postnatal new blood vessels, angiogenesis, and vasculogenesis. Reviewed are recent new data on vasculogenesis that promise to advance the field of wound healing.

  20. In vivo differentiation of human amniotic epithelial cells into cardiomyocyte-like cells and cell transplantation effect on myocardial infarction in rats: comparison with cord blood and adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Fang, Cheng-Hu; Jin, Jiyong; Joe, Jun-Ho; Song, Yi-Sun; So, Byung-Im; Lim, Sang Moo; Cheon, Gi Jeong; Woo, Sang-Keun; Ra, Jeong-Chan; Lee, Young-Yiul; Kim, Kyung-Soo

    2012-01-01

    Human amniotic epithelial cells (h-AECs), which have various merits as a cell source for cell therapy, are known to differentiate into cardiomyocytes in vitro. However, the ability of h-AECs to differentiate into cardiomyocytes in vivo and their cell transplantation effects on myocardial infarction are still unknown. In this study, we assessed whether h-AECs could differentiate into cardiomyocytes in vivo and whether h-AECs transplantation can decrease infarct size and improve cardiac function, in comparison to transplantation of cord blood-derived mesenchymal stem cells (MSCs) or adipose tissue-derived MSCs. For our study, we injected h-AECs, cord blood-derived MSCs, adipose tissue-derived MSCs, and saline into areas of myocardial infarction in athymic nude rats. After 4 weeks, 3% of the surviving h-AECs expressed myosin heavy chain, a marker specific to the myocardium. Compared with the saline group, all cell-implanted groups showed a higher ejection fraction, lower infarct area by positron emission tomography and histology, and more abundant myocardial gene and protein expression in the infarct area. We showed that h-AECs can differentiate into cardiomyocyte-like cells, decrease infarct size, and improve cardiac function in vivo. The beneficial effects of h-AECs were comparable to those of cord blood and adipose tissue-derived MSCs. These results support the need for further studies of h-AECs as a cell source for myocardial regeneration due to their plentiful availability, low immunity, and lack of ethical issues related to their use.

  1. Mutation of the NPM1 gene contributes to the development of donor cell-derived acute myeloid leukemia after unrelated cord blood transplantation for acute lymphoblastic leukemia.

    Science.gov (United States)

    Rodríguez-Macías, Gabriela; Martínez-Laperche, Carolina; Gayoso, Jorge; Noriega, Víctor; Serrano, David; Balsalobre, Pascual; Muñoz-Martínez, Cristina; Díez-Martín, José L; Buño, Ismael

    2013-08-01

    Donor cell leukemia (DCL) is a rare but severe complication after allogeneic stem cell transplantation. Its true incidence is unknown because of a lack of correct recognition and reporting, although improvements in molecular analysis of donor-host chimerism are contributing to a better diagnosis of this complication. The mechanisms of leukemogenesis are unclear, and multiple factors can contribute to the development of DCL. In recent years, cord blood has emerged as an alternative source of hematopoietic progenitor cells, and at least 12 cases of DCL have been reported after unrelated cord blood transplantation. We report a new case of DCL after unrelated cord blood transplantation in a 44-year-old woman diagnosed as having acute lymphoblastic leukemia with t(1;19) that developed acute myeloid leukemia with normal karyotype and nucleophosmin (NPM1) mutation in donor cells. To our knowledge, this is the first report of NPM1 mutation contributing to DCL development.

  2. Function, expression and localization of annexin A7 in platelets and red blood cells: Insights derived from an annexin A7 mutant mouse

    Directory of Open Access Journals (Sweden)

    Zamparelli Carlotta

    2003-08-01

    Full Text Available Abstract Background Annexin A7 is a Ca2+- and phospholipid-binding protein expressed as a 47 and 51 kDa isoform, which is thought to be involved in membrane fusion processes. Recently the 47 kDa isoform has been identified in erythrocytes where it was proposed to be a key component in the process of the Ca2+-dependent vesicle release, a process with which red blood cells might protect themselves against an attack by for example complement components. Results The role of annexin A7 in red blood cells was addressed in erythrocytes from anxA7-/- mice. Interestingly, the Ca2+-mediated vesiculation process was not impaired. Also, the membrane organization appeared not to be disturbed as assessed using gradient fractionation studies. Instead, lack of annexin A7 led to an altered cell shape and increased osmotic resistance of red blood cells. Annexin A7 was also identified in platelets. In these cells its loss led to a slightly slower aggregation velocity which seems to be compensated by an increased number of platelets. The results appear to rule out an important role of annexin A7 in membrane fusion processes occurring in red blood cells. Instead the protein might be involved in the organization of the membrane cytoskeleton. Red blood cells may represent an appropriate model to study the role of annexin A7 in cellular processes. Conclusion We have demonstrated the presence of both annexin A7 isoforms in red blood cells and the presence of the small isoform in platelets. In both cell types the loss of annexin A7 impairs cellular functions. The defects observed are however not compatible with a crucial role for annexin A7 in membrane fusion processes in these cell types.

  3. Blood smear

    Science.gov (United States)

    ... some red blood cells shaped like spheres ( hereditary spherocytosis ) Increased breakdown of RBCs Presence of RBCs with ... normal Red blood cells, elliptocytosis Red blood cells, spherocytosis Acute lymphocytic leukemia - photomicrograph Red blood cells, multiple ...

  4. Blood culture

    Science.gov (United States)

    Culture - blood ... A blood sample is needed . The site where blood will be drawn is first cleaned with an antiseptic such ... organism from the skin getting into (contaminating) the blood sample and causing a false-positive result (see ...

  5. Blood Thinners

    Science.gov (United States)

    If you have some kinds of heart or blood vessel disease, or if you have poor blood flow to your brain, your doctor may recommend that you take a blood thinner. Blood thinners reduce the risk of heart ...

  6. Blood transfusions

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000431.htm Blood transfusions To use the sharing features on this ... several sources of blood which are described below. Blood From the Public (Volunteer Blood Donation) The most ...

  7. Associated factors for higher lead and cadmium blood levels, and reference values derived from general population of São Paulo, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Kira, Carmen Silvia, E-mail: carmkira@ial.sp.gov.br [Instituto Adolfo Lutz, Centro de Materiais de Referência, Av. Dr. Arnaldo, 355, São Paulo, SP CEP 01246-000 (Brazil); Sakuma, Alice Momoyo [Instituto Adolfo Lutz, Centro de Materiais de Referência, Av. Dr. Arnaldo, 355, São Paulo, SP CEP 01246-000 (Brazil); De Capitani, Eduardo Mello [Universidade Estadual de Campinas — UNICAMP, Faculdade de Ciências Médicas, Departamento de Clínica Médica, Centro de Controle de Intoxicações (Brazil); Umbelino de Freitas, Clarice [Secretaria de Estado da Saúde/SP, Coordenadoria de Controle de Doenças (Brazil); Cardoso, Maria Regina Alves [Universidade de São Paulo, Faculdade de Saúde Pública, Departamento de Epidemiologia (Brazil); Gouveia, Nelson [Universidade de São Paulo — USP, Faculdade de Medicina, Departamento de Medicina Preventiva (Brazil)

    2016-02-01

    Human activities are associated with emissions of various metals into the environment, among which the heavy metals lead and cadmium stand out, as they pose a risk to human life even at low concentrations. Thus, accurate knowledge of the levels of these metals exhibited by the overall population, including children, is important. The aim of this study was to estimate the concentrations of lead and cadmium in the blood of adults, adolescents and children residing in the city of São Paulo, assess factors associated with higher lead and cadmium blood levels, and to establish reference values for this population. The study sample consisted of 669 adults over 20 years old, 264 adolescents aged 12 to 19 years old and 391 children under 11 years old from both genders. The samples were collected at the end of 2007 and during 2008 in different city zones. Higher blood lead concentration was significantly associated with gender, smoking, offal intake, area of residence and age. The blood cadmium concentration was significantly associated with gender, smoking, consumption of distilled beverages and age. The reference values of lead and cadmium established for adults above 20 years old were 33 μg/L and 0.6 μg/L, respectively, for adolescents (12 to 19 years old) were 31 μg/L and 0.6 μg/L, respectively and for children under 11 years old were 29 μg/L and 0.2 μg/L, respectively. The results of this study indicate that the exposure levels of the investigated population to lead and cadmium are low. - Highlights: • The exposure of population of São Paulo city to lead and cadmium is low. • Pb level was associated with gender, smoking, offal intake, area of residence, age. • Cd level was associated with gender, smoking, distilled beverages, age. • RV for Pb in blood for children and adolescents were 29 and 31 μg/L, respectively. • RV for Cd in blood for children and adolescents were 0.2 and 0.6 μg/L, respectively.

  8. Paracrine proangiopoietic effects of human umbilical cord blood-derived purified CD133+ cells--implications for stem cell therapies in regenerative medicine.

    Science.gov (United States)

    Ratajczak, Janina; Kucia, Magda; Mierzejewska, Kasia; Marlicz, Wojciech; Pietrzkowski, Zbigniew; Wojakowski, Wojciech; Greco, Nicholas J; Tendera, Michal; Ratajczak, Mariusz Z

    2013-02-01

    CD133+ cells purified from hematopoietic tissues are enriched mostly for hematopoietic stem/progenitor cells, but also contain some endothelial progenitor cells and very small embryonic-like stem cells. CD133+ cells, which are akin to CD34+ cells, are a potential source of stem cells in regenerative medicine. However, the lack of convincing donor-derived chimerism in the damaged organs of patients treated with these cells suggests that the improvement in function involves mechanisms other than a direct contribution to the damaged tissues. We hypothesized that CD133+ cells secrete several paracrine factors that play a major role in the positive effects observed after treatment and tested supernatants derived from these cells for the presence of such factors. We observed that CD133+ cells and CD133+ cell-derived microvesicles (MVs) express mRNAs for several antiapoptotic and proangiopoietic factors, including kit ligand, insulin growth factor-1, vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8. These factors were also detected in a CD133+ cell-derived conditioned medium (CM). More important, the CD133+ cell-derived CM and MVs chemoattracted endothelial cells and display proangiopoietic activity both in vitro and in vivo assays. This observation should be taken into consideration when evaluating clinical outcomes from purified CD133+ cell therapies in regenerative medicine.

  9. Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer

    DEFF Research Database (Denmark)

    Idorn, Manja; Køllgaard, Tania; Kongsted, Per

    2014-01-01

    and function of immune suppressive cell subsets in the peripheral blood of 41 patients with prostate cancer (PC) and 36 healthy donors (HD) showed a significant increase in circulating CD14(+) HLA-DR(low/neg) monocytic MDSC (M-MDSC) and Tregs in patients with PC compared to HD. Furthermore, M-MDSC frequencies...... and other cell types may suggest ways to tackle their induction and/or function to improve immunological tumor control....

  10. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy.

    Science.gov (United States)

    Potdar, Pd; Subedi, Rp

    2011-01-01

    Acute Lymphocytic Leukemia (ALL) is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem cells from peripheral blood of ALL patients, which will be further characterized for their normal phenotypes by using specific molecular stem cell markers. This is the first study, which defines the existing phenotypes of isolated MSCs and HSCs from peripheral blood of ALL patients. We have established three cell lines in which two were Mesenchymal stem cells designated as MSCALL and MSCnsALL and one was suspension cell line designated as HSCALL. The HSCALL cell line was developed from the lymphocyte like cells secreted by MSCALL cells. Our study also showed that MSCALL from peripheral blood of ALL patient secreted hematopoietic stem cells in vitro culture. We have characterized all three-cell lines by 14 specific stem cell molecular markers. It was found that both MSC cell lines expressed CD105, CD13, and CD73 with mixed expression of CD34 and CD45 at early passage whereas, HSCALL cell line expressed prominent feature of hematopoietic stem cells such as CD34 and CD45 with mild expression of CD105 and CD13. All three-cell lines expressed LIF, OCT4, NANOG, SOX2, IL6, and DAPK. These cells mildly expressed COX2 and did not express BCR-ABL. Overall it was shown that isolated MSCs and HSCs can be use as a model system to study the mechanism of leukemia at stem cell level and their use in stem cell regeneration therapy for Acute Lymphocytic Leukemia.

  11. Preliminary evaluation of treatment efficacy of umbilical cord blood-derived mesenchymal stem cell-differentiated cardiac pro-genitor cells in a myocardial injury mouse model

    Directory of Open Access Journals (Sweden)

    Truc Le-Buu Pham

    2015-12-01

    Full Text Available Recently, stem cell therapy has been investigated as a strategy to prevent or reverse damage to heart tissue. Although the results of cell transplantation in animal models and patients with myocardial ischemia are promising, the selection of the appropriate cell type remains an issue that requires consideration. In this study, we aimed to evaluate the effect of cardiac progenitor cell transplantation in a mouse model of myocardial ischemia. The cardiac progenitor cells used for transplantation were differentiated from umbilical cord blood mesenchymal stem cells. Animal models injected with phosphate-buffered saline (PBS and healthy mice were used as controls. Cell grafting was assessed by changes in blood pressure and histological evaluation. After 14 days of transplantation, the results demonstrated that the blood pressure of transplanted mice was stable, similar to healthy mice, whereas it fluctuated in PBS-injected mice. Histological analysis showed that heart tissue had regenerated in transplanted mice, but remained damaged in PBS-injected mice. Furthermore, trichrome staining revealed that the transplanted mice did not generate significant amount of scar tissue compared with PBS-injected control mice. In addition, the cardiac progenitor cells managed to survive and integrate with local cells in cell-injected heart tissue 14 days after transplantation. Most importantly, the transplanted cells did not exhibit tumorigenesis. In conclusion, cardiac progenitor cell transplantation produced a positive effect in a mouse model of myocardial ischemia. [Biomed Res Ther 2015; 2(12.000: 435-445

  12. Whole transcriptome RNA sequencing data from blood leukocytes derived from Parkinson's disease patients prior to and following deep brain stimulation treatment

    Directory of Open Access Journals (Sweden)

    Lilach Soreq

    2015-03-01

    Full Text Available Recent evidence demonstrates the power of RNA sequencing (RNA-Seq for identifying valuable and urgently needed blood biomarkers and advancing both early and accurate detection of neurological diseases, and in particular Parkinson's disease (PD. RNA sequencing technology enables non-biased, high throughput, probe-independent inspection of expression data and high coverage and both quantification of global transcript levels as well as the detection of expressed exons and junctions given a sufficient sequencing depth (coverage. However, the analysis of sequencing data frequently presents a bottleneck. Tools for quantification of alternative splicing from sequenced libraries hardly exist at the present time, and methods that support multiple sequencing platforms are especially lacking. Here, we describe in details a whole RNA-Seq transcriptome dataset produced from PD patient's blood leukocytes. The samples were taken prior to, and following deep brain stimulation (DBS treatment while being on stimulation and following 1 h of complete electrical stimulation cessation and from healthy control volunteers. We describe in detail the methodology applied for analyzing the RNA-Seq data including differential expression of long noncoding RNAs (lncRNAs. We also provide details of the corresponding analysis of in-depth splice isoform data from junction and exon reads, with the use of the software AltAnalyze. Both the RNA-Seq raw (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42608 and analyzed data (https://www.synapse.org/#!Synapse:syn2805267 may be found valuable towards detection of novel blood biomarkers for PD.

  13. Non-dipping blood pressure variations in adult Kazakhs are derived from decreased daytime physical activity and increased nighttime sympathetic activity.

    Science.gov (United States)

    Kawamura, Hiroshi; Ozawa, Yukio; Izumi, Yoichi; Kasamaki, Yuji; Nakayama, Tomohiro; Mitsubayashi, Hiromi; Ohta, Masakatsu; Ichimaru, Yuhei

    2016-01-01

    Many of the elderly Kazakhs have been found to exhibit non-dipping blood pressure variations (BPV). Such variations are seen in both normotensive and hypertensive Kazakhs. The purpose of this study was (1) to determine whether middle-aged Kazakhs also include large numbers of non-dippers, (2) to compare the characteristics of non-dipping and dipping, and (3) to clarify the mechanisms responsible for non-dipping type BPV by examining the autonomic nervous activity and physical activity. We performed ambulatory blood pressure (BP) monitoring. The subjects were divided into two groups (dipping and non-dipping type). We monitored the subjects' physical activity with accelerometry and assessed their autonomic nerve activity by performing a frequency domain analysis of their heart rate variability (HRV). The power spectral density (PSD) of the HRV was calculated using fast Fourier transformation. We analyzed the systolic blood pressure (SBP) variations with the maximum entropy method (MEM). The dippers and non-dippers accounted for 48% and 52% of the subjects, respectively. MEM analysis revealed that the SBP variations of the non-dippers exhibited a 24 hour periodicity with a very weak PSD as well as an ultradian periodicity. The non-dippers exhibited higher low-frequency/high-frequency (LF/HF) ratio and lower HF/(LF + HF) ratios than the dippers, particularly during the nighttime. In addition, the non-dippers performed less physical activity than the dippers. These differences in cardiac autonomic function and physical activity might contribute to the generation of a weak circadian rhythm in SBP, and thus, ultimately lead to the non-dipping SBP variations observed in non-dipper Kazakhs.

  14. Diagnostic examination performance by using microvascular leakage, cerebral blood volume, and blood flow derived from 3-T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in the differentiation of glioblastoma multiforme and brain metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Server, Andres; Nakstad, Per H. [Oslo University Hospital-Ullevaal, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Oslo (Norway); Orheim, Tone E.D. [Oslo University Hospital, Interventional Centre, Oslo (Norway); Graff, Bjoern A. [Oslo University Hospital-Ullevaal, Department of Radiology and Nuclear Medicine, Oslo (Norway); Josefsen, Roger [Oslo University Hospital-Ullevaal, Department of Neurosurgery, Oslo (Norway); Kumar, Theresa [Oslo University Hospital-Ullevaal, Department of Pathology, Oslo (Norway)

    2011-05-15

    Conventional magnetic resonance (MR) imaging has limited capacity to differentiate between glioblastoma multiforme (GBM) and metastasis. The purposes of this study were: (1) to compare microvascular leakage (MVL), cerebral blood volume (CBV), and blood flow (CBF) in the distinction of metastasis from GBM using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MRI), and (2) to estimate the diagnostic accuracy of perfusion and permeability MR imaging. A prospective study of 61 patients (40 GBMs and 21 metastases) was performed at 3 T using DSC-MRI. Normalized rCBV and rCBF from tumoral (rCBVt, rCBFt), peri-enhancing region (rCBVe, rCBFe), and by dividing the value in the tumor by the value in the peri-enhancing region (rCBVt/e, rCBFt/e), as well as MVL were calculated. Hemodynamic and histopathologic variables were analyzed statistically and Spearman/Pearson correlations. Receiver operating characteristic curve analysis was performed for each of the variables. The rCBVe, rCBFe, and MVL were significantly greater in GBMs compared with those of metastases. The optimal cutoff value for differentiating GBM from metastasis was 0.80 which implies a sensitivity of 95%, a specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 97% for rCBVe ratio. We found a modest correlation between rCBVt and rCBFt ratios. MVL measurements in GBMs are significantly higher than those in metastases. Statistically, both rCBVe, rCBVt/e and rCBFe, rCBFt/e were useful in differentiating between GBMs and metastases, supporting the hypothesis that perfusion MR imaging can detect infiltration of tumor cells in the peri-enhancing region. (orig.)

  15. Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161(+)Th1 Cells) to CD161(+)Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients.

    Science.gov (United States)

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161(+)Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.

  16. β-Globin sleeping beauty transposon reduces red blood cell sickling in a patient-derived CD34(+)-based in vitro model.

    Science.gov (United States)

    Sjeklocha, Lucas M; Wong, Phillip Y-P; Belcher, John D; Vercellotti, Gregory M; Steer, Clifford J

    2013-01-01

    The ultimate goal of gene therapy for sickle cell anemia (SCA) is an improved phenotype for the patient. In this study, we utilized bone marrow from a sickle cell patient as a model of disease in an in vitro setting for the hyperactive Sleeping Beauty transposon gene therapy system. We demonstrated that mature sickle red blood cells containing hemoglobin-S and sickling in response to metabisulfite can be generated in vitro from SCA bone marrow. These cells showed the characteristic morphology and kinetics of hemoglobin-S polymerization, which we quantified using video microscopy and imaging cytometry. Using video assessment, we showed that delivery of an IHK-β(T87Q) antisickling globin gene by Sleeping Beauty via nucleofection improves metrics of sickling, decreasing percent sickled from 53.2 ± 2.2% to 43.9 ± 2.0%, increasing the median time to sickling from 8.5 to 9.6 min and decreasing the maximum rate of sickling from 2.3 x 10(-3) sickling cells/total cells/sec in controls to 1.26 x 10(-3) sickling cells/total cells/sec in the IHK-β(T87Q)-globin group (p cells decreased from 34.8 ± 4.5% to 29.5 ± 3.0% in control versus treated (p red blood cells in vitro.

  17. Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis.

    Science.gov (United States)

    Takeda, Takashi; Banno, Kouji; Yanokura, Megumi; Adachi, Masataka; Iijima, Moito; Kunitomi, Haruko; Nakamura, Kanako; Iida, Miho; Nogami, Yuya; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Yamagami, Wataru; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke

    2016-10-14

    Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%)-1 out of 58 (1.72%) with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.

  18. Lethal effect of mononuclear cells derived from human umbilical cord blood differentiating into dendritic cells after in vitro induction of cytokines on neuroblastoma cells

    Institute of Scientific and Technical Information of China (English)

    Zhenghai Qu; Jianxin Zuo; Lirong Sun; Xindong Qu

    2006-01-01

    BACKGROUND: Dendritic cell is the most major antigen presenting cell of organism. It is proved in recent studies that human umbilical cord blood mononuclear cells induced and cultured in vitro by recombinant human granuIocyte-macrophage colony stimulating factor (rhG-MCSF) and recombinant human interleukin-4 (rhlL-4) can generate a great many dendritic cells and promote the lethal effect of T cells on human neuroblastoma, but it is unclear that whether the lethal effect is associated with the most proper concentration of dendritic cells.OBJ ECTIVE: To investigate the lethal effect of human umbilical cord blood mononuclear cells induced in vitro by cytokines differentiating into dendritic cells on human neuroblastoma, and its best concentration range.DESIGN: Open experiment.SETTING: Department of Pediatrics, the Medical School Hospital of Qingdao University.MATERIALS: The study was carried out in the Shandong Provincial Key Laboratory (Laboratory for the Department of Pediatrics of the Medical School Hospital of Qingdao University) during September 2005 to May 2006.Human umbilical cord blood samples were taken from the healthy newborn infants of full-term normal delivery during October to November 2005 in the Medical School Hospital of Qingdao University, and were voluntarily donated by the puerperas. Main instruments: type 3111 CO2 incubator (Forma Scientific, USA), type 550 ELISA Reader (Bio-Rad, USA). Main reagents: neuroblastoma cell line SK-N-SH (Shanghai Institute of Life Science, Chinese Academy of Sciences), RPMI-1640 culture fluid and fetal bovine serum (Hyclone), rhlL-4 (Promega, USA), rhG-MCSF (Harbin Pharmaceutic Group Bioengineering Co. Ltd), rat anti-human CD1a monoclonal antibody and FITC-labeled rabbit anti-rat IgG (Xiehe Stem cell Gene Engineering Co. Ltd).METHODS: ① Human umbilical cord blood mononuclear cells obtained with attachment methods differentiated into human umbilical cord blood dendritic cells, presenting typical morphology of

  19. Blood Donation

    Science.gov (United States)

    Tests and Procedures Blood donation By Mayo Clinic Staff Blood donation is a voluntary procedure. You agree to have blood drawn so that it can ... have a disease that requires blood components. Blood donation makes all of this possible. There are several ...

  20. Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women.

    Science.gov (United States)

    Unternaehrer, Eva; Meyer, Andrea Hans; Burkhardt, Susan C A; Dempster, Emma; Staehli, Simon; Theill, Nathan; Lieb, Roselind; Meinlschmidt, Gunther

    2015-01-01

    In adults, reporting low and high maternal care in childhood, we compared DNA methylation in two stress-associated genes (two target sequences in the oxytocin receptor gene, OXTR; one in the brain-derived neurotrophic factor gene, BDNF) in peripheral whole blood, in a cross-sectional study (University of Basel, Switzerland) during 2007-2008. We recruited 89 participants scoring  33 (n = 42, 35 women) on the maternal care subscale of the Parental Bonding Instrument (PBI) at a previous assessment of a larger group (N = 709, range PBI maternal care = 0-36, age range = 19-66 years; median 24 years). 85 participants gave blood for DNA methylation analyses (Sequenom(R) EpiTYPER, San Diego, CA) and cell count (Sysmex PocH-100i™, Kobe, Japan). Mixed model statistical analysis showed greater DNA methylation in the low versus high maternal care group, in the BDNF target sequence [Likelihood-Ratio (1) = 4.47; p = 0.035] and in one OXTR target sequence Likelihood-Ratio (1) = 4.33; p = 0.037], but not the second OXTR target sequence [Likelihood-Ratio (1) BDNF (estimate = -0.005, 95% CI = -0.025 to 0.015; p = 0.626) or OXTR DNA methylation (estimate = -0.015, 95% CI = -0.038 to 0.008; p = 0.192). Hence, low maternal care in childhood was associated with greater DNA methylation in an OXTR and a BDNF target sequence in blood cells in adulthood. Although the study has limitations (cross-sectional, a wide age range, only three target sequences in two genes studied, small effects, uncertain relevance of changes in blood cells to gene methylation in brain), the findings may indicate components of the epiphenotype from early life stress.

  1. β-Globin sleeping beauty transposon reduces red blood cell sickling in a patient-derived CD34(+-based in vitro model.

    Directory of Open Access Journals (Sweden)

    Lucas M Sjeklocha

    Full Text Available The ultimate goal of gene therapy for sickle cell anemia (SCA is an improved phenotype for the patient. In this study, we utilized bone marrow from a sickle cell patient as a model of disease in an in vitro setting for the hyperactive Sleeping Beauty transposon gene therapy system. We demonstrated that mature sickle red blood cells containing hemoglobin-S and sickling in response to metabisulfite can be generated in vitro from SCA bone marrow. These cells showed the characteristic morphology and kinetics of hemoglobin-S polymerization, which we quantified using video microscopy and imaging cytometry. Using video assessment, we showed that delivery of an IHK-β(T87Q antisickling globin gene by Sleeping Beauty via nucleofection improves metrics of sickling, decreasing percent sickled from 53.2 ± 2.2% to 43.9 ± 2.0%, increasing the median time to sickling from 8.5 to 9.6 min and decreasing the maximum rate of sickling from 2.3 x 10(-3 sickling cells/total cells/sec in controls to 1.26 x 10(-3 sickling cells/total cells/sec in the IHK-β(T87Q-globin group (p < 0.001. Using imaging cytometry, the percentage of elongated sickled cells decreased from 34.8 ± 4.5% to 29.5 ± 3.0% in control versus treated (p < 0.05. These results support the potential use of Sleeping Beauty as a clinical gene therapy vector and provide a useful tool for studying sickle red blood cells in vitro.

  2. Preliminary evaluation of intravenous infusion and intrapancreatic injection of human umbilical cord blood-derived mesenchymal stem cells for the treatment of diabetic mice

    Directory of Open Access Journals (Sweden)

    Ngoc Kim Phan

    2014-03-01

    Full Text Available Type 1 diabetes mellitus is characterized by the destruction of pancreatic islet beta cells, which leads to insulin insufficiency, hyperglycemia, and reduced metabolic glucose level. Insulin replacement is the current standard therapy for type 1 diabetes mellitus but has several limitations. Pancreatic islet transplantation can result in the production of exogenous insulin, but its use is limited by immune-rejection and donor availability. Recent studies have shown that mesenchymal stem cells (MSCs can transdifferentiate into insulin-producing cells (IPCs, which could be utilized for diabetes mellitus treatment. Previously published reports have demonstrated that MSC or IPC transplantation could produce significant improvement in mouse models of diabetes mellitus. This study was aimed at determining the effects of two different methods of MSC transplantation on the efficacy of diabetes mellitus treatment in mouse models. The MSCs were isolated from umbilical cord blood and were proliferated following a previously published procedure. Diabetes mellitus was induced in mice by streptozotocin (STZ injection. Thirty days after transplantation, the weight of the mice treated by intra-venous infusion and intra-pancreatic injection was found to be 22% and 14% higher than that of the un-treated mice. The blood glucose concentrations in both intra-venous infusion and intra-pancreatic injection groups decreased and remained more stable than those in the control group. Moreover, insulin was detected in the serum of the treated mice, and the pancreas also showed gradual recovery. Based on the results of this preliminary investigation, intra-venous infusion seems more suitable than intra-pancreatic injection for MSC transplantation for diabetes mellitus treatment. [Biomed Res Ther 2014; 1(3.000: 98-105

  3. Donating Blood

    Science.gov (United States)

    ... can't get an infection or disease from giving blood. The needles and other equipment used are sterile ... part of blood (plasma) within 72 hours after giving blood. It generally takes about 4–8 weeks to ...

  4. Nrf2 expression is increased in peripheral blood mononuclear cells derived from mild–moderate ex-smoker COPD patients with persistent oxidative stress

    Directory of Open Access Journals (Sweden)

    Fratta Pasini AM

    2016-07-01

    Full Text Available Anna Maria Fratta Pasini,1 Marcello Ferrari,2 Chiara Stranieri,1 Paola Vallerio,1 Chiara Mozzini,1 Ulisse Garbin,1 Giorgia Zambon,1 Luciano Cominacini1 1Department of Medicine, Section of Internal Medicine, 2Department of Medicine, Unit of Respiratory Diseases, University of Verona, Verona, Italy Abstract: Inadequacy of antioxidant nuclear factor-E2-related factor 2 (Nrf2 and endoplasmic reticulum stress-mediated unfolded protein response has been implicated in severe chronic obstructive pulmonary disease (COPD and cigarette smoking-induced emphysema. As evidence suggests that the ability to upregulate Nrf2 expression may influence the progression of COPD and no data exist up to now in ex-smokers with mild–moderate COPD, this study was first aimed to evaluate Nrf2 and unfolded protein response expression in peripheral blood mononuclear cells (PBMC of mild–moderate ex-smokers with COPD compared to smoking habit-matched non-COPD subjects. Then, we tested whether oxidative stress persists after cigarette smoking cessation and whether the concentrations of oxidized phospholipids (oxidation products of the phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine [oxPAPC] in the PBMC of the same subjects may have a causative role in determining the upregulation of Nrf2. The expression (mRNA and protein of Nrf2 and of its related gene heme oxygenase-1 was significantly increased in COPD group without differences in the unfolded protein response. Plasma malondialdehyde, the circulating marker of oxidative stress, and oxPAPC in PBMC were significantly higher in COPD than in non-COPD subjects. The fact that the expression of p47phox, a subunit of NADPH oxidase, was increased in PBMC of COPD patients and that it was directly correlated with oxPAPC may indicate that oxPAPC may be one of the determinants of oxidative stress-induced Nrf2 upregulation. Finally, we also demonstrated that lung function inversely correlated with plasma

  5. Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity.

    Science.gov (United States)

    Naito, Kei; Ueda, Yuji; Itoh, Tsuyoshi; Fuji, Nobuaki; Shimizu, Keiji; Yano, Yutaro; Yamamoto, Yoshiki; Imura, Kenichiro; Kohara, Junji; Iwamoto, Arihiro; Shiozaki, Atsushi; Tamai, Hidemasa; Shimizu, Takeshi; Mazda, Osam; Yamagishi, Hisakazu

    2006-06-01

    Dendritic cells (DCs) have been shown to be potent in inducing cytotoxic T cell (CTL) response leading to the efficient anti-tumor effect in active immunotherapy. Myeloid DCs are conventionally generated from human peripheral blood monocytes in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Streptococcal preparation OK-432, which is known to be a multiple cytokine inducer, has been extensively studied as to its maturation effects on immature DCs using an in vitro culture system. The purpose of this study was to examine whether it could be possible to generate mature DCs directly from peripheral monocytes using OK-432. We specifically focused on the possibility that recombinant cytokines, which are considered to be essential for in vitro DC generation, could be substituted by OK-432. Human peripheral monocytes, which were obtained from patients with advanced cancer, were cultured with IL-4 and OK-432 for 7 days. Cultured cells were compared with DCs generated in the presence of IL-4 and GM-CSF with or without OK-432 with regard to the surface phenotype as well as the antigen-presenting capacity. As a result, the culture of monocytes in the presence of IL-4 followed by the addition of OK-432 on day 4 (IL-4/OK-DC) induced cells with a fully mature DC phenotype. Functional assays also demonstrated that IL-4/OK-DCs had a strong antigen-presenting capacity determined by their enhanced antigen-specific CTL response and exerted a Th1-type T cell response which is critical for the induction of anti-tumor response. In conclusion, human peripheral blood monocytes cultured in the presence of IL-4 and OK-432 without exogenous GM-CSF demonstrated a fully mature DC phenotype and strong antigen-presenting capacity. This one-step culture protocol allows us to generate fully mature DCs directly from monocytes in 7 days and thus, this protocol can be applicable for DC-based anti-tumor immunotherapy.

  6. Cytotoxic activity against human neuroblastoma and melanoma cells mediated by IgM antibodies derived from peripheral blood of healthy donors.

    Science.gov (United States)

    Devarapu, Satish Kumar; Mamidi, Srinivas; Plöger, Frank; Dill, Othmar; Blixt, Ola; Kirschfink, Michael; Schwartz-Albiez, Reinhard

    2016-06-15

    A small percentage of healthy donors identified in the Western population carry antibodies in their peripheral blood which convey cytotoxic activity against certain human melanoma and neuroblastoma cell lines. We measured the cytotoxic activity of sera and plasmas from healthy donors on the human neuroblastoma cell line Kelly and various melanoma cell lines. Antibodies of IgM isotype, presumably belonging to the class of naturally occurring antibodies, exerted cytotoxic activity in a complement-dependent fashion. Apart from complement-dependent tumor cell lysis, we observed C3 opsonization in all tumor cell lines upon treatment with cytotoxic plasmas. Cell lines tested primarily expressed membrane complement regulatory proteins (mCRP) CD46, CD55 and CD59 to various extents. Blocking of mCRPs by monoclonal antibodies enhanced cell lysis and opsonization, though some melanoma cells remained resistant to complement attack. Epitopes recognized by cytotoxic antibodies were represented by gangliosides such as GD2 and GD3, as evidenced by cellular sialidase pretreatment and enhanced expression of distinct gangliosides. It remains to be clarified why only a small fraction of healthy persons carry these antitumor cytotoxic antibodies.

  7. Circulating brain derived neurotrophic factor (BDNF) and frequency of BDNF positive T cells in peripheral blood in human ischemic stroke: Effect on outcome.

    Science.gov (United States)

    Chan, Adeline; Yan, Jun; Csurhes, Peter; Greer, Judith; McCombe, Pamela

    2015-09-15

    The aim of this study was to measure the levels of circulating BDNF and the frequency of BDNF-producing T cells after acute ischaemic stroke. Serum BDNF levels were measured by ELISA. Flow cytometry was used to enumerate peripheral blood leukocytes that were labelled with antibodies against markers of T cells, T regulatory cells (Tregs), and intracellular BDNF. There was a slight increase in serum BDNF levels after stroke. There was no overall difference between stroke patients and controls in the frequency of CD4(+) and CD8(+) BDNF(+) cells, although a subgroup of stroke patients showed high frequencies of these cells. However, there was an increase in the percentage of BDNF(+) Treg cells in the CD4(+) population in stroke patients compared to controls. Patients with high percentages of CD4(+) BDNF(+) Treg cells had a better outcome at 6months than those with lower levels. These groups did not differ in age, gender or initial stroke severity. Enhancement of BDNF production after stroke could be a useful means of improving neuroprotection and recovery after stroke.

  8. Glycogenolysis in astrocytes supports blood-borne glucose channeling not glycogen-derived lactate shuttling to neurons: evidence from mathematical modeling.

    Science.gov (United States)

    DiNuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

    2010-12-01

    In this article, we examined theoretically the role of human cerebral glycogen in buffering the metabolic requirement of a 360-second brain stimulation, expanding our previous modeling study of neurometabolic coupling. We found that glycogen synthesis and degradation affects the relative amount of glucose taken up by neurons versus astrocytes. Under conditions of 175:115 mmol/L (∼1.5:1) neuronal versus astrocytic activation-induced Na(+) influx ratio, ∼12% of astrocytic glycogen is mobilized. This results in the rapid increase of intracellular glucose-6-phosphate level on stimulation and nearly 40% mean decrease of glucose flow through hexokinase (HK) in astrocytes via product inhibition. The suppression of astrocytic glucose phosphorylation, in turn, favors the channeling of glucose from interstitium to nearby activated neurons, without a critical effect on the concurrent intercellular lactate trafficking. Under conditions of increased neuronal versus astrocytic activation-induced Na(+) influx ratio to 190:65 mmol/L (∼3:1), glycogen is not significantly degraded and blood glucose is primarily taken up by neurons. These results support a role for astrocytic glycogen in preserving extracellular glucose for neuronal utilization, rather than providing lactate to neurons as is commonly accepted by the current 'thinking paradigm'. This might be critical in subcellular domains during functional conditions associated with fast energetic demands.

  9. Controlled study on the effect of pentoxifylline and an ergot alkaloid derivative on regional cerebral blood flow in patients with chronic cerebrovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, A.; Tsuda, Y.

    1988-05-01

    Regional cerebral blood flow (rCBF) in 90 patients with CBF decreased due to vascular diseases was studied by using the xenon 133 inhalation technique and a 32-detector setup. Whereas 30 patients received their standard basic therapy only and were regarded as controls, 30 others received 3 x 2 mg/day of an ergot alkaloid (co-dergocrine mesylate), and 30 others received 3 x 400 mg pentoxifylline (slow-release formulation)/day orally. Therapy was performed for eight weeks and CBF measured before start of treatment, after a four-week treatment period, and at the end of the study. CBF did not change significantly in the control group; both the pentoxifylline and the ergot alkaloid group presented with a significant increase in the CBF. This positive effect was significantly more pronounced in the pentoxifylline group and affected more ischemic than other brain tissues. In addition, symptoms like sleep disturbances, vertigo, and tinnitus improved significantly during the pentoxifylline observation period.

  10. Matrix metalloproteinase-9 and stromal cell-derived factor-1 act synergistically to support migration of blood-borne monocytes into the injured spinal cord.

    Science.gov (United States)

    Zhang, Haoqian; Trivedi, Alpa; Lee, Jung-Uek; Lohela, Marja; Lee, Sang Mi; Fandel, Thomas M; Werb, Zena; Noble-Haeusslein, Linda J

    2011-11-01

    The infiltration of monocytes into the lesioned site is a key event in the inflammatory response after spinal cord injury (SCI). We hypothesized that the molecular events governing the infiltration of monocytes into the injured cord involve cooperativity between the upregulation of the chemoattractant stromal cell-derived factor-1 (SDF-1)/CXCL12 in the injured cord and matrix metalloproteinase-9 (MMP-9/gelatinase B), expressed by infiltrating monocytes. SDF-1 and its receptor CXCR4 mRNAs were upregulated in the injured cord, while macrophages immunoexpressed CXCR4. When mice, transplanted with bone marrow cells from green fluorescent protein (GFP) transgenic mice, were subjected to SCI, GFP+ monocytes infiltrated the cord and displayed gelatinolytic activity. In vitro studies confirmed that SDF-1α, acting through CXCR4, expressed on bone marrow-derived macrophages, upregulated MMP-9 and stimulated MMP-9-dependent transmigration across endothelial cell monolayers by 2.6-fold. There was a reduction in F4/80+ macrophages in spinal cord-injured MMP-9 knock-out mice (by 36%) or wild-type mice, treated with the broad-spectrum MMP inhibitor GM6001 (by 30%). Mice were adoptively transferred with myeloid cells and treated with the MMP-9/-2 inhibitor SB-3CT, the CXCR4 antagonist AMD3100, or a combination of both drugs. While either drug resulted in a 28-30% reduction of infiltrated myeloid cells, the combined treatment resulted in a 45% reduction, suggesting that SDF-1 and MMP-9 function independently to promote the trafficking of myeloid cells into the injured cord. Collectively, these observations suggest a synergistic partnership between MMP-9 and SDF-1 in facilitating transmigration of monocytes into the injured spinal cord.

  11. Immobilized Artificial Membrane HPLC Derived Parameters vs PAMPA-BBB Data in Estimating in Situ Measured Blood-Brain Barrier Permeation of Drugs.

    Science.gov (United States)

    Grumetto, Lucia; Russo, Giacomo; Barbato, Francesco

    2016-08-01

    The affinity indexes for phospholipids (log kW(IAM)) for 42 compounds were measured by high performance liquid chromatography (HPLC) on two different phospholipid-based stationary phases (immobilized artificial membrane, IAM), i.e., IAM.PC.MG and IAM.PC.DD2. The polar/electrostatic interaction forces between analytes and membrane phospholipids (Δlog kW(IAM)) were calculated as the differences between the experimental values of log kW(IAM) and those expected for isolipophilic neutral compounds having polar surface area (PSA) = 0. The values of passage through a porcine brain lipid extract (PBLE) artificial membrane for 36 out of the 42 compounds considered, measured by the so-called PAMPA-BBB technique, were taken from the literature (P0(PAMPA-BBB)). The values of blood-brain barrier (BBB) passage measured in situ, P0(in situ), for 38 out of the 42 compounds considered, taken from the literature, represented the permeability of the neutral forms on "efflux minimized" rodent models. The present work was aimed at verifying the soundness of Δlog kW(IAM) at describing the potential of passage through the BBB as compared to data achieved by the PAMPA-BBB technique. In a first instance, the values of log P0(PAMPA-BBB) (32 data points) were found significantly related to the n-octanol lipophilicity values of the neutral forms (log P(N)) (r(2) = 0.782) whereas no significant relationship (r(2) = 0.246) was found with lipophilicity values of the mixtures of ionized and neutral forms existing at the experimental pH 7.4 (log D(7.4)) as well as with either log kW(IAM) or Δlog kW(IAM) values. log P0(PAMPA-BBB) related moderately to log P0(in situ) values (r(2) = 0.604). The latter did not relate with either n-octanol lipophilicity indexes (log P(N) and log D(7.4)) or phospholipid affinity indexes (log kW(IAM)). In contrast, significant inverse linear relationships were observed between log P0(in situ) (38 data points) and Δlog kW(IAM) values for all the compounds but

  12. CD34 expression modulates tube-forming capacity and barrier properties of peripheral blood-derived endothelial colony-forming cells (ECFCs).

    Science.gov (United States)

    Tasev, Dimitar; Konijnenberg, Lara S F; Amado-Azevedo, Joana; van Wijhe, Michiel H; Koolwijk, Pieter; van Hinsbergh, Victor W M

    2016-07-01

    Endothelial colony-forming cells (ECFC) are grown from circulating CD34(+) progenitors present in adult peripheral blood, but during in vitro expansion part of the cells lose CD34. To evaluate whether the regulation of CD34 characterizes the angiogenic phenotypical features of PB-ECFCs, we investigated the properties of CD34(+) and CD34(-) ECFCs with respect to their ability to form capillary-like tubes in 3D fibrin matrices, tip-cell gene expression, and barrier integrity. Selection of CD34(+) and CD34(-) ECFCs from subcultured ECFCs was accomplished by magnetic sorting (FACS: CD34(+): 95 % pos; CD34(-): 99 % neg). Both fractions proliferated at same rate, while CD34(+) ECFCs exhibited higher tube-forming capacity and tip-cell gene expression than CD3(4-) cells. However, during cell culture CD34(-) cells re-expressed CD34. Cell-seeding density, cell-cell contact formation, and serum supplements modulated CD34 expression. CD34 expression in ECFCs was strongly suppressed by newborn calf serum. Stimulation with FGF-2, VEGF, or HGF prepared in medium supplemented with 3 % albumin did not change CD34 mRNA or surface expression. Silencing of CD34 with siRNA resulted in strengthening of cell-cell contacts and increased barrier function of ECFC monolayers as measured by ECIS. Furthermore, CD34 siRNA reduced tube formation by ECFC, but did not affect tip-cell gene expression. These findings demonstrate that CD34(+) and CD34(-) cells are different phenotypes of similar cells and that CD34 (1) can be regulated in ECFC; (2) is positively involved in capillary-like sprout formation; (3) is associated but not causally related to tip-cell gene expression; and (4) can affect endothelial barrier function.

  13. Mesenchymal stem cells promote a primitive phenotype CD34+c-kit+ in human cord blood-derived hematopoietic stem cells during ex vivo expansion.

    Science.gov (United States)

    Rodríguez-Pardo, Viviana M; Vernot, Jean Paul

    2013-03-01

    The purpose of this study was to evaluate the influence of bone marrow-mesenchymal stem cells (BM-MSC) and exogenously added cytokines on the proliferation, primitive cell subpopulation maintenance (including the c-kit+ marker) and clonogenic capacity of hematopoietic stem cells (HSC). BM-MSC were collected from volunteer donors, isolated and characterized. Umbilical cord blood (UCB) samples were collected from healthy full-term deliveries. UCB-CD34+ cells were cultured in the presence or absence of BM-MSC and/or cytokines for 3 and 7 days. CD34+ cell proliferation was evaluated using the CSFE method and cell phenotype was determined by CD34, c-kit, CD33, CD38, HLA-DR, cyCD22 and cyCD3 detection. Cell clonogenic ability was also assessed. Exogenously added SCF, TPO and FLT3L increased CD34+ cell proliferation in the presence or absence of BM-MSC, but with concomitant cell differentiation. Without any added cytokines, BM-MSC are able to increase the percentage of primitive progenitors as evaluated by c-kit expression and CFU-GEMM increase. Interestingly, this latter effect was dependent on both cell-cell interactions and secreted factors. A 7-day co-culture period will be optimal for obtaining an increased primitive HSC level. Including c-kit as a marker for primitive phenotype evaluation has shown the relevance of BM-MSC and their secreted factors on UCB-HSC stemness function. This effect could be dissociated from that of the addition of exogenous cytokines, which induced cellular differentiation instead.

  14. Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells

    Institute of Scientific and Technical Information of China (English)

    YiZhanga; ChangdongLi; XiaoxiaJiang; ShuangxiZhang; YingWu; BingLiu; PeihsienTang; NingMao

    2005-01-01

    Objective. Allogeneic transplantation with umbilical cord blood (UCB) in adult recipients is limited mainly by a low CD34+ cell dose. To overcome this shortcoming, human placenta as a novel source of human mesenchymal progenitor cell (MPC) was incorporated in an attempt to expand CD34+ ceils from UCB in vitro.Materials and Methods. Human placenta MPC was isolated and characterized by morphologic,immunophenotypical, and functional analysis. UCB CD34+ cells were expanded by coculturewith placeutal MPC. Suitable aliquots of cells were used to monitor cell production, elonogenie activity, and tong-term culture-initiating culture (LTC-IC) output. Finally, the immunoregulatory effect of placental MPC was evaluated by T-cell proliferation assay.Results. In its undifferentiated state, placental MPC displayed fibroblastoid morphology; was CD73, CD105, CD29, CD44, HLA-ABC, and CD166 positive; produced fibronectin, laminin,and vimentin; but was negative for CD14, CD31, CD34, CD45, HLA-DR, and α-smooth muscle actin. Functionally, it could be induced into adipocytes, osteocytes, and chondrocytes.In vitro expansion of UCB hematopoietic cells, when cocultured with placental MPC in the presence of eytokines, was significantly enhanced: CD34+ cells by 14.89±2.32 fold; colonyforming cell (CFC) by 36.73±5.79 told; and LTC-IC by 7.43±2.66 fold. Moreover, placental MPC could suppress T-cell proliferation induced by cellular stimuli.Conclusion. These results strongly suggest that human placental MPC may be a suitable feeder layer for expansion of hematopoietic progenitors from UCB in vitro.

  15. Effect of Single and Double Administration of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Following Focal Cerebral Ischemia in Rats

    Science.gov (United States)

    Park, Hyung Woo; Kim, Yona; Chang, Jong Wook; Yang, Yoon Sun; Oh, Wonil; Lee, Jae Min; Park, Hye Ran; Kim, Dong Gyu

    2017-01-01

    Stem cell therapies are administered during the acute phase of stroke to preserve the penumbral tissues from ischemic injury. However, the effect of repeated cell therapy during the acute phase remains unclear. In this study, we investigated and compared the functional outcome of single (two days post-injury) and repeated (two and nine days post-injury) treatment with human umbilical cord derived mesenchymal stem cells (hUCB-MSCs) after middle cerebral artery occlusion (MCAO). The rotarod and limb placement tests were utilized to investigate functional outcomes, while infarct volume and tissue damage were measured by immunofluorescent staining for neovascularization, neurogenesis, apoptosis, and inflammation in the penumbral zones. We observed notable motor dysfunction and a significant decrease in infarcted brain volume, as well as increases in neurons and vessels in both single and repeated hUCB-MSC treatments compared to the control group. Interestingly, repeated administration of hUCB-MSCs was not found to elicit additional or synergistic improvements over monotherapy. This study suggests that a clearer understanding of the therapeutic window after stroke will facilitate the development of more efficient treatment protocols in the clinical application of stem cell therapy. PMID:28243167

  16. Therapeutic isolation and expansion of human skeletal muscle-derived stem cells for the use of muscle-nerve-blood vessel reconstitution

    Directory of Open Access Journals (Sweden)

    Tetsuro eTamaki

    2015-06-01

    Full Text Available Skeletal muscle makes up 40-50% of body mass, and is thus considered to be a good adult stem cell source for autologous therapy. Although, several stem/progenitor cells have been fractionated from mouse skeletal muscle showing a high potential for therapeutic use, it is unclear whether this is the case in human. Differentiation and therapeutic potential of human skeletal muscle-derived cells (Sk-Cs was examined. Samples (5-10 g were obtained from the abdominal and leg muscles of 36 patients (age, 17-79 years undergoing prostate cancer treatment or leg amputation surgery. All patients gave informed consent. Sk-Cs were isolated using conditioned collagenase solution, and were then sorted as CD34-/CD45-/CD29+ (Sk-DN/29+ and CD34+/CD45- (Sk-34 cells, in a similar manner as for the previous mouse Sk-Cs. Both cell fractions were appropriately expanded using conditioned culture medium for about 2 weeks. Differentiation potentials were then examined during cell culture and in vivo transplantation into the severely damaged muscles of athymic nude mice and rats. Interestingly, these two cell fractions could be divided into highly myogenic (Sk-DN/29+ and multipotent stem cell (Sk-34 fractions, in contrast to mouse Sk-Cs, which showed comparable capacities in both cells. At 6 weeks after the separate transplantation of both cell fractions, the former showed an active contribution to muscle fiber regeneration, but the latter showed vigorous engraftment to the interstitium associated with differentiation into Schwann cells, perineurial/endoneurial cells, and vascular endothelial cells and pericytes, which corresponded to previous observations with mouse SK-Cs. Importantly, mixed cultures of both cells resulted the reduction of tissue reconstitution capacities in vivo, whereas co-transplantation after separate expansion showed favorable results. Therefore, human Sk-Cs are potentially applicable to therapeutic autografts and show multiple differentiation

  17. Blood-type distribution

    Science.gov (United States)

    Kim, Beom Jun; Myeong Lee, Dong; Hun Lee, Sung; Gim, Wan-Suk

    2007-01-01

    We statistically verify the Hardy-Weinberg principle in genetics by investigating the independence of ABO-blood types of married couples. The allelic frequencies derived from the phenotypic frequencies in ethnic groups via the Hardy-Weinberg principle are used to define a genetic distance (called the blood distance in this work) between two groups. The blood distances are compared with the geographic distances, and then used to construct a network of ethnic groups. We also investigate the relationship between the ABO blood types and the human personalities, gauged by the Myers-Briggs-type indicator (MBTI) psychological test. The statistical χ2-test reveals the independence between the blood types and MBTI results with an exception of type B males. A psychological implication is discussed.

  18. Compliance of Ischemic State Tissue on Stem Cells Derived Angiology for Secondary Blood Flow Remodeling%干细胞源性血管重建缺血态组织血供的临床研究

    Institute of Scientific and Technical Information of China (English)

    高雪; 曾希云; 杨镛

    2012-01-01

    Objective To investigate the biological mechanism about autologous peripheral blood stem cell transplantation (ABSCT) derived neovascularization to lead and perfect the effect of ischemic state tissue of secondary blood flow remodeling. Methods Forty-two patients with critical limbs ischemia and 42 limbs in all from Mar. 2005 to Dec. 2005 in Yunnan Provincial Center of Vascular Surgery were selected, who treated by endovascular repair and ABSCT at the first flow reconstruction and the secondary flow reconstruction, respectively. The preoperative and postoperative effect degrees of limbs regional blood flow from cutaneous covering, blood vessel, and blood were measured by multifunction monitoring device, dopplor ultrasound monitoring device, percutem oxygen partial pressure (TcPO2) monitoring device and digital subtraction angiography (DSA). The follow-up time was in four year after ABSCT. Results After ABSCT, the pain, cold or cool, and rest pain of leg were relieved The distance of intermittent claudica-tion after ABSCT was longer than that before ABSCT [ (1 600. 3 ± 310. 1) m versus (520. 3 ± 160. 6) m, F=5. 84, P< 0. 05]. The foot pain and limbs insensible feeling easement rates were 100% after ABSCT. Compared with before ABSCT,the objective effect indexes of limbs regional blood flow after ABSCT were significantly improved [skin temperature index: 1.63 + 0.31 versus \\.22±0. 23,F=4. 69,P<0. 05; TcPO2: (37. 61+9. 52) mmHg versus (30. 63+4. 54) mmHg, F=5.72,P<0. 05; ankle-brachium index: 0. 93 + 0. 23 versus 0. 33 + 0. 24, F=6. 72, P<0. 05; photoplethys-mography index: 0. 81+0. 12 versus 0. 23±0. 05, F=5. 68, P<0. 05; saturation of blood oxygen: (79.44±20.42) % versus(42.43+10.41) %,F=5.68,P<0.05; DSAscore: 1.34±0.23 versus0.21±0.03,F=4. 89,.P<0.05]. Conclusions The results strongly suggest that the ABSCT can promote blood flow remodeling in limbs ischemia, and stem cells derived neovascularization can significantly offer effective and permanent blood flow

  19. Artificial blood

    Directory of Open Access Journals (Sweden)

    Sarkar Suman

    2008-01-01

    Full Text Available Artificial blood is a product made to act as a substitute for red blood cells. While true blood serves many different functions, artificial blood is designed for the sole purpose of transporting oxygen and carbon dioxide throughout the body. Depending on the type of artificial blood, it can be produced in different ways using synthetic production, chemical isolation, or recombinant biochemical technology. Development of the first blood substitutes dates back to the early 1600s, and the search for the ideal blood substitute continues. Various manufacturers have products in clinical trials; however, no truly safe and effective artificial blood product is currently marketed. It is anticipated that when an artificial blood product is available, it will have annual sales of over $7.6 billion in the United States alone.

  20. Artificial blood.

    Science.gov (United States)

    Sarkar, Suman

    2008-07-01

    Artificial blood is a product made to act as a substitute for red blood cells. While true blood serves many different functions, artificial blood is designed for the sole purpose of transporting oxygen and carbon dioxide throughout the body. Depending on the type of artificial blood, it can be produced in different ways using synthetic production, chemical isolation, or recombinant biochemical technology. Development of the first blood substitutes dates back to the early 1600s, and the search for the ideal blood substitute continues. Various manufacturers have products in clinical trials; however, no truly safe and effective artificial blood product is currently marketed. It is anticipated that when an artificial blood product is available, it will have annual sales of over $7.6 billion in the United States alone.

  1. 全血硫胺素及其衍生物的高效液相色谱检测方法的建立%HPLC determination of thiamine and its derivatives in human whole blood

    Institute of Scientific and Technical Information of China (English)

    费国强; 李晓鸽; 钟春玖

    2012-01-01

    目的 建立一种稳定、快捷的全血硫胺素及其磷酸酯衍生物高效液相色谱( HPLC)荧光检测方法.方法 全血样本经三氯乙酸(TCA)去蛋白处理、铁氰化钾衍生,产生能被HPLC反向柱子经梯度洗脱分离的稳定荧光产物,通过荧光检测并与硫胺素及其磷酸酯衍生物标准样本比对,来确定人体全血硫胺素含量.方法通过线性方程、提取率、重复性等指标验证.结果 经过检测,焦磷酸硫胺素(TDP)、单磷酸硫胺素(TMP)和硫胺素的检测限分别为8.0、1.5和2.5 nmol/L,信噪比(S/N) >10,能够满足临床需要.线性趋势良好,r>0.99.硫胺素、TMP及TDP的回收率分别为103.7%、96.8%、101.7%,重复性好,变异系数(CV)<10%.结论 经TCA去蛋白、铁氰化钾衍生、梯度洗脱建立的荧光HPLC检测硫胺素及其磷酸酯衍生物衍生物的方法可靠,可用于临床检测.%Objective To establish a stable and rapid method for determining the levels of human whole blood thiamine and its phosphate ester derivatives by high performance liquid chromatography (HPLC). Methods After blood proteins were precipitated by trichloroacetic acid (TCA), thiamine and its phosphate esters were derivatized using potassium ferricyanide into thioehromes. The derivatives of thiamine and it phosphate esters were separated by a reversed-phase HPLC column and measured by fluoroscope. The method was validated by the analysis of linearity, extraction ratio and repeatability. Results The lower limits of quantification of blood thiamine diphosphate (TDP), thiamin monophosphate (TMP) and thiamine determinations were 8.0, 1.5 and 2.5nmol/L respectively. The signal to noise ratio (S/N) for determining thiamine and its derivatives was > 10. The linear relationship was stable (r >0.99). The recovery rates of TDP. TMP and thiamine were 103.1% , 96. 8% and 101. 7% respectively. The repeatabilities were good. All the coefficients of variation (CV) were < 10%. Conclusions

  2. Blood Clots

    Science.gov (United States)

    ... or prevent blood clots from dissolving properly. Risk factors for excessive blood clotting include Certain genetic disorders Atherosclerosis Diabetes Atrial fibrillation Overweight, obesity, and metabolic syndrome Some medicines Smoking deep vein ...

  3. Blood Transfusion

    Science.gov (United States)

    ... to their work or home. The availability of plastic bags that can have one or more satellite bags ... in preparing the donated blood. The use of plastic bags allows the blood center to make a variety ...

  4. Graft monocytic myeloid-derived suppressor cell content predicts the risk of acute graft-versus-host disease after allogeneic transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells.

    Science.gov (United States)

    Vendramin, Antonio; Gimondi, Silvia; Bermema, Anisa; Longoni, Paolo; Rizzitano, Sara; Corradini, Paolo; Carniti, Cristiana

    2014-12-01

    Myeloid-derived suppressor cells (MDSCs) are powerful immunomodulatory cells that in mice play a role in infectious and inflammatory disorders, including acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Their relevance in clinical acute GVHD is poorly known. We analyzed whether granulocyte colony-stimulating factor (G-CSF) administration, used to mobilize hematopoietic stem cells, affected the frequency of MDSCs in the peripheral blood stem cell grafts of 60 unrelated donors. In addition, we evaluated whether the MDSC content in the peripheral blood stem cell grafts affected the occurrence of acute GVHD in patients undergoing unrelated donor allogeneic stem cell transplantation. Systemic treatment with G-CSF induces an expansion of myeloid cells displaying the phenotype of monocytic MDSCs (Lin(low/neg)HLA-DR(-)CD11b(+)CD33(+)CD14(+)) with the ability to suppress alloreactive T cells in vitro, therefore meeting the definition of MDSCs. Monocytic MDSC dose was the only graft parameter to predict acute GVHD. The cumulative incidence of acute GVHD at 180 days after transplantation for recipients receiving monocytic MDSC doses below and above the median was 63% and 22%, respectively (P = .02). The number of monocytic MDSCs infused did not impact the relapse rate or the transplant-related mortality rate (P > .05). Although further prospective studies involving larger sample size are needed to validate the exact monocytic MDSC graft dose that protects from acute GVHD, our results strongly suggest the modulation of G-CSF might be used to affect monocytic MDSCs graft cell doses for prevention of acute GVHD.

  5. Blood Facts and Statistics

    Science.gov (United States)

    ... Facts and Statistics Printable Version Blood Facts and Statistics Facts about blood needs Facts about the blood ... to Top Learn About Blood Blood Facts and Statistics Blood Components Whole Blood and Red Blood Cells ...

  6. Cord Blood

    Directory of Open Access Journals (Sweden)

    Saeed Abroun

    2014-05-01

    Full Text Available   Stem cells are naïve or master cells. This means they can transform into special 200 cell types as needed by body, and each of these cells has just one function. Stem cells are found in many parts of the human body, although some sources have richer concentrations than others. Some excellent sources of stem cells, such as bone marrow, peripheral blood, cord blood, other tissue stem cells and human embryos, which last one are controversial and their use can be illegal in some countries. Cord blood is a sample of blood taken from a newborn baby's umbilical cord. It is a rich source of stem cells, umbilical cord blood and tissue are collected from material that normally has no use following a child’s birth. Umbilical cord blood and tissue cells are rich sources of stem cells, which have been used in the treatment of over 80 diseases including leukemia, lymphoma and anemia as bone marrow stem cell potency.  The most common disease category has been leukemia. The next largest group is inherited diseases. Patients with lymphoma, myelodysplasia and severe aplastic anemia have also been successfully transplanted with cord blood. Cord blood is obtained by syringing out the placenta through the umbilical cord at the time of childbirth, after the cord has been detached from the newborn. Collecting stem cells from umbilical blood and tissue is ethical, pain-free, safe and simple. When they are needed to treat your child later in life, there will be no rejection or incompatibility issues, as the procedure will be using their own cells. In contrast, stem cells from donors do have these potential problems. By consider about cord blood potency, cord blood banks (familial or public were established. In IRAN, four cord blood banks has activity, Shariati BMT center cord blood bank, Royan familial cord blood banks, Royan public cord blood banks and Iranian Blood Transfusion Organ cord blood banks. Despite 50,000 sample which storage in these banks, but the

  7. Acanthamoeba castellanii Genotype T4 Stimulates the Production of Interleukin-10 as Well as Proinflammatory Cytokines in THP-1 Cells, Human Peripheral Blood Mononuclear Cells, and Human Monocyte-Derived Macrophages.

    Science.gov (United States)

    Mattana, Antonella; Sanna, Manuela; Cano, Antonella; Delogu, Giuseppe; Erre, Giuseppe; Roberts, Craig W; Henriquez, Fiona L; Fiori, Pier Luigi; Cappuccinelli, Piero

    2016-10-01

    Free-living amoebae of the genus Acanthamoeba can cause severe and chronic infections in humans, mainly localized in immune privileged sites, such as the brain and the eye. Monocytes/macrophages are thought to be involved in Acanthamoeba infections, but little is known about how these facultative parasites influence their functions. The aim of this work was to investigate the effects of Acanthamoeba on human monocytes/macrophages during the early phase of infection. Here, THP-1 cells, primary human monocytes isolated from peripheral blood, and human monocyte-derived macrophages were either coincubated with trophozoites of a clinical isolate of Acanthamoeba (genotype T4) or stimulated with amoeba-derived cell-free conditioned medium. Production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and IL-12), anti-inflammatory cytokine (IL-10), and chemokine (IL-8) was evaluated at specific hours poststimulation (ranging from 1.5 h to 23 h). We showed that both Acanthamoeba trophozoites and soluble amoebic products induce an early anti-inflammatory monocyte-macrophage phenotype, characterized by significant production of IL-10; furthermore, challenge with either trophozoites or their soluble metabolites stimulate both proinflammatory cytokines and chemokine production, suggesting that this protozoan infection results from the early induction of coexisting, opposed immune responses. Results reported in this paper confirm that the production of proinflammatory cytokines and chemokines by monocytes and macrophages can play a role in the development of the inflammatory response during Acanthamoeba infections. Furthermore, we demonstrate for the first time that Acanthamoeba stimulates IL-10 production in human innate immune cells, which might both promote the immune evasion of Acanthamoeba and limit the induced inflammatory response.

  8. Acanthamoeba castellanii Genotype T4 Stimulates the Production of Interleukin-10 as Well as Proinflammatory Cytokines in THP-1 Cells, Human Peripheral Blood Mononuclear Cells, and Human Monocyte-Derived Macrophages

    Science.gov (United States)

    Sanna, Manuela; Cano, Antonella; Delogu, Giuseppe; Erre, Giuseppe; Roberts, Craig W.; Henriquez, Fiona L.; Fiori, Pier Luigi; Cappuccinelli, Piero

    2016-01-01

    Free-living amoebae of the genus Acanthamoeba can cause severe and chronic infections in humans, mainly localized in immune privileged sites, such as the brain and the eye. Monocytes/macrophages are thought to be involved in Acanthamoeba infections, but little is known about how these facultative parasites influence their functions. The aim of this work was to investigate the effects of Acanthamoeba on human monocytes/macrophages during the early phase of infection. Here, THP-1 cells, primary human monocytes isolated from peripheral blood, and human monocyte-derived macrophages were either coincubated with trophozoites of a clinical isolate of Acanthamoeba (genotype T4) or stimulated with amoeba-derived cell-free conditioned medium. Production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and IL-12), anti-inflammatory cytokine (IL-10), and chemokine (IL-8) was evaluated at specific hours poststimulation (ranging from 1.5 h to 23 h). We showed that both Acanthamoeba trophozoites and soluble amoebic products induce an early anti-inflammatory monocyte-macrophage phenotype, characterized by significant production of IL-10; furthermore, challenge with either trophozoites or their soluble metabolites stimulate both proinflammatory cytokines and chemokine production, suggesting that this protozoan infection results from the early induction of coexisting, opposed immune responses. Results reported in this paper confirm that the production of proinflammatory cytokines and chemokines by monocytes and macrophages can play a role in the development of the inflammatory response during Acanthamoeba infections. Furthermore, we demonstrate for the first time that Acanthamoeba stimulates IL-10 production in human innate immune cells, which might both promote the immune evasion of Acanthamoeba and limit the induced inflammatory response. PMID:27481240

  9. Patient Blood Management in Europe

    DEFF Research Database (Denmark)

    Bruun, M T; Pendry, K; Georgsen, J

    2016-01-01

    BACKGROUND AND OBJECTIVES: Patient Blood Management (PBM) in Europe is a working group of the European Blood Alliance with the initial objective to identify the starting position of the participating hospitals regarding PBM for benchmarking purposes, and to derive good practices in PBM from...

  10. Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Christophe M Raynaud

    Full Text Available Mesenchymal progenitors or stromal cells have shown promise as a therapeutic strategy for a range of diseases including heart failure. In this context, we explored the growth and differentiation potential of mesenchymal progenitors (MPs derived in vitro from human embryonic stem cells (hESCs. Similar to MPs isolated from bone marrow, hESC derived MPs (hESC-MPs efficiently differentiated into archetypical mesenchymal derivatives such as chondrocytes and adipocytes. Upon treatment with 5-Azacytidine or TGF-β1, hESC-MPs modified their morphology and up-regulated expression of key cardiac transcription factors such as NKX2-5, MEF2C, HAND2 and MYOCD. Nevertheless, NKX2-5+ hESC-MP derivatives did not form contractile cardiomyocytes, raising questions concerning the suitability of these cells as a platform for cardiomyocyte replacement therapy. Gene profiling experiments revealed that, although hESC-MP derived cells expressed a suite of cardiac related genes, they lacked the complete repertoire of genes associated with bona fide cardiomyocytes. Our results suggest that whilst agents such as TGF-β1 and 5-Azacytidine can induce expression of cardiac related genes, but treated cells retain a mesenchymal like phenotype.

  11. The effects of concentrate added to pineapple (Ananas comosus Linn. Mer.) waste silage in differing ratios to form complete diets, on digestion, excretion of urinary purine derivatives and blood metabolites in growing, male, Thai swamp buffaloes.

    Science.gov (United States)

    Jetana, T; Suthikrai, W; Usawang, S; Vongpipatana, C; Sophon, S; Liang, J B

    2009-04-01

    Four, male, growing Thai swamp buffaloes (197 +/- 5.3 kg and all 1 year old) were used to evaluate the effects of concentrate added to pineapple waste silage in differing ratios, to form a complete diet, studying in vivo digestion, the rate of passage, microbial protein synthesis and blood metabolites. Animals were fed ad libitum with 4 diets, using four combinations of pineapple waste silage (P) and concentrate (C), in the proportions (on a dry matter basis) of 0.8:0.2 (P80:C20), 0.6:0.4 (P60:C40), 0.4:0.6 (P40:C60) and 0.2:0.8 (P20:C80). The results showed that the intakes of dry matter (DM), organic matter (OM), nitrogen (N), the N-balance, urinary purine derivatives (PD) excretion, the ratios of allantoin to creatinine (CR), PD to CR, the plasma urea-N (PUN) and insulin increased in the animals, but the intake of neutral detergent fiber (NDF), the coefficient of whole tract, apparent digestibility of NDF, the transit time (TT) and the mean retention time (TMRT) decreased, when the proportion of concentrate in the diet increased. This study indicated that the proportion of P40:C60 in the diet produced the best efficiency of urinary PD excretion (mmol) per digestible OM intake (kg DOMI).

  12. Immunoelectrophoresis - blood

    Science.gov (United States)

    IEP - serum; Immunoglobulin electrophoresis - blood; Gamma globulin electrophoresis; Serum immunoglobulin electrophoresis; Amyloidosis - electrophoresis serum; Multiple myeloma - serum electrophoresis; Waldenström - serum electrophoresis

  13. Amphetamine derivative related deaths.

    Science.gov (United States)

    Lora-Tamayo, C; Tena, T; Rodríguez, A

    1997-02-28

    Amphetamine its methylendioxy (methylendioxyamphetamine methylenedioxymethylamphetamine, methylenedioxyethylamphetamine) and methoxy derivatives (p-methoxyamphetamine and p-methoxymethylamphetamine) are widely abused in Spanish society. We present here the results of a systematic study of all cases of deaths brought to the attention of the Madrid department of the Instituto Nacional de Toxicologia from 1993 to 1995 in which some of these drugs have been found in the cadaveric blood. The cases were divided into three categories: amphetamine and derivatives, amphetamines and alcohol, amphetamines and other drugs. Data on age, sex, clinical symptoms, morphological findings, circumstances of death, when known, and concentration of amphetamine derivatives, alcohol and other drugs in blood are given for each group. The information provided here may prove to be useful for the forensic interpretation of deaths which are directly or indirectly related to abuse of amphetamine derivatives.

  14. Understanding Blood Counts

    Science.gov (United States)

    ... Lab and Imaging Tests Understanding Blood Counts Understanding Blood Counts Understanding Blood Counts SHARE: Print Glossary Blood cell counts give ... your blood that's occupied by red cells. Normal Blood Counts Normal blood counts fall within a range ...

  15. BLOOD DONATION

    CERN Multimedia

    SC Unit

    2008-01-01

    A blood donation, organized by EFS (Etablissement Français du Sang) of Annemasse will take place On Wednesday 12 November 2008, from 8:30 to 16:00, at CERN Restaurant 2 If possible, please, bring your blood group Card.

  16. Blood donation

    CERN Multimedia

    GS Department

    2009-01-01

    A blood donation is organised by the Cantonal Hospital of Geneva On Thursday 19 March 2009 from 9 a.m. to 5 p.m. CERN RESTAURANT 2 Number of donations during the last blood donations :135 donors in July 2008 122 donors in November 2008 Let’s do better in 2009 !!! Give 30 minutes of your time to save lives...

  17. Efficacy and safety of cord blood-derived dendritic cells plus cytokine-induced killer cells combined with chemotherapy in the treatment of patients with advanced gastric cancer: a randomized Phase II study

    Directory of Open Access Journals (Sweden)

    Mu Y

    2016-07-01

    Full Text Available Ying Mu,1,* Wei-hua Wang,2,* Jia-ping Xie,1 Ying-xin Zhang,2 Ya-pei Yang,2 Chang-hui Zhou2 1Department of Gastroenterology, 2Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong Province, People’s Republic of China *These authors contributed equally to this work Background: Cellular immunotherapy has been widely used in the treatment of solid tumors. However, the clinical application of cord blood-derived dendritic cells and cytokine-induced killer cells (CB-DC-CIK for the treatment of gastric cancer has not been frequently reported. In this study, the efficacy and safety of CB-DC-CIK for the treatment of gastric cancer were evaluated both in vitro and in vivo. Methods: The phenotypes, cytokines, and cytotoxicity of CB-DC-CIK were detected in vitro. Patients with advanced gastric cancer were divided into the following two groups: the experimental group (CB-DC-CIK combined with chemotherapy and the control group (chemotherapy alone. The curative effects and immune function were compared between the two groups. Results: First, the results showed that combination therapy significantly increased the overall disease-free survival rate (P=0.0448 compared with chemotherapy alone. The overall survival rate (P=0.0646, overall response rate (P=0.410, and disease control rate (P=0.396 were improved in the experimental group, but these changes did not reach statistical significance. Second, the percentage of T-cell subsets (CD4+, CD3-CD56+, and CD3+CD56+ and the levels of IFN-γ, TNF-α, and IL-2, which reflect immune function, were significantly increased (P<0.05 after immunotherapy. Finally, no serious side effects appeared in patients with gastric cancer after the application of cellular immunotherapy based on CB-DC-CIK. Conclusion: CB-DC-CIK combined with chemotherapy is effective and safe for the treatment of patients with advanced gastric cancer. Keywords: cord

  18. Tainted blood

    DEFF Research Database (Denmark)

    Deleuran, Ida; Sheikh, Zainab Afshan; Hoeyer, Klaus

    2015-01-01

    study of the historical rise and current workings of safety practices in the Danish blood system. Here, we identify a strong focus on contamination in order to avoid 'tainted blood', at the expense of working with risks that could be avoided through enhanced blood monitoring practices. Of further...... significance to this focus are the social dynamics found at the heart of safety practices aimed at avoiding contamination. We argue that such dynamics need more attention, in order to achieve good health outcomes in transfusion medicine. Thus, we conclude that, to ensure continuously safe blood systems, we...... need to move beyond the bifurcation of the social and medical aspects of blood supply as two separate issues and approach social dynamics as key medical safety questions....

  19. What Happens to Donated Blood?

    Science.gov (United States)

    ... week. Learn About Blood Blood Facts and Statistics Blood Components Whole Blood and Red Blood Cells Platelets Plasma ... About Blood Blood Facts and Statistics Blood Types Blood Components What Happens to Donated Blood Blood and Diversity ...

  20. Diagnostic value of platelet derived growth factor-BB, transforming growth factor-β1,matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinase-1 in serum and peripheral blood mononuclear cells for hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Bin-Bin Zhang; Wei-Min Cai; Hong-Lei Weng; Zhong-Rong Hu; Jun Lu; Min Zheng; Rong-Hua Liu

    2003-01-01

    AIM: Noninvasive diagnosis of hepatic fibrosis has become the focus because of the limited biopsy, especially in the surveillance of treatment and in screening hepatic fibrosis.Recently, regulatory elements involved in liver fibrosis, such as platelet derived growth factor-BB (PDGF-BB), transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), have been studied extensively. To determine whether these factors or enzymes could be used as the indices for the diagnosis of hepatic fibrosis, we investigated them by means of receiver operating characteristic (ROC) curve.METHODS: Serum samples from sixty patients with chronic viral hepatitis B and twenty healthy blood donors were assayed to determine the level of PDGF-BB, TGF-β1, MMP-1, and TIMP-1 with ELISA, and HA, PCIII, C-IV, and LN level with RIA. The message RNA (mRNA) expression of TIMP-1 and MMP-1 in peripheral blood mononuclear cells (PBMCs) was detected by RT-PCR and Northern blot hybridization. Liver biopsy was performed in all patients.The biopsy samples were histopathologically examined. The trial was double-blind controlled.RESULTS: The serum level of PDGF-BB, TIMP-1, the ratio of TIMP-1 and MMP-1 (TIMP-1/MMP-1), mRNA expression of TIMP-1 (TIMP-1mRNA), and the ratio of TIMP-1mRNA and MMP-1mRNA (TIMP-1mRNA/MMP-1mRNA) in patients was significantly higher than those in the healthy blood donors (t=2.514-11.435, P=0.000-0.016). The serum level of PDGF-BB, TIMP-1, TIMP-1/MMP-1, and TIMP-1mRNA was positively correlated with fibrosis stage and inflammation grade (r=0.239-0.565, P=0.000-0.033), while the serum level of MMP-1 was negatively correlated with fibrosis stage and inflammation grade, and TIMP-1mRNA/MMP-1mRNA was positively correlated with inflammation grade. Through the analysis by ROC curve, serum PDGF-BB was the most valuable marker, and its sensitivity was the highest among the nine indices. The markers with the highest

  1. A novel,rapid strategy to form dendritomas from human dendritic cells and hepatocellular carcinoma cell line HCCLM3 cells using mature dendritic cells derived from human peripheral blood CD14+monocytes within 48 hours of in vitro culture

    Institute of Scientific and Technical Information of China (English)

    Xin Guan; Ji-Run Peng; Lan Yuan; Hui Wang; Yu-Hua Wei; Xi-Sheng Leng

    2004-01-01

    AIM: Dendritomas formed by fusing cancer cells to dendritic cells have already been applied to clinical treatment trial of several types of cancers. Dendritic cells for the fusion in most trials and experiments were from blood monocytes in standard 7-d protocol culture, which requires 5-7 d of culture with granulocyte-macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), followed by 2-3 d of activation with a combination of proinflammatory mediators such as tumor necrosis factorα (TNFα), interleukin1β (IL-1β), interleukin-6 (IL-6)and prostaglandin E2 (PGE2).One study showed that mature monocyte-derived dendritic cells could be obtained within 48 h ofin vitro culture with the same protocol as standard 7-d culture and referred to as FastDCs. Here we aimed to fuse human hepatocellular carcinoma cell line HCCLM3 cells with mature monocytederived dendritic cells within 48 h ofin vitro culture (FastDC).METHODS: HCCLMl3 cells were cultured in RPMI 1640 with 150 mL/L fetal calf serum (FCS). CD14+monocytes from healthy human peripheral blood were purified with MACS CD14 isolation kit and cultured in six-well plates in fresh complete DC medium containing RPMI-1640, 20 mL/Lheat inactivated human AB serum, 2 mmol/L L-glutamine,100 μg/mL gentamicin, 1000 U/mL GM-CSF and 500 U/mL IL-4 for 24 h, then proinflammatory mediators such as TNFα(1000 U/mL), IL-1β (10 ng/mL), IL-6 (10 ng/mL) and PGE2(1μg/mL) were supplemented for another 24 h, and thus mature FastDCs were generated. HCCLM3 cells and FastDCs were labeled with red fluorescent dye PKH26-GL and green fluorescent dye PKH67-GL respectively. After the red fluorescent-stained HCCLM3 cells were irradiated with 50 Gy, FastDCs and irradiated HCCLM3 cells were fused in 500 mL/L polyethylene glycol(PEG)+100 mL/L dimethyl sulfoxide (DMSO) to generate novel dendritomas. The FastDCs and novel dendritomas were immunostained with antiCD80, anti-CD86, anti-CD83, anti-HLA-DR mAbs and analyzed by fluorescence

  2. Late reperfusion of a totally occluded infarct-related artery increases granulocyte-colony stimulation factor and reduces stroma-derived factor-1alpha blood levels in patients with ongoing ischemia after acute myocardial infarction.

    Science.gov (United States)

    Kuo, Li-Tang; Chen, Shih-Jen; Cherng, Wen-Jin; Yang, Ning-I; Lee, Chen-Chin; Cheng, Chi-Wen; Verma, Subodh; Wang, Chao-Hung

    2009-07-01

    After acute myocardial infarction (AMI), reopening of a totally occluded infarct-related artery (IRA) at a subacute stage is still controversial in symptom-free patients. However, in patients with persistent ischemic symptoms and inadequate collaterals to the infarct area, recanalization is thought to provide beneficial effects. In addition to augmenting myocardial perfusion, we hypothesized that the benefit of recanalization involves the manipulation of circulating stem cell-mobilizing cytokines. This study included 30 patients with a totally occluded IRA and ongoing ischemic symptoms (the study group) and 30 patients with a partially occluded IRA (the control group). All patients underwent successful angioplasty and/or stenting. Before and immediately after the coronary intervention, blood granulocyte-colony-stimulating factor (G-CSF), stem-cell factor (SCF), vascular endothelial growth factor (VEGF), and stroma-derived factor-1 (SDF-1alpha) were measured. After recanalization, G-CSF levels significantly increased in the study group compared to the control group (P=0.03). SDF-1alpha levels in the study group decreased relative to the controls (P=0.02). However, no significant changes in VEGF or SCF levels between the two groups were found. In the multivariate analysis, reopening of a totally occluded IRA was independently and significantly associated with changes in G-CSF and SDF-1alpha levels after recanalization. In conclusion, our data suggest that the benefits of late reperfusion of a totally occluded IRA in patients with ongoing myocardial ischemia may involve mechanisms associated with stem cell-mobilizing and plaque-stabilizing cytokines. This study provides the rationale to investigate serial changes in cytokines and the numbers of circulating progenitors after reperfusion in the future.

  3. Bovine Peripheral Blood Monocyte Derived Dendritic Cell Culture and Identification in Vitro%奶牛外周血树突状细胞体外诱导培养与鉴定

    Institute of Scientific and Technical Information of China (English)

    詹康; 赵倩明; 隋雁南; 封飞飞; 占今舜; 赵国琦

    2016-01-01

    通过粒-巨噬细胞集落刺激因子( GM⁃CSF)和白细胞介素-4( IL⁃4)体外诱导外周血单核细胞为树突状细胞,为利用树突状细胞免疫疗法治疗奶牛乳房炎奠定基础和提供细胞模型。利用淋巴细胞分离液分离获得奶牛外周血单核细胞,在6孔板内培养2h后,弃掉含有大量的T细胞和B细胞上清液,贴壁的基本上是单核细胞,磷酸盐缓冲液清洗5次,加入含有GM⁃CSF和IL⁃4的2 mL培养基进行3 d诱导。之后,从培养基顶部小心吸弃1.4 mL的培养基,然后再补加含有GM⁃CSF和IL⁃4的1.8 mL培养基继续诱导3 d。每天通过显微镜观察细胞形态。第7天经流式检测细胞表面抗原 CD11c、CD14、主要组织相容性复合体Ⅱ( MHCⅡ)、CD40、CD80、CD86的表达。结果表明:1)第2天,一些细胞表面可以生长出刺突并伴随着伪足的生长。第3天,细胞表面的刺突和伪足越来越多。第4、5天,一些带有刺突和伪足的细胞开始聚集和融合。第6天,单核细胞基本被诱导为树突状细胞,细胞表面含有大量清晰可见的刺突和伪足。2)经流式检测,CD14、CD11c、MHCⅡ阳性表达细胞分别占诱导细胞的6.8%、65.0%、75.9%,CD80和CD86阳性表达细胞分别占诱导细胞的2.0%和1.2%。综上所述,采用奶牛外周血单核细胞经体外诱导能够获得一定纯度的奶牛树突状细胞。%This study aimed to induce bovine peripheral blood monocyte derived dendritic cell by granulocyte⁃macrophage colony stimulating factor ( GM⁃CSF) and interleukin⁃4 ( IL⁃4) cytokines, which could lay founda⁃tion and provide cell model for dairy cow mastitis treatment using cell immunotherapy. The bovine peripheral blood monocyte was acquired by lymphocyte separation medium and seeded in 6⁃proe plate to culture for 2 h. Then, suspended cells containing an amount of B and T cells were discarded, and

  4. Blood Typing

    Science.gov (United States)

    ... if you need repeated transfusions, as sickle cell anemia and thalassemia patients do. If blood transfusions are not closely ... the News Article Index About This Site Send Us Your Comments For ...

  5. Blood Disorders

    Science.gov (United States)

    ... people with blood disorders. Magnitude of the Problem Complications from deep vein thrombosis (DVT) kill more people each year than breast cancer, motor vehicle accidents, and HIV combined. Sickle cell trait ...

  6. What's Blood?

    Science.gov (United States)

    ... Rh" because scientists found it while studying Rhesus monkeys. If your blood is positive, you have this ... doctor. © 1995- The Nemours Foundation. All rights reserved. Images provided by The Nemours Foundation, iStock, Getty Images, ...

  7. Artificial blood.

    OpenAIRE

    1983-01-01

    #Blood substitutes have been developed for almost a century. The various type of artificial blood was continuously available on the market. The theme of this report is to identify the best substitute in emergency situation for some patients and science students. The definition of best is given; thus, as the vital part of the report, the comparison between them is described and discussed. Modified hemoglobin, bovine-based hemoglobin and PFCs are three basic types. In terms of the perfor...

  8. Blood Transfusion and Donation

    Science.gov (United States)

    ... receiving the blood transfusion. To keep blood safe, blood banks carefully screen donated blood. The risk of catching ... one or more times before the surgery. A blood bank will store your blood for your use. NIH: ...

  9. Blood (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Blood KidsHealth > For Parents > Blood A A A What's ... about the mysterious, life-sustaining fluid called blood. Blood Basics Two types of blood vessels carry blood ...

  10. Catecholamine blood test

    Science.gov (United States)

    Norepinephrine -- blood; Epinephrine -- blood; Adrenalin -- blood; Dopamine -- blood ... A blood sample is needed. ... the test. This is especially true if both blood and urine catecholamines are to be measured. You ...

  11. Biology of Blood

    Science.gov (United States)

    ... here for the Professional Version Home Blood Disorders Biology of Blood Overview of Blood Resources In This ... Version. DOCTORS: Click here for the Professional Version Biology of Blood Overview of Blood Components of Blood ...

  12. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... Blood Basics Blood Disorders Anemia Bleeding Disorders Blood Cancers Blood Clots Blood Clotting and Pregnancy Clots and ... Increased maternal age Other medical illness (e.g., cancer, infection) back to top How are Blood Clots ...

  13. How much blood is needed?

    Science.gov (United States)

    Seifried, E; Klueter, H; Weidmann, C; Staudenmaier, T; Schrezenmeier, H; Henschler, R; Greinacher, A; Mueller, M M

    2011-01-01

    Demographic changes in developed countries as their populations age lead to a steady increase in the consumption of standard blood components. Complex therapeutic procedures like haematopoietic stem cell transplantation, cardiovascular surgery and solid organ transplantation are options for an increasing proportion of older patients nowadays. This trend is likely to continue in coming years. On the other hand, novel aspects in transplant regimens, therapies for malignant diseases, surgical procedures and perioperative patient management have led to a moderate decrease in blood product consumption per individual procedure. The ageing of populations in developed countries, intra-society changes in the attitude towards blood donation as an important altruistic behaviour and the overall alterations in our societies will lead to a decline in regular blood donations over the next decades in many developed countries. Artificial blood substitutes or in vitro stem cell-derived blood components might also become alternatives in the future. However, such substitutes are still in early stages of development and will therefore probably not alleviate this problem within the next few years. Taken together, a declining donation rate and an increase in the consumption of blood components require novel approaches on both sides of the blood supply chain. Different blood donor groups require specific approaches and, for example, inactive or deferred donors must be re-activated. Optimal use of blood components requires even more attention.

  14. Managing your blood sugar

    Science.gov (United States)

    Hyperglycemia - control; Hypoglycemia - control; Diabetes - blood sugar control; Blood glucose - managing ... Know how to: Recognize and treat low blood sugar (hypoglycemia) Recognize and treat high blood sugar (hyperglycemia) ...

  15. 孤立性肺腺癌血流模式定量CT参数相互关系%Correlation of the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Shenjiang Li; Xiangsheng Xiao; Shiyuan Liu; Huimin Li; Chengzhou Li; Chenshi Zhang

    2007-01-01

    Objective: To evaluate the correlation of the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma (SBA). Methods: 46 patients with solitary bronchogenic adenocarcinomas (SBA) (diameter ≤ 4 cm) underwent multi-location dynamic contrast material-enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4 mL/s by using an autoinjector 90 mL, 4 × 5 mm or 4 × 2.5 mm scanning mode with stable table were performed) serial CT. Precontrast and postcontrast attenuation on every scan was recorded. Perfusion (PBA), peak height (PHBA), ratio of peak height of the SPN to that of the aorta (BA-to-A ratio) and mean transit time (MTT) were calculated. The correlation between peak height of the aorta (PHA) and parameters of the SBA (PHBA, BA-to-A ratio, PBA, and MTT) and those among parameters of the SBA were assessed by means of linear regression analysis. Regression equation among parameters of the SBA were obtain by means of stepwise regression. Results: The correlation between the SBA peak height (PHBA, 36.78 HU ± 12.02) and the aortic peak height (PHA) was significant (r = 0.506, P < 0.0001). No significant cor relation was found between the BA-to-A peak height ratio (15.33% ± 4.55) and the aortic peak height (r = 0.130, P = 0.388 >0.05) as it was between the SBA perfusion (PBA, 31.86 mL/min/100 g ± 9.74) and the aortic peak height (r = 0.049, P = 0.749 > 0.05). The SBA perfusion correlated with the PHBA and the BA-to-A peak height ratio (r = 0.394, P = 0.007 < 0.05; r = 0.407, P = 0.005 < 0.05). The PHBA correlated positively with the BA-to-A peak height ratio (r = 0.781, P < 0.0001). Mean transit time was 14.84 s ± 5.52. PBA = 18.500 + 0.872 × BA-to-A ratio. BA-to-A ratio = 4.467 + 0.295 × PHBA. Conclusion: The linear correlation between the SBA perfusion and BA-to-A ratio and that between BA-to-A ratio and PHBA can be expressed by equation.It is possible to

  16. Repair of calvarial defects with human umbilical cord blood derived mesenchymal stem cells and demineralized bone matrix in athymic rats%人脐血间充质干细胞修复颅骨缺损的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘广鹏; 李宇琳; 孙剑; 崔磊; 张文杰; 曹谊林

    2010-01-01

    Objective To investigate the feasibility of using human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) and demineralized bone matrix (DBM) scaffolds to repair critical-sized calvarial defects in athymic rats. Methods Human UCB-MSCs were isolated, expanded and osteogenically induced in vitro. Osteogenic differentiation of UCB-MSCs was evaluated by Alizarin Red staining and measurement of calcium content respectively, and then the cells were seeded onto DBM scaffolds. Bilateral full-thickness defects (5 mm in diameter) of parietal bone were created in an athymic rat model. The defects were either repaired with UCB-MSC/DBM constructs (experimental group) or with DBM scaffolds alone (control group). Animals were harvested at 6 and 12 weeks post-implantation respectively, and defect repair was evaluated with gross observation, micro-CT measurement and histological analysis. Results Micro-CT showed that new bone was formed in the experimental group at 6 weeks post-implantation, while no sign of new bone formation was observed in the control group. At 12 weeks post-transplantation, scaffolds had been degraded almost completely in both sides. It was shown that an average of (78.19±6.45)% of each defect volume had been repaired in experimental side; while in the control side, only limited bone formed at the periphery of the defect. Histological examination revealed that the defect was repaired by trabecular bone tissue in experimental side at 12 weeks, while only fibrous connection was observed in the control group. Conclusions Tissue-engineered bone composed of osteogenically-induced human UCB-MSCs on DBM scaffolds could successfully repair the critical-sized calvarial defects in athymic rat models.%目的 应用人脐血间充质干细胞(umbilical cord blood derived mesenchymal stem cells,UCB-MSCs)复合脱钙骨材料构建组织工程化骨,修复裸大鼠颅骨标准缺损.方法 体外扩增培养、成骨诱导人UCB-MSCs,采用Alizarin Red染色

  17. Blood Basics

    Science.gov (United States)

    ... of ASH ASH Meeting on Hematologic Malignancies Consultative Hematology Course ASH Meeting on Lymphoma Biology ASH Workshop on Genome Editing Publications Blood The Hematologist ASH Clinical News ASH Self-Assessment Program Hematology , ASH Education Program About Awards Membership ASH Foundation ...

  18. Blood Clots

    Science.gov (United States)

    ... of ASH ASH Meeting on Hematologic Malignancies Consultative Hematology Course ASH Meeting on Lymphoma Biology ASH Workshop on Genome Editing Publications Blood The Hematologist ASH Clinical News ASH Self-Assessment Program Hematology , ASH Education Program About Awards Membership ASH Foundation ...

  19. Blood pressure measurement

    Science.gov (United States)

    Diastolic blood pressure; Systolic blood pressure; Blood pressure reading; Measuring blood pressure ... or your health care provider will wrap the blood pressure cuff snugly around your upper arm. The lower ...

  20. Blood Count Tests

    Science.gov (United States)

    Your blood contains red blood cells (RBC), white blood cells (WBC), and platelets. Blood count tests measure the number and types of cells in your blood. This helps doctors check on your overall health. ...

  1. 体外诱导脐血单核细胞向破骨样细胞的分化%In vitro differentiation of umbilical cord blood-derived mononuclear cells towards osteoclast-like cells

    Institute of Scientific and Technical Information of China (English)

    鲍庆红; 刘文佳; 王晓荣; 周洪

    2009-01-01

    胞集落刺激因子组及1α,25-(OH)2D3+前列腺素E2组破骨样细胞数量均明显减少(F=7.46,P<0.01).结论:脐血单核细胞经骨吸收刺激因子体外诱导培养后,可分化为TRAP(+)的多核破骨样细胞,其中10-8mol/L 1α,25-(OH)2D具有最强的生物学效应.%BACKGROUND: Orthodontic tooth movement is dependent on reconstruction of periodontium. Osteoclastic bone resorption is the first step of tooth movement. The present study hotspots focus on signal transduction pathway regarding osteoclast differentiation and functional development under stress and on the relationship between periodontal ligament cells and osteoclasts. OBJECTIVE: To set up a simple method to in vitro culture human osteoclast-like cells and to observe the effects of bone resorption-stimulating factors on differentiation, proliferation, and function of osteoclast-like cells, DESIGN, TIME AND STTING: A cytological in vitro controUod observation was performed at the Central Laboratory,Stomatology Hospital, Xi'an Jiaotong University between October 2007 and May 2008. MATERIALS: Umbilical cord blood was sourced from the healthy puerperae who had not suffered from high-risk pregnancy. Freshly prepared fetal femur provided by Laboratory Animal Center, Xi'an Jiaotong University and were used for preparation of bone flaps at 100-200 μm thickness. 1α ,25-(OH)2D3, macrophage colony-stimulating factor (M-CSF), prostaglandin E2 were purchased from Sigma Company, USA.METHODS: Under aseptic condition, umbilical cord blood was collected. Following Ficoll solution separation and centrifugation, supematant was discarded. Umbilical cord blood-derived mononuclear cells were suspended with o -modified minimal essential medium (α-MEM) solution and then inoculated into a 24-well culture plate, in which, coverslips and femoral slices were pre-placed, at a density of 1×109/L, 1.0 mL per well. Five groups were set, blank control, 108 mol/L 1α ,25-(OH)2D3, 10-7 mol/L 1α ,25-(OH)2D3, macrophage colony stimulating

  2. Hemoglobin derivatives

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003371.htm Hemoglobin derivatives To use the sharing features on this page, please enable JavaScript. Hemoglobin derivatives are altered forms of hemoglobin . Hemoglobin is ...

  3. Umbelliprenin is Potentially Toxic Against the HT29, CT26, MCF-7, 4T1, A172, and GL26 Cell Lines, Potentially Harmful Against Bone Marrow-Derived Stem Cells, and Non-Toxic Against Peripheral Blood Mononuclear Cells

    Science.gov (United States)

    Rashidi, Mohsen; Ziai, Seyed Ali; Moini Zanjani, Taraneh; Khalilnezhad, Ahad; Jamshidi, Hamidreza; Amani, Davar

    2016-01-01

    Background Resistance to chemotherapy is a growing concern, thus natural anticancer agents are drawing the attention of many scientists and clinicians. One natural anticancer agent, umbelliprenin, is a coumarin produced by many species of Ferula. Objectives We aimed to examine the inhibitory effect of umbelliprenin on human and mouse bone marrow-derived stem cells (BMDSCs), peripheral blood mononuclear cells (PBMCs), and different cancer cell lines. Materials and Methods In this in vitro experimental study, the HT29, CT26, MCF-7, 4T1, A172, and GL26 cancer cells and human and mouse BMDSCs and PBMCs were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS), incubated at 37°C for 24 hours in a 5% CO2 atmosphere, and then were treated with different concentrations of umbelliprenin dissolved in dimethyl sulfoxide (DMSO) (3, 6, 12, 25, 50, 100, and 200 µg/mL) for 24, 48, and 72 hours at 37°C. Each experiment was performed in triplicate. Finally, the cell survival rate was assessed by MTT assay. The IC50 values were calculated based on the log values using GraphPad Prism version 5 software for windows (La Jolla CA, USA) and were expressed as mean ± SEM. Results Umbelliprenin inhibited the cancer cells in a concentration-dependent (P 0.05). The most sensitive and resistant cell lines at the 24-hour incubation time were 4T1 (IC50, 30.9 ± 3.1 µg/mL) and A172 (IC50, 51.9 ± 6.7 µg/mL); at the 48-hour incubation time: 4T1 (IC50, 30.6 ± 2.6 µg/mL) and CT26 (IC50, 53.2 ± 3.6 µg/mL); and at the 72-hour incubation time: HT29 (IC50, 37.1 ± 1.4 µg/mL) and 4T1 (IC50, 62.2 ± 4.8 µg/mL). Both human and mouse BMDSCs showed the highest resistance at the 24-hour incubation time (IC50s, 254.7 ± 21 and 204.4 ± 4.5 µg/mL, respectively) and the highest sensitivity at the 72-hour incubation time (IC50s, 120.4 ± 5 and 159.0 ± 7.3 µg/mL, respectively). The PBMCs of both human and mouse origin revealed very strong resistance to the studied

  4. 沙棘叶提取物抗登革病毒的实验研究%Effect of Hippophae rhamnoides Leaf Extract Against Dengue Virus Infection in Human Blood-derived Macrophages

    Institute of Scientific and Technical Information of China (English)

    花圣卓; 李铂岩

    2012-01-01

    Dengue virus occurs as four distinct serotypes,called Dengue 1,2,3,and 4.Symptomaticdengue virus infection ranges from a self limited febrile illness,dengue fever(DF),to a more severedisease,dengue hemorrhagic fever/dengue shock syndrome(DHF/DSS).The anti-Dengue treatmentis severely hampered as no specific therapeutic agents are available.Even present treatmentstrategies for Dengue are more supportive than curative.In the present study anti-dengue activity of Hippoplzae rhamnoides{Seabuckthorn,SBT)leaf extract 4vas evaluated in Dengue virus type-2 infected blood-derived human macrophages as macrophages are the primary target of Denguevirus infection.Infected cells were treated with SBT leaf extract and compared with commerciallyavailable anti-viral drug,Ribavirin.The extract was able to maintain the cell viability of Dengue-infected cells at par with Ribavirin along with the decrease and increase in TNF-[alpha]and IFN-[gamma]respectively.Anti-dengue activity of SBT extract was further determined by the traditionalplaque assay.These observations suggest that the SBT leaf extract has a significant anti-dengueactivity and has the potential for the treatment of Dengue.%登革病毒依抗原性不同,可分为1、2、3、4四个血清型。它除了能导致一定范围内发热的典型登革热外,还能引致更严重的登革出血热和登革休克综合症。由于没有具体有效的治疗药物,目前尚无好的治疗登革热的方法,治疗方案多是支持性的。本实验评估了在2型登革病毒感染的人血源性巨噬细胞中沙棘叶提取物的抗登革病毒活性,选择巨噬细胞的原因是因为巨噬细胞是登革病毒感染的首要目标。受感染的细胞用沙棘叶提取物治疗并与市售的抗病毒药物利巴韦林作比较,研究发现沙棘叶提取物维持登革病毒感染细胞活力的能力几乎等同于利巴韦林。传统的空斑试验进一步确定了沙棘叶提取物的抗登革病毒活性。

  5. In vitro culture and influencing factors of mesenchymal stem cells derived from human umbilical blood%人脐带血间充质干细胞的体外培养及其影响因素

    Institute of Scientific and Technical Information of China (English)

    黄伟; 祝建中; 苗宗宁; 王玲; 王新

    2007-01-01

    验总共培养和分析了70例脐血间充质干细胞样本.由于10例予含高糖的培养基培养的标本均未获得理想的间充质干细胞,故未进行统计学分析.①按照本实验所建立的培养体系,约20%的样本成功培养出脐血间充质干细胞.原代细胞在培养2周后可达到融合,一般其倍增时间为3~4 d,传代后7~8 d即可达到融合.②扩增至第5代的间充质干细胞结果显示,脐血间充质干细胞均一稳定地表达间充质干细胞相关的抗原标记:CD29,CD44,CD105,但不表达CD34,CD45,CD106,HLA-DR,这与源于骨髓的间充质干细胞的表面抗原标记相一致.③血清包被组间充质干细胞贴壁率显著高于无血清包被组(P<0.01).结论:脐带血中的间充质干细胞可在体外培养、扩增,能够作为间充质干细胞的一种有效来源.高糖可能抑制人脐血间充质干细胞的生长和扩增.%BACKGROUND: Multipotential mesenchymal stem cells (MSCs) can be differentiated into bone, fat, cartilage, muscle and endothelial cell at the specific conditions, so it draws great attentions of the related study.OBJ ECTTVE: To establish the method of in vitro culture and expansion of human umbilical blood-derived MSCs and investigate their influencing factors.DESTGN: Randomized and controlled trials.SETTING: Department of Tissue Engineering and Cell Biology in Wuxi Third People's Hospital.MATERTALS: Seventy cases of human umbilical cord blood (HUCB) of healthy neonates (selected from Parturient Room, Department of Gynecology and Obstetrics, Wuxi Third People's Hospital, with the informed consents of the puerpera and their relatives), 40 mL each; dulbecco's minimal essential medium (DMEM) of low glucose (LG) at the dose of 50 g/L, fetal bovine serum (FBS), mycillin and trypsin (all were from Gibco), FITC-labeled mice anti-human CD29, CD105 and CD106 (Ancell) monoclonal fluorescent antibody, PE-labeled mice anti-human CD34, CD44, CD45, CD19, HLA-DR (Immunotech)monoclonal fluorescent antibody

  6. 人脐血干细胞体外诱导为肥大细胞的研究进展%Mast cells derived from stem cells of umbilical cord blood

    Institute of Scientific and Technical Information of China (English)

    王海燕; 何韶衡

    2005-01-01

    Mast cells (MCs) play a key role in the pathogenesis of allergic diseases. Tissue MCs are originated from hematopoiefic stem cells in bone marrow. In recent years, it was reported that human mast cells could be differentiated from stem cells of umbilical cord blood. In this review, we summarize the development in this novel area.

  7. Low Blood Glucose (Hypoglycemia)

    Science.gov (United States)

    ... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Low Blood Glucose (Hypoglycemia) What is hypoglycemia? Hypoglycemia, also called low blood glucose or low blood sugar, occurs when ...

  8. Financial Derivatives

    DEFF Research Database (Denmark)

    Wigan, Duncan

    2013-01-01

    Contemporary derivatives mark the development of capital and constitute a novel form of ownership. By reconfiguring the temporal, spatial and legal character of ownership derivatives present a substantive challenge to the tax collecting state. While fiscal systems are nationally bounded and inheren...... and inherently static, capital itself is unprecedentedly mobile, fluid and fungible. As such derivatives raise the specter of ‘financial weapons of mass destruction’....

  9. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... Initiative Research Programs and Awards View all Blood Current Issue First Edition Abstracts Blood Advances A peer- ... Get email updates View all meetings Publications Blood Current Issue First Edition Abstracts Blood Advances A peer- ...

  10. Hypertension (High Blood Pressure)

    Science.gov (United States)

    ... Surgery? A Week of Healthy Breakfasts Shyness Hypertension (High Blood Pressure) KidsHealth > For Teens > Hypertension (High Blood Pressure) Print ... rest temperature diet emotions posture medicines Why Is High Blood Pressure Bad? High blood pressure means a person's heart ...

  11. White Blood Cell Count

    Science.gov (United States)

    ... limited. Home Visit Global Sites Search Help? White Blood Cell Count Share this page: Was this page helpful? ... Count; Leukocyte Count; White Count Formal name: White Blood Cell Count Related tests: Complete Blood Count , Blood Smear , ...

  12. Lead levels - blood

    Science.gov (United States)

    Blood lead levels ... A blood sample is needed. Most of the time blood is drawn from a vein located on the inside ... may be used to puncture the skin. The blood collects in a small glass tube called a ...

  13. Blood donation before surgery

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000367.htm Blood donation before surgery To use the sharing features on ... described here. Blood From the Public (Volunteer Blood Donation) The most common source of blood given during ...

  14. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... infection) back to top How are Blood Clots in Pregnant Women Treated? Typically, blood clots are treated ... history of blood clots or blood clotting disorders in your family. Remain active, with your doctor's approval. ...

  15. High Blood Cholesterol

    Science.gov (United States)

    ... version of this page please turn Javascript on. High Blood Cholesterol What is High Blood Cholesterol? What is Cholesterol? Cholesterol is a ... heart disease. If Your Blood Cholesterol Is Too High Too much cholesterol in your blood is called ...

  16. Low Blood Pressure

    Science.gov (United States)

    ... a problem. Sometimes blood pressure that is too low can also cause problems. Blood pressure is the ... reading is 90/60 or lower, you have low blood pressure. Some people have low blood pressure ...

  17. Blood Transfusion (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Blood Transfusions KidsHealth > For Parents > Blood Transfusions A A ... and help put your child at ease. About Blood Transfusions Blood is like the body's transportation system. ...

  18. Polydopamine/dialdehyde starch/chitosan composite coating for in-tube solid-phase microextraction and in-situ derivation to analysis of two liver cancer biomarkers in human blood.

    Science.gov (United States)

    Wu, Shiju; Cai, Cuicui; Cheng, Jing; Cheng, Min; Zhou, Hongbin; Deng, Jiali

    2016-09-01

    In order to highly enrich two liver cancer biomarkers (hexanal and 2-butanone) in human blood, in this study, natural nontoxic polydopamine/dialdehyde starch/chitosan (PD/DAS/CHI) coating material was synthesized and immobilized on the inner wall of polytetrafluoro-ethlyene (PTFE) tube. It was used to develop the method based on in-tube solid-phase microextraction (IT-SPME) with in-situ derivatization (ISD) coupled to high performance liquid chromatography for the determination of the above mentioned two liver cancer biomarkers in human blood. The simple, rapid and sensitive IT-SPME-ISD method can be finished within 11 min. Under optimum conditions, the limits of detection (LODs) were 1.4 and 1.6 nmol L(-1) for hexanal and 2-butanone, respectively. The relative recoveries from real human blood samples were in the range from 70% to 91% with the intra- and inter-day precisions less than 7.2%. Furthermore, this method was successfully applied for the analysis of hexanal and 2-butanone in blood samples from healthy people with 0.42 ± 0.05 and 0.34 ± 0.04 μmol L(-1), while liver cancer patients with 1.90 ± 0.07  μmol L(-1) and 0.91 ± 0.07 μmol L(-1), respectively. The t-test's results showed there is a statistically significant difference between the data from healthy persons and liver cancer patients. Hence, the developed method might be applied in the screening of suspected liver cancer patients.

  19. Effective Action Distance of Co-Culture between Umbilical Cord Blood-Derived Hematopoietic Stem/Progenitor Cells and Human Adipose Derived Stem Cells%脐血造血干/祖细胞与脂肪干细胞共培养的作用距离研究

    Institute of Scientific and Technical Information of China (English)

    宋克东; 崔占峰; 刘天庆; 武爽; 郭文华; 郝永杰; 方美云; 石芳鑫; 朱丽丽; 马学虎

    2011-01-01

    设计了一种细胞间距可调的transwell共培养方法,以研究脐带血来源的造血干/祖细胞(HS/PCs)和人脂肪干细胞(human-adipose derived stem cells,h-ADSCs)体外共培养时细胞间作用距离对造血干细胞扩增能力和脂肪干细胞在共培养后干细胞特性的影响.采用不同规格的砂纸打磨孔板的上壁面,经高精度游标卡尺测量,使两种细胞之间的有效接触间距为10~450 μm不等.然后以h-ADSCs为基质细胞,分别考察HS/PCs和h-ADSCs在不同的作用距离下的共培养情况.其间每24小时对细胞进行计数,观察细胞形态.培养7天后对MNCs表面抗原CD34+、CFU-GM集落扩增倍数进行了检测;同时也对h-ADSCs表面抗原(CD13、CD29、CD34、CD44、CD45、CD73、CD105、CD166、HLA-DR)及其多向分化潜能(成骨、成软骨、成脂肪)进行分析以鉴定其干细胞性能.结果表明,通过transwell共培养,细胞之间在作用距离为350μm时HS/PCs的扩增效果最好,其中造血MNCs扩增了15.1±0.2倍,CD34+扩增了5.0±0.1倍;扩增的h-ADSCs表达CD29、CD44、CD166,而不表达CD34、CD45,且在适当诱导条件下可以向成骨细胞、软骨细胞、脂肪细胞分化.%In order to investigate the effects of in vitro co-culture distance between umbilical cord blood-derived hematopoietic stem/progenitor cells (HS/PCs) and human adipose derived stem cells (h-ADSCs) on the expansion of HS/PCs and the stem cell properties of h-ADSCs, a novel transwell co-culture protocol in which the distance between the two culture chambers could be adjusted was designed. Sand papers with different specifications were utilized to adjust the cellular action distance between two kinds of cells mentioned above in the range of 10 to 450 μrn which was measured by a high-precision vernier caliper. Then the HS/PCs were cultured in the modified transwell supported by ADSCs for 7 days. The total cell number was counted by using a hemacytometer and the cell morphology

  20. A novel, rapid strategy to form dendritomas from human dendritic cells and hepatocellular carcinoma cell line HCCLM3 cells using mature dendritic cells derived from human peripheral blood CD14+ monocytes within 48 hours of in vitro culture

    OpenAIRE

    Guan, Xin; Peng, Ji-Run; Yuan, Lan; Wang, Hui; Wei, Yu-Hua; Leng, Xi-Sheng

    2004-01-01

    AIM: Dendritomas formed by fusing cancer cells to dendritic cells have already been applied to clinical treatment trial of several types of cancers. Dendritic cells for the fusion in most trials and experiments were from blood monocytes in standard 7-d protocol culture, which requires 5-7 d of culture with granulocyte-macrophage–colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), followed by 2-3 d of activation with a combination of proinflammatory mediators such as tumor necrosis fa...

  1. Derivative Chameleons

    CERN Document Server

    Noller, Johannes

    2012-01-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field \\phi, but also of its derivatives via higher order co-ordinate invariants. Specifically we consider the first such non-trivial conformal factor A(\\phi,X), where X is the canonical kinetic term for \\phi. The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for \\phi. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning...

  2. Application of CART Algorithm in Blood Donors Classification

    Directory of Open Access Journals (Sweden)

    T. Santhanam

    2010-01-01

    Full Text Available Problem statement: This study used data mining modeling techniques to examine the blood donor classification. The availability of blood in blood banks is a critical and important aspect in a healthcare system. Blood banks (in the developing countries context are typically based on a healthy person voluntarily donating blood and is used for transfusions or made into medications. The ability to identify regular blood donors will enable blood banks and voluntary organizations to plan systematically for organizing blood donation camps in an effective manner. Approach: Identify the blood donation behavior using the classification algorithms of data mining. The analysis had been carried out using a standard blood transfusion dataset and using the CART decision tree algorithm implemented in Weka. Results: Numerical experimental results on the UCI ML blood transfusion data with the enhancements helped to identify donor classification. Conclusion: The CART derived model along with the extended definition for identifying regular voluntary donors provided a good classification accuracy based model.

  3. Derivative chameleons

    Science.gov (United States)

    Noller, Johannes

    2012-07-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field phi, but also of its derivatives via higher order co-ordinate invariants (such as ∂μphi∂μphi,squphi,...). Specifically we consider the first such non-trivial conformal factor A(phi,∂μphi∂μphi). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for phi → phi+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type.

  4. Imatinib triggers mesenchymal-like conversion of CML cells associated with increased aggressiveness

    Institute of Scientific and Technical Information of China (English)

    Alexandre Puissant; Yann Chéli; Jill-Patrice Cassuto; Sophie Raynaud; Laurence Legros; Jean-Max Pasquet; Francois-Xavier Mahon; Frédéric Luciano; Patrick Auberger; Maeva Dufies; Nina Fenouille; Issam Ben Sahra; Arnaud Jacquel; Guillaume Robert; Thomas Cluzeau; Marcel Deckert; Mélanie Tichet

    2012-01-01

    Chronic myelogenous leukemia (CML) is a cytogenetic disorder resulting from the expression of p210BCR-ABL Imatinib,an inhibitor of BCR-ABL,has emerged as the leading compound to treat CML patients.Despite encouraging clinical results,resistance to imatinib represents a major drawback for therapy,as a substantial proportion of patients are refractory to this treatment.Recent publications have described the existence of a small cancer cell population with the potential to exhibit the phenotypic switch responsible for chemoresistance.To investigate the existence of such a chemoresistant cellular subpopulation in CML,we used a two-step approach of pulse and continuous selection by imatinib in different CML cell lines that allowed the emergence of a subpopulation of adherent cells (IM-R Adh) displaying an epithelial-mesenchymal transition (EMT)-like phenotype.Overexpression of several EMT markers was observed in this CML subpopulation,as well as in CD34+ CML primary cells from patients who responded poorly to imatinib treatment.In response to imatinib,this CD44high/CD24low IM-R Adh subpopulation exhibited increased adhesion,transmigration and invasion in vitro and in vivo through specific overexpression of the αVβ3 receptor.FAK/Akt pathway activation following integrin β3 (ITGβ3) engagement mediated the migration and invasion of IM-R Adh cells,whereas persistent activation of ERK counteracted BCR-ABL inhibition by imatinib,promoting cell adhesion-mediated resistance.

  5. Global Derivatives

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    ." - Steen Parsholt, Chairman and CEO, Aon Nordic Region. "Andersen has done a wonderful job of developing a comprehensive text that deals with risk management in global markets. I would recommend this book to any student or businessman who has a need to better understand the risks and risk management...... management practice. Of particular note is the global and integrated approach chosen in this book which should be of special interest to aspiring managers active in global and international markets." - Dr Jean-Pierre Zigrand, Lecturer in Finance, London School of Economics, UK. More than 90 per cent...... management situations. Its key features include: derivatives are introduced in a global market perspective; describes major derivative pricing models for practical use, extending these principles to valuation of real options; practical applications of derivative instruments are richly illustrated...

  6. Electricity derivatives

    CERN Document Server

    Aïd, René

    2015-01-01

    Offering a concise but complete survey of the common features of the microstructure of electricity markets, this book describes the state of the art in the different proposed electricity price models for pricing derivatives and in the numerical methods used to price and hedge the most prominent derivatives in electricity markets, namely power plants and swings. The mathematical content of the book has intentionally been made light in order to concentrate on the main subject matter, avoiding fastidious computations. Wherever possible, the models are illustrated by diagrams. The book should allow prospective researchers in the field of electricity derivatives to focus on the actual difficulties associated with the subject. It should also offer a brief but exhaustive overview of the latest techniques used by financial engineers in energy utilities and energy trading desks.

  7. Blood vessels, circulation and blood pressure.

    Science.gov (United States)

    Hendry, Charles; Farley, Alistair; McLafferty, Ella

    This article, which forms part of the life sciences series, describes the vessels of the body's blood and lymphatic circulatory systems. Blood pressure and its regulatory systems are examined. The causes and management of hypertension are also explored. It is important that nurses and other healthcare professionals understand the various mechanisms involved in the regulation of blood pressure to prevent high blood pressure or ameliorate its damaging consequences.

  8. Pancreatic islet blood flow and its measurement.

    Science.gov (United States)

    Jansson, Leif; Barbu, Andreea; Bodin, Birgitta; Drott, Carl Johan; Espes, Daniel; Gao, Xiang; Grapensparr, Liza; Källskog, Örjan; Lau, Joey; Liljebäck, Hanna; Palm, Fredrik; Quach, My; Sandberg, Monica; Strömberg, Victoria; Ullsten, Sara; Carlsson, Per-Ola

    2016-05-01

    Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting β-cells, endothelium-derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future.

  9. 人胰岛素样生长因子1基因质粒载体的构建及其在人脐血源性神经干细胞中的表达%Construction of Plasmid Vector Containing Human Insulin-Like Growth Factor 1 and Its Expression in Human Umbilical Cord Blood-Derived Neural Stem Cells

    Institute of Scientific and Technical Information of China (English)

    王军; 吴值荣; 朱登纳; 高峰; 侯艳艳; 陈海; 王留霞

    2011-01-01

    Objective To construct the plasmid expression vector containing human insulin - like growth factor 1 ( IGF - 1 ), and examine the expression of IGF - 1 gene in human umbilical cord blood - derived neural stem cells(NSCs).Methods The IGF - 1 gene was extracted from the fetal liver via reverse tranacription polymerase chain reaction( RT - PCR) ,then the product of PCR and plasmid pcDNA3.1 were purified by gel extraction.After enzyme digestion of DNA restriction enzyme - BamH Ⅰ and Hind Ⅲ, purified IGF - 1 gene was cloned into expression plasmid vector pcDNA3.1 by T4 DNA Ligase.Recombinant plasmid was identified by DNA sequencing method and enzyme digestion of DNA restriction enzyme - BamH Ⅰ and Hind Ⅲ.Recombinant pcDNA3.1 - IGF - 1 and empty plasmid were transfected into human umbilical cord blood - derived NSCs through lipofectin transfection.After transfection, transfected umbilical cord blood - derived NSCs were filtered with neomycin( G418 ).The expression of IGF - 1 gene in the gene transfected umbilical cord blood - derived was examined by immunocytochemical method and RT - PCR.Results IGF - 1 gene was successfully extracted from the fetal liver.Recombinants peDNA3.1 -IGF - 1 was proved accurate by restriction enzyme digestion and sequencing.Recombinant was transfected into human umbilical cord blood -derived NSCs by liposome for 24 hours,then selection cell clones appeared after 2 weeks for G418 filtering.In umbilical cord blood -derived NSCs transfected by recombinant plasmid vector, the expression of IGF- 1 gene was successful, which was detected by immtmocyto-chemical method and the expression of IGF - 1 mRNA was also positive while the other was negative compared with controla,which was examined by RT - PCR.Conclusion IGF - 1 gene can expressed in umbilical cord blood - derived NSCs transfected by recombinant plasmid vector.%目的 构建人胰岛素样生长因子1(IGF-1)质粒表达载体,并观察重组体pcDNA3.1-IGF-1转染后的脐血

  10. Blood Culture (For Parents)

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old Blood Culture KidsHealth > For Parents > Blood Culture Print A A ... adjust the treatment choice. Why Do a Blood Culture? During some illnesses, certain infection-causing bacteria and ...

  11. Coughing up blood

    Science.gov (United States)

    ... gastrointestinal tract. Blood that comes up with a cough often looks bubbly because it is mixed with ... conditions, diseases, and medical tests may make you cough up blood. These include: Blood clot in the ...

  12. High Blood Pressure

    Science.gov (United States)

    ... normal blood pressure 140/90 or higher is high blood pressure Between 120 and 139 for the top number, ... prehypertension. Prehypertension means you may end up with high blood pressure, unless you take steps to prevent it. High ...

  13. High Blood Pressure (Hypertension)

    Science.gov (United States)

    ... Print Page Text Size: A A A Listen High Blood Pressure (Hypertension) Nearly 1 in 3 American adults has ... weight. How Will I Know if I Have High Blood Pressure? High blood pressure is a silent problem — you ...

  14. What Is Blood?

    Science.gov (United States)

    ... Foundation for America's Blood Centers ADRP What is blood? PUBLICATIONS EDUCATION PRESS ROOM BLOG CAREERS CONTACT ABC ... for patients who need it. One unit of blood can be separated into the following components: Nearly ...

  15. Ketones blood test

    Science.gov (United States)

    ... Ketones - serum; Nitroprusside test; Ketone bodies - serum; Ketones - blood ... A blood sample is needed. ... When the needle is inserted to draw blood, some people feel slight ... there may be some throbbing or a slight bruise. This soon ...

  16. Magnesium blood test

    Science.gov (United States)

    Magnesium - blood ... A blood sample is needed. ... When the needle is inserted to draw blood, some people feel slight pain. Others feel a prick or stinging. Afterward, there may be some throbbing or a slight bruise. This soon ...

  17. CEA blood test

    Science.gov (United States)

    Carcinoembryonic antigen blood test ... A blood sample is needed . ... When the needle is inserted to draw blood, some people feel moderate pain. Others feel only a prick or stinging sensation. Afterward, there may be some throbbing or a slight bruise. ...

  18. Glucagon blood test

    Science.gov (United States)

    ... type I - glucagon test; Hypoglycemia - glucagon test; Low blood sugar - glucagon test ... A blood sample is needed . ... When the needle is inserted to draw blood, some people feel ... Afterward, there may be some throbbing or a slight bruise. This ...

  19. Special Blood Donation Procedures

    Science.gov (United States)

    ... takes about 10 minutes. Double red blood cell donation In the so-called double red blood cell ... can be cured with apheresis. Directed or designated donation Family members or friends can donate blood specifically ...

  20. Home blood sugar testing

    Science.gov (United States)

    Diabetes - home glucose testing; Diabetes - home blood sugar testing ... Usual times to test your blood sugar are before meals and at bedtime. Your provider may ask you to check your blood sugar 2 hours after a meal. Ask ...

  1. High blood sugar

    Science.gov (United States)

    ... High blood glucose - self-care; Diabetes - high blood sugar ... Symptoms of high blood sugar can include: Being very thirsty or having a dry mouth Having blurry vision Having dry skin Feeling weak or tired ...

  2. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  3. Blood and Diversity

    Science.gov (United States)

    ... patient diversity. For example, U-negative and Duffy-negative blood types are unique to the African-American community. ... most common blood type and because type O negative blood, in particular, is the universal type needed for ...

  4. Blood Pressure Test

    Science.gov (United States)

    ... an online personal health record or blood pressure tracker, for example. This gives you the option of ... lower your blood pressure. Exercise regularly. Regular physical activity can help lower your blood pressure and keep ...

  5. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... First Edition Abstracts Blood Advances A peer-reviewed, online only, open access journal with a unique focus ... help: Results of Clinical Studies Published in Blood Search Blood , the official journal of ASH, for the ...

  6. Symptoms of Blood Disorders

    Science.gov (United States)

    ... leg (causing most often swelling, redness, and/or warmth of the leg or shortness of breath) Petechiae ( ... Disorders Symptoms of Blood Disorders Medical History and Physical Examination for Blood Disorders Laboratory Tests for Blood ...

  7. Low Blood Pressure (Hypotension)

    Science.gov (United States)

    ... and rises sharply on waking. Blood pressure: How low can you go? What's considered low blood pressure ... even life-threatening disorders. Conditions that can cause low blood pressure Some medical conditions can cause low ...

  8. Red blood cell production

    Science.gov (United States)

    ... to one part of the body or another. Red blood cells are an important element of blood. Their job ... is carried to and eliminated by the lungs. Red blood cells are formed in the red bone marrow of ...

  9. Money for Blood and Markets for Blood.

    Science.gov (United States)

    Derpmann, Simon; Quante, Michael

    2015-12-01

    Ontario's Bill 178 proposing a Voluntary Blood Donations Act declares the offer or acceptance of payment for the donation of blood a legal offence and makes it subject to penalty. The bill reinvigorates a fundamental debate about the ethical problems associated with the payment of money for blood. Scarcity of blood donors is a recurring problem in most health systems, and monetary remuneration of the willingness to donate blood is regularly discussed--and sometimes practiced--as a means to overcome scarcity in blood. However, making blood an object of economic exchange has long aroused ethical concerns that often refer to the specific meaning of blood. From the perspective of a modern understanding of money as a metric of economic value, the exchange of money for blood--shed or given--is seen as ethically troubling, because it appears to imply a commensurability of the value of human life and economic wealth. In this paper, we begin with a general taxonomy of the types of arguments that speak in favour or against compensating donors for giving blood. We then describe the context in which the discussion about payment for blood arises, and of the specific aims and concerns that are brought forward in this context. This is used to reconstruct the normative background that supports the rejection of payment for blood as it is envisaged in Bill 178 and the aims of the proposal. We then argue that while a payment indeed changes the nature of a blood donation in an ethically considerable way, we do not believe that decisive arguments against the monetary remuneration of blood donations can be substantiated, at least not independently of assuming specific societal circumstances. Thus it may be possible to establish a stable and safe blood supply through just gratification while at the same time taking strong provisions against social disconnection, injustice, exploitation or heteronomy.

  10. Synthesis and initial evaluation of YM-08, a blood-brain barrier permeable derivative of the heat shock protein 70 (Hsp70) inhibitor MKT-077, which reduces tau levels.

    Science.gov (United States)

    Miyata, Yoshinari; Li, Xiaokai; Lee, Hsiu-Fang; Jinwal, Umesh K; Srinivasan, Sharan R; Seguin, Sandlin P; Young, Zapporah T; Brodsky, Jeffrey L; Dickey, Chad A; Sun, Duxin; Gestwicki, Jason E

    2013-06-19

    The molecular chaperone, heat shock protein 70 (Hsp70), is an emerging drug target for treating neurodegenerative tauopathies. We recently found that one promising Hsp70 inhibitor, MKT-077, reduces tau levels in cellular models. However, MKT-077 does not penetrate the blood-brain barrier (BBB), limiting its use as either a clinical candidate or probe for exploring Hsp70 as a drug target in the central nervous system (CNS). We hypothesized that replacing the cationic pyridinium moiety in MKT-077 with a neutral pyridine might improve its clogP and enhance its BBB penetrance. To test this idea, we designed and synthesized YM-08, a neutral analogue of MKT-077. Like the parent compound, YM-08 bound to Hsp70 in vitro and reduced phosphorylated tau levels in cultured brain slices. Pharmacokinetic evaluation in CD1 mice showed that YM-08 crossed the BBB and maintained a brain/plasma (B/P) value of ∼0.25 for at least 18 h. Together, these studies suggest that YM-08 is a promising scaffold for the development of Hsp70 inhibitors suitable for use in the CNS.

  11. Experimental Study on Tissue Engineered Small-Diameter Blood Vessel Walls Using Adipose Derived Stem Cells%应用脂肪干细胞构建组织工程化小口径血管平滑肌层的实验研究

    Institute of Scientific and Technical Information of China (English)

    王琛; 郭芳芳; 张昀; 巩伦礼; 崔磊

    2012-01-01

    Objective To investigate the feasibility of constructing tissue engineered blood vessel walls in bioreactor using adipose derived stem cells. Methods Adipose derived stem cells (ADSCs) were obtained from fresh human lipoaspirates, and under the induction of TGF-31 and BMP4, hADSCs were differentiated into smooth muscle cells, and then the differentiated hADSCs were collected and seeded onto PGA mesh to form cell-PGA constructs. Thereafter, the cell/PGA constructs were cultivated in a bioreactor with the pulsatile radial stress (pulse rate: 75/min, radical distension <5%) for 8 weeks. New small diameter blood vessel walls was formed, the constructs were examined histologically and biomechanically and compared with normal blood vessels. Results With induction of TGF-β1 and BMP4 together, hADSCs acquired a SMC morphology, and grew in a "hill and valley" pattern similar to what was observed in primary isolated hUASMCs, with the expression of smooth muscle-specific contractile proteins including α- SMA, SM22α, calponin, and SM-MHC. An elastic small diameter vessel wall (4 mm in diameter) with improved biomechanical strength and well-organized collagenous fibers were engineered by in vitro culture of SMC -differentiated hADSCs on the PGA scaffold in a blood vessel bioreactor. Conclusion hADSCs can serve as a new cell source for SMCs in blood vessel engineering, and an elastic small diameter vessel wall could be engineered in a bioreactor. It is a promising candidate for treating cardiovascular diseases and for blood vessel engineering purposes.%目的 探索利用脂肪干细胞在生物反应器内构建组织工程血管平滑肌层的可行性.方法 用抽吸的脂肪获取脂肪干细胞,在生长因子TGF-β1和BMP4作用下诱导成平滑肌细胞,然后将诱导的平滑肌细胞接种于PGA上,将细胞-材料复合物置于生物反应器内进行培养,在模拟胚胎发育血流动力学的刺激下(搏动频率:75次/分;扩展量<5%),构建小口径

  12. Treating High Blood Pressure

    Science.gov (United States)

    About High Blood Pressure Many people in the United States die from high blood pressure. This condition usually does not cause symptoms. Most ... until it is too late. A person has high blood pressure when the blood pushes against Visit your doctor ...

  13. Hypertension (High Blood Pressure)

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Hypertension (High Blood Pressure) KidsHealth > For Teens > Hypertension (High Blood Pressure) A ... rest temperature diet emotions posture medicines Why Is High Blood Pressure Bad? High blood pressure means a person's heart ...

  14. BUN - blood test

    Science.gov (United States)

    Blood urea nitrogen ... A blood sample is needed. Most of the time blood is drawn from a vein located on the inside ... Many medicines can interfere with blood test results. Your health ... if you need to stop taking any medicines before you have this ...

  15. Blood lead levels and chronic blood loss

    Energy Technology Data Exchange (ETDEWEB)

    Manci, E.A.; Cabaniss, M.L.; Boerth, R.C.; Blackburn, W.R.

    1986-03-01

    Over 90% of lead in blood is bound to the erythrocytes. This high affinity of lead for red cells may mean that chronic blood loss is a significant means for excretion of lead. This study sought correlations between blood lead levels and clinical conditions involving chronic blood loss. During May, June and July, 146 patients with normal hematocrits and red cell indices were identified from the hospital and clinic populations. For each patient, age, race, sex and medical history were noted, and a whole blood sample was analyzed by flameless atomic absorption spectrophotometry. Age-and race-matched pairs showed a significant correlation of chronic blood loss with lead levels. Patients with the longest history of blood loss (menstruating women) had the lowest level (mean 6.13 ..mu..g/dl, range 3.6-10.3 ..mu..g/dl). Post-menopausal women had levels (7.29 ..mu..g/dl, 1.2-14 ..mu..g/dl) comparable to men with peptic ulcer disease, or colon carcinoma (7.31 ..mu..g/dl, 5.3-8.6 ..mu..g/dl). The highest levels were among men who had no history of bleeding problems (12.39 ..mu..g/dl, 2.08-39.35 ..mu..g/dl). Chronic blood loss may be a major factor responsible for sexual differences in blood lead levels. Since tissue deposition of environmental pollutants is implicated in diseases, menstruation may represent a survival advantage for women.

  16. Transcutaneous measurement of volume blood flow

    Science.gov (United States)

    Daigle, R. E.; Mcleod, F. D.; Miller, C. W.; Histand, M. B.; Wells, M. K.

    1974-01-01

    Blood flow velocity measurements, using Doppler velocimeter, are described. The ability to measure blood velocity using ultrasound is derived from the Doppler effect; the change in frequency which occurs when sound is reflected or transmitted from a moving target. When ultrasound of the appropriate frequency is transmitted through a moving blood stream, the blood cells act as point scatterers of ultrasonic energy. If this scattered ultrasonic energy is detected, it is found to be shifted in frequency according to the velocity of the blood cells, nu, the frequency of the incident sound, f sub o, the speed of sound in the medium, c, and the angle between the sound beam and the velocity vector, o. The relation describing this effect is known as the Doppler equation. Delta f = 2 f sub o x nu x cos alpha/c. The theoretical and experimental methods are evaluated.

  17. Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces.

    Science.gov (United States)

    Caley, Matthew P; King, Helen; Shah, Neel; Wang, Kai; Rodriguez-Teja, Mercedes; Gronau, Julian H; Waxman, Jonathan; Sturge, Justin

    2016-02-01

    The diverse composition and structure of extracellular matrix (ECM) interfaces encountered by tumor cells at secondary tissue sites can influence metastatic progression. Extensive in vitro and in vivo data has confirmed that metastasizing tumor cells can adopt different migratory modes in response to their microenvironment. Here we present a model that uses human stromal cell-derived matrices to demonstrate that plasticity in tumor cell movement is controlled by the tumor-associated collagen receptor Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) and the crosslinking of collagen fibers by stromal-derived lysyl oxidase (LOX). Human osteoblast-derived and fibroblast-derived ECM supported a rounded 'amoeboid-like' mode of cell migration and enhanced Endo180 expression in three prostate cancer cell lines (PC3, VCaP, DU145). Genetic silencing of Endo180 reverted PC3 cells from their rounded mode of migration towards a bipolar 'mesenchymal-like' mode of migration and blocked their translocation on human fibroblast-derived and osteoblast-derived matrices. The concomitant decrease in PC3 cell migration and increase in Endo180 expression induced by stromal LOX inhibition indicates that the Endo180-dependent rounded mode of prostate cancer cell migration requires ECM crosslinking. In conclusion, this study introduces a realistic in vitro model for the study of metastatic prostate cancer cell plasticity and pinpoints the cooperation between tumor-associated Endo180 and the stiff microenvironment imposed by stromal-derived LOX as a potential target for limiting metastatic progression in prostate cancer.

  18. Blood and cerebrospinal fluid levels of brain-derived neurotrophic factor in patients with hypertensive cerebral hemorrhage and their correlation with recovery of neurological functions%高血压脑出血患者脑源性神经营养因子水平变化及其与神经功能的相关性研究

    Institute of Scientific and Technical Information of China (English)

    陈胜利; 龚涛; 李长清; 张书琼; 李莉

    2011-01-01

    Brain-derived neurotropic factor (BDNF) contents in blood and cerebrospinal fluid (CSF) were detected by ELISA method in 30 cases of hypertensive cerebral hemorrhage (HCH group) and 30 healthy subjects (control group).The performance and neurological functions of patients were evaluated by National Institutes of Health Stroke Scale( NIHSS),Hamilton Depression Scale ( HAMD),Barthel Index of Daily Living Skills.The result showed that the contents of BDNF in blood and CSF of HCH patients in recovery stage were significantly higher than those in acute stage and those of control group ( P < 0.05 ) ; the contents of BDNF in blood and CSF were negatively correlated with neurological impairment degree ( P <0.05).The results suggest that BDNF in the blood or the CSF may promote the recovery of neurological function in patients with hypertensive cerebral hemorrhage.%采用ELISA法检测30例高血压脑出血患者(观察组,因检测时间点不同而分为M1、M2亚组),30名正常人(对照组)血液和脑脊液中脑源性神经营养因子(BDNF)的含量;用美国国立卫生院神经功能评分量表(NIHSS)、汉密顿抑郁量表(HAMD)、日常生活能力Barthel指数对观察组患者按不同的时间点(发病后≤7 d,发病后≥21 d)进行评分.结果显示高血压脑出血患者恢复期血液和脑脊液BDNF显著高于急性期患者和对照组(P<0.05);血液和脑脊液BDNF含量与出院时神经功能缺损程度呈显著负相关(P<0.05).脑脊液或血液中的BDNF对高血压脑出血患者神经功能的恢复具有促进作用.

  19. Red blood cell alloimmunization after blood transfusion

    NARCIS (Netherlands)

    Schonewille, Henk

    2008-01-01

    Current pretransfusion policy requires the patients’ serum to be tested for the presence of irregular red blood cell antibodies. In case of an antibody, red blood cells lacking the corresponding antigen are transfused after an antiglobulin crossmatch. The aim of the studies in this thesis is primari

  20. Genetics Blood Card Use

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — SOP guiding collection of blood for genetics analysis. Provides stepwise instructions and guidance on how to collect DNA sample using a whole blood blot card

  1. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... known as venous thromboembolism, are highly preventable (see prevention tips below). The U.S. Surgeon General has issued ... blood conditions and increase research on the causes, prevention, and treatment. Blood clots are also potentially dangerous ...

  2. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... pregnancy: Be aware of risk factors. Know your family history. Make sure your doctor knows about any ... blood clots or blood clotting disorders in your family. Remain active, with your doctor's approval. Be aware ...

  3. Chloride test - blood

    Science.gov (United States)

    ... disease Antidiuretic hormone blood test Gastric suction Heart failure - overview Hyperventilation Ions Metabolic acidosis Multiple endocrine neoplasia (MEN) II Proximal renal tubular acidosis Respiratory acidosis Sodium blood test Review Date 5/3/2015 Updated by: Laura J. ...

  4. High blood pressure medications

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007484.htm High blood pressure medicines To use the sharing features on this page, please enable JavaScript. Treating high blood pressure will help prevent problems such as heart disease, ...

  5. Blood Pressure Medicines

    Science.gov (United States)

    High blood pressure, also called hypertension, usually has no symptoms. But it can cause serious problems such as stroke, ... kidney failure. If you cannot control your high blood pressure through lifestyle changes such as losing weight ...

  6. White Blood Cell Disorders

    Science.gov (United States)

    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  7. Low blood sugar - newborns

    Science.gov (United States)

    ... medlineplus.gov/ency/article/007306.htm Low blood sugar - newborns To use the sharing features on this page, please enable JavaScript. A low blood sugar level in newborn babies is also called neonatal ...

  8. Blood Transfusions (For Teens)

    Science.gov (United States)

    ... many precautions to confirm a patient's and donor's blood are compatible before giving a transfusion. In almost every situation, the benefits of having a blood transfusion far outweigh the risks. The Red Cross ...

  9. High blood cholesterol levels

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000403.htm High blood cholesterol levels To use the sharing features ... stroke, and other problems. The medical term for high blood cholesterol is lipid disorder, hyperlipidemia, or hypercholesterolemia. ...

  10. Rh Factor Blood Test

    Science.gov (United States)

    Tests and Procedures Rh factor blood test By Mayo Clinic Staff Rhesus (Rh) factor is an inherited protein found on the surface of ... If your blood has the protein, you're Rh positive. If your blood lacks the protein, you' ...

  11. High Blood Pressure Facts

    Science.gov (United States)

    ... More black women than men have high blood pressure. 2 Race of Ethnic Group Men (%) Women (%) African Americans 43.0 45.7 Mexican Americans 27.8 28.9 Whites 33.9 31.3 All 34.1 32.7 Top of Page Why Blood Pressure Matters View this graphic snapshot of blood pressure ...

  12. Measurements of brain-derived neurotrophic factor

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Klein, Anders Bue; Vinberg, Maj;

    2007-01-01

    Although numerous studies have dealt with changes in blood brain-derived neurotrophic factor (BDNF), methodological issues about BDNF measurements have only been incompletely resolved. We validated BDNF ELISA with respect to accuracy, reproducibility and the effect of storage and repeated freezing...... reproducibility. Female gender is associated with higher whole blood BDNF concentrations whereas age, thrombocyte count and BDNF Val66Met polymorphism were un-associated....

  13. Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp 70 Derived 14-Mer Peptide (TKD) on the Expression of NK Cell Activatory and Inhibitory Receptors on Peripheral Blood T Cells, B Cells and NKT Cells.

    Science.gov (United States)

    Hromadnikova, Ilona; Li, Shuang; Kotlabova, Katerina; Dickinson, Anne M

    2016-01-01

    Previous studies from Multhoff and colleagues reported that plasma membrane Hsp70 acts as a tumour-specific recognition structure for activated NK cells, and that the incubation of NK cells with Hsp70 and/or a 14-mer peptide derived from the N-terminal sequence of Hsp70 (TKDNNLLGRFELSG, TKD, aa 450-463) plus a low dose of IL-2 triggers NK cell proliferation and migration, and their capacity to kill cancer cells expressing membrane Hsp70. Herein, we have used flow cytometry to determine the influence of in vitro stimulation of peripheral blood mononuclear cells from healthy individuals with IL-2 or IL-15, either alone or in combination with TKD peptide on the cell surface expression of CD94, NK cell activatory receptors (CD16, NK2D, NKG2C, NKp30, NKp44, NKp46, NKp80, KIR2DL4, DNAM-1 and LAMP1) and NK cell inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2 and NKR-P1A) by CD3+CD56+ (NKT), CD3+CD4+, CD3+CD8+ and CD19+ populations. NKG2D, DNAM-1, LAMP1 and NKR-P1A expression was upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD in NKT, CD8+ T cells and B cells. CD94 was upregulated in NKT and CD8+ T cells. Concurrently, an increase in a number of CD8+ T cells expressing LIR1/ILT-2 and CD4+ T cells positive for NKR-P1A was observed. The proportion of CD8+ T cells that expressed NKG2D was higher after IL-2/TKD treatment, when compared with IL-2 treatment alone. In comparison with IL-15 alone, IL-15/TKD treatment increased the proportion of NKT cells that were positive for CD94, LAMP1 and NKRP-1A. The more potent effect of IL-15/TKD on cell surface expression of NKG2D, LIR1/ILT-2 and NKRP-1A was observed in B cells compared with IL-15 alone. However, this increase was not of statistical significance. IL-2/TKD induced significant upregulation of LAMP1 in CD8+ T cells compared with IL-2 alone. Besides NK cells, other immunocompetent cells present within the fraction of peripheral blood mononuclear cells were influenced by the treatment

  14. Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp 70 Derived 14-Mer Peptide (TKD on the Expression of NK Cell Activatory and Inhibitory Receptors on Peripheral Blood T Cells, B Cells and NKT Cells.

    Directory of Open Access Journals (Sweden)

    Ilona Hromadnikova

    Full Text Available Previous studies from Multhoff and colleagues reported that plasma membrane Hsp70 acts as a tumour-specific recognition structure for activated NK cells, and that the incubation of NK cells with Hsp70 and/or a 14-mer peptide derived from the N-terminal sequence of Hsp70 (TKDNNLLGRFELSG, TKD, aa 450-463 plus a low dose of IL-2 triggers NK cell proliferation and migration, and their capacity to kill cancer cells expressing membrane Hsp70. Herein, we have used flow cytometry to determine the influence of in vitro stimulation of peripheral blood mononuclear cells from healthy individuals with IL-2 or IL-15, either alone or in combination with TKD peptide on the cell surface expression of CD94, NK cell activatory receptors (CD16, NK2D, NKG2C, NKp30, NKp44, NKp46, NKp80, KIR2DL4, DNAM-1 and LAMP1 and NK cell inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2 and NKR-P1A by CD3+CD56+ (NKT, CD3+CD4+, CD3+CD8+ and CD19+ populations. NKG2D, DNAM-1, LAMP1 and NKR-P1A expression was upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD in NKT, CD8+ T cells and B cells. CD94 was upregulated in NKT and CD8+ T cells. Concurrently, an increase in a number of CD8+ T cells expressing LIR1/ILT-2 and CD4+ T cells positive for NKR-P1A was observed. The proportion of CD8+ T cells that expressed NKG2D was higher after IL-2/TKD treatment, when compared with IL-2 treatment alone. In comparison with IL-15 alone, IL-15/TKD treatment increased the proportion of NKT cells that were positive for CD94, LAMP1 and NKRP-1A. The more potent effect of IL-15/TKD on cell surface expression of NKG2D, LIR1/ILT-2 and NKRP-1A was observed in B cells compared with IL-15 alone. However, this increase was not of statistical significance. IL-2/TKD induced significant upregulation of LAMP1 in CD8+ T cells compared with IL-2 alone. Besides NK cells, other immunocompetent cells present within the fraction of peripheral blood mononuclear cells were influenced by

  15. On $n$-derivations

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Sattari

    2016-06-01

    Full Text Available In this article, the notion of $n-$derivation is introduced for all integers $ngeq 2$. Although all derivations are $n-$derivations,  in general these notions are not equivalent. Some properties of ordinary derivations are  investigated for $n-$derivations. Also, we show that under certain mild condition  $n-$derivations are derivations.

  16. Intracerebral transplantation of mesenchymal stem cells derived from human umbilical cord blood for improving the behavioural deficits in rats with Parkinson disease%人脐血间充质干细胞脑内移植改善帕金森病大鼠行为缺陷的研究

    Institute of Scientific and Technical Information of China (English)

    许予明; 邢莹; 杨红旗; 马杰; 孙玲

    2004-01-01

    BACKGROUND: Many researches have proved that cord blood cells can differentiate into neurons, and moreover, there are also reports regarding the successful application of cord blood in the treatments of cerebral apoplexy and other diseases of nervous system. However, it is still unknown whether cord blood stem cells can be used in the treatment of neurodegenerative diseases or not.OBJECTIVE: To investigate the feasibility and the mechanism of mesenchymal stem cells(MSCs) derived from human umbilical cord blood (HUCB) in the treatment of rats with Parkinson disease(PD).DESIGN: A randomized controlled trial.SETTING and MATERIALS: Eighteen healthy Sprague-Dawley (SD) rats of cleanness grade with a body mass from 220 g to 260 g were selected. Cord blood samples were obtained from the Department of Obstetrics and Gynecology of the Third Affiliated Hospital of Zhenzhou University. Each sample had 60 mL to 120 mL of cord blood.INTERVENTION: Lateral PD rat model induced by 6-hydroxydopamine was prepared. Rats were randomly divided into three groups: ① control group (n=6) . ② PBS group (n=6): injection of 10 μL PBS into the right striatum. ③ MSCs group( n = 6): injection of 3 × 106 MSCs( 10 μL) marked with BradU into the right striatum, apomorphine induced rotational behavior was tested after 4 weeks of transplantation, and immunohistochemistry assay was carried out to trace the survival of MSCs and the tyrosine hydroxylase (TH)-immucoreactive cells in the striatum as well.MAIN OUTCOME MEASURES: ① rotation rounds in rats of each group after transplantation. ② the results of immunohistochemistry.RESULTS: MSCs survived in the striatum. The rotational behavior induced by apomorphine in rats of MSCs group[ (212 ± 60) rounds/30 minutes] was significantly improved compared with that of control group[(340±30)rounds/minutes ] ( P < 0.05 ); However, the number of TH-positive cells in the right striatum had no statistical difference between MSCs and control group (P

  17. Cancer and blood coagulation.

    Science.gov (United States)

    Boccaccio, C; Medico, E

    2006-05-01

    In human patients, blood coagulation disorders often associate with cancer, even in its early stages. Recently, in vitro and in vivo experimental models have shown that oncogene expression, or inactivation of tumour suppressor genes, upregulate genes that control blood coagulation. These studies suggest that activation of blood clotting, leading to peritumoral fibrin deposition, is instrumental in cancer development. Fibrin can indeed build up a provisional matrix, supporting the invasive growth of neoplastic tissues and blood vessels. Interference with blood coagulation can thus be considered as part of a multifaceted therapeutic approach to cancer.

  18. Blood groups systems

    Directory of Open Access Journals (Sweden)

    Ranadhir Mitra

    2014-01-01

    Full Text Available International Society of Blood Transfusion has recently recognized 33 blood group systems. Apart from ABO and Rhesus system, many other types of antigens have been noticed on the red cell membranes. Blood grouping and cross-matching is one of the few important tests that the anaesthesiologist orders during perioperative period. Hence, a proper understanding of the blood group system, their clinical significance, typing and cross-matching tests, and current perspective are of paramount importance to prevent transfusion-related complications. Nonetheless, the knowledge on blood group system is necessary to approach blood group-linked diseases which are still at the stage of research. This review addresses all these aspects of the blood groups system.

  19. Monitoring Blood Sugar: The Importance of Checking Blood Sugar Levels

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Monitoring Blood Sugar KidsHealth > For Parents > Monitoring Blood Sugar Print A ... Tests Record Keeping The Importance of Checking Blood Sugar Levels Besides helping to keep blood sugar levels ( ...

  20. Monitoring Blood Sugar: The Importance of Checking Blood Sugar Levels

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old Monitoring Blood Sugar KidsHealth > For Parents > Monitoring Blood Sugar A ... Other Tests Record Keeping The Importance of Checking Blood Sugar Levels Besides helping to keep blood sugar ...

  1. Scientific Opinion on the substantiation of a health claim related to the combination of artichoke leaf dry extract standardised in caffeoylquinic acids, monacolin K in red yeast rice, sugar-cane derived policosanols, OPC from French maritime pine bark, garlic dry extract standardised in allicin, d-α-tocopheryl hydrogen succinate, riboflavin and inositol hexanicotinate in Limicol® and reduction of blood LDL-cholesterol concentrations pursuant to Article 14 of Regulation (EC No 1924/2006

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA

    2013-07-01

    Full Text Available Following an application from Laboratoire Lescuyer, submitted pursuant to Article 14 of Regulation (EC No 1924/2006 via the Competent Authority of France, the Panel on Dietetic Products, Nutrition and Allergies (NDA was asked to deliver an opinion on the scientific substantiation of a health claim related to the combination of artichoke leaf dry extract standardised in caffeoylquinic acids, monacolin K in red yeast rice, sugar-cane derived policosanols, OPC from French maritime pine bark, garlic dry extract standardised in allicin, d-α-tocopheryl hydrogen succinate, riboflavin and inositol hexanicotinate in Limicol® and reduction of blood LDL-cholesterol concentrations. The Panel considers that the food which is the subject of the claim is sufficiently characterised. The Panel considers that reduction of blood LDL-cholesterol concentrations is a beneficial physiological effect. High LDL-cholesterol is a risk factor in the development of coronary heart disease. In weighing the evidence, the Panel took into account that, although no evidence was provided for an LDL-cholesterol lowering effect of any of the single food constituents in Limicol® at the proposed conditions of use or as to how the ingredients individually or in any combination could contribute to the claimed effect and despite the lack of a dose-response relationship observed in one human intervention study, three human intervention studies conducted by two independent research groups showed an effect of the combination of food ingredients in Limicol® on blood LDL-cholesterol concentrations. The Panel concludes that a cause and effect relationship has been established between the consumption of the combination of artichoke leaf dry extract standardised in caffeoylquinic acids, monacolin K in red yeast rice, sugar-cane derived policosanols, OPC from French maritime pine bark, garlic dry extract standardised in allicin, d-α-tocopheryl hydrogen succinate, riboflavin and inositol

  2. Non-Invasive Optical Blood Glucose Measurement

    Directory of Open Access Journals (Sweden)

    Megha C.Pande

    2013-07-01

    Full Text Available The method for noninvasively blood glucose monitoring system is discussed in this paper. Lot of research work has been done in developing the device which is completely noninvasive to avoid the pros & cons because of frequent pricking. In this paper we are trying to analyze the noninvasive blood glucose measurement study in the near infrared region which is the most suitable region for blood glucose measurement. For this purpose we use a technique which is similar to pulseoximetry based on near infrared spectrometry .An infrared light of particular wavelength is passed through fingertip containing an arterial pulse component are derived,thus minimizing influences of basal components such as resting blood volume,skin, muscle and bone.

  3. Synthesis, micellisation and interaction of novel quaternary ammonium compounds derived from l-Phenylalanine with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine as model membrane in relation to their antibacterial activity, and their selectivity over human red blood cells.

    Science.gov (United States)

    Joondan, Nausheen; Caumul, Prakashanand; Akerman, Matthew; Jhaumeer-Laulloo, Sabina

    2015-02-01

    A series of quaternary ammonium compounds (QUATS) derived from l-Phenylalanine have been synthesized and their antibacterial efficiencies were determined against various strains of Gram-positive and Gram-negative bacteria. The antibacterial activity increased with increasing chain length, exhibiting a cut-off effect at C14 for Gram-positive and C12 for Gram-negative bacteria. The l-Phenylalanine QUATS displayed enhanced antibacterial properties with a higher cut-off point compared to their corresponding l-Phenylalanine ester hydrochlorides. The CMC was correlated with the MIC, inferring that micellar activity contributes to the cut-off effect in antibacterial activity. The hemolytic activities (HC50) of the QUATS against human red blood cells were also determined to illustrate the selectivity of these QUATS for bacterial over mammalian cells. In general, the MIC was lower than the HC50, and assessment of the micellar contribution to the antibacterial and hemolytic evaluation in TBS as a common medium confirmed that these QUATS can act as antibacterial, yet non-toxic molecules at their monomer concentrations. The interaction of the QUATS with the phospholipid vesicles (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) in the presence of 1-anilino-8-naphthalene sulfonate (ANS) and 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probes showed that the presence of the quaternary ammonium moiety causes an increase in hydrophobic interactions, thus causing an increase in antibacterial activity.

  4. Chronic blood pressure control.

    Science.gov (United States)

    Brands, Michael W

    2012-10-01

    Chronic blood pressure is maintained within very narrow limits around an average value. However, the multitude of physiologic processes that participate in blood pressure control present a bewildering array of possibilities to explain how such tight control of arterial pressure is achieved. Guyton and Coleman and colleagues addressed this challenge by creating a mathematical model that integrated the short- and long-term control systems for overall regulation of the circulation. The hub is the renal-body fluid feedback control system, which links cardiac function and vascular resistance and capacitance with fluid volume homeostasis as the foundation for chronic blood pressure control. The cornerstone of that system is renal sodium excretory capability, which is defined by the direct effect of blood pressure on urinary sodium excretion, that is, "pressure natriuresis." Steady-state blood pressure is the pressure at which pressure natriuresis balances sodium intake over time; therefore, renal sodium excretory capability is the set point for chronic blood pressure. However, this often is misinterpreted as dismissing, or minimizing, the importance of nonrenal mechanisms in chronic blood pressure control. This article explains the renal basis for the blood pressure set point by focusing on the absolute dependence of our survival on the maintenance of sodium balance. Two principal threats to sodium balance are discussed: (1) a change in sodium intake or renal excretory capability and (2) a change in blood pressure. In both instances, circulatory homeostasis is maintained because the sodium balance blood pressure set point is reached.

  5. Right patient, Right blood

    DEFF Research Database (Denmark)

    Selberg, Hanne; Madsen, Trine Stougaard

    2014-01-01

    Right patient, Right Blood Simulation based training in blood transfusion practice in nursing education Background: In spite of strict checking procedures to handling transfusion of blood severe adverse reactions are likely to happen and the major cause of morbidity occurs to be liable to human...... errors. Nursing students have limited possibility to practice safe blood transfusion during clinical placements. We introduced simulation-based workshops to reinforce safe transfusion practice and thus increase patient safety but equally important to bridge the gap between theory and practice. Objectives......: The objective of the current study was to test workshops focusing on procedures of safe blood transfusion by combining theory and practice, integrating current guidelines on safe blood transfusion and hereby help students to better recognize and handle errors and adverse reactions. Methods: 372 third year...

  6. Photosensitized inactivation of infectious blood-borne human parasites

    Science.gov (United States)

    Judy, Millard M.; Sogandares-Bernal, Franklin M.; Matthews, James Lester

    1995-05-01

    Blood-borne viruses and protozoan parasites that are infectious to humans pose risk world-wide of infection transmission through blood and blood product transfusion. Blood-borne infectious viruses include human immunodeficiency virus (HIV-I), which causes AIDS; hepatitis C virus, which can cause chronic hepatitis; and cytomegalovirus, which can be dangerous to immunocompromised patients, e.g., the newborn, transplant recipients, and AIDS patients. Infectious blood-borne protozoan parasites include Trypanosoma cruzi, which causes Chagas' disease, endemic throughout Central and South America; the Trypanosoma species causing African sleeping sickness endemic in Central Africa; and Plasmodium falciparum, which causes malignant and increasingly drug- resistant human malaria prevalent throughout the tropics. Some researchers have focused on using photosensitizers to inactivate HIV-I and other viruses in whole blood, packed red cells, and platelet concentrates without compromising blood product function. Our group previously has reported photosensitized in vitro inactivation of P. falciparum and the mouse malaria organism Plasmodium berghei in whole blood using hematoporphyrin derivative (HPD) and of T. cruzi using benzoporphyrin derivatives BPDMA and BPDDA, dihematoporphyrin ether (DHE), and hydroxyethylvinyldeuteroporphyrin (HEVD). These results suggest that continued investigation is warranted to evaluate the potential for photosensitized inactivation of blood-borne parasites in blood banking.

  7. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... just had a baby, you are at greater risk of developing a blood clot. Blood clots in pregnant women tend to form in the deep veins of the legs or in the pelvic area. This condition is known as deep vein thrombosis (DVT). Pulmonary embolism (PE) is a life-threatening ...

  8. Virtual blood bank.

    Science.gov (United States)

    Wong, Kit Fai

    2011-01-24

    Virtual blood bank is the computer-controlled, electronically linked information management system that allows online ordering and real-time, remote delivery of blood for transfusion. It connects the site of testing to the point of care at a remote site in a real-time fashion with networked computers thus maintaining the integrity of immunohematology test results. It has taken the advantages of information and communication technologies to ensure the accuracy of patient, specimen and blood component identification and to enhance personnel traceability and system security. The built-in logics and process constraints in the design of the virtual blood bank can guide the selection of appropriate blood and minimize transfusion risk. The quality of blood inventory is ascertained and monitored, and an audit trail for critical procedures in the transfusion process is provided by the paperless system. Thus, the virtual blood bank can help ensure that the right patient receives the right amount of the right blood component at the right time.

  9. Blood Test: Bilirubin

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Blood Test: Bilirubin KidsHealth > For Parents > Blood Test: Bilirubin A A A What's in this article? What ... Análisis de sangre: bilirrubina What It Is A bilirubin test measures the level of bilirubin (a byproduct ...

  10. Virtual blood bank

    Directory of Open Access Journals (Sweden)

    Kit Fai Wong

    2011-01-01

    Full Text Available Virtual blood bank is the computer-controlled, electronically linked information management system that allows online ordering and real-time, remote delivery of blood for transfusion. It connects the site of testing to the point of care at a remote site in a real-time fashion with networked computers thus maintaining the integrity of immunohematology test results. It has taken the advantages of information and communication technologies to ensure the accuracy of patient, specimen and blood component identification and to enhance personnel traceability and system security. The built-in logics and process constraints in the design of the virtual blood bank can guide the selection of appropriate blood and minimize transfusion risk. The quality of blood inventory is ascertained and monitored, and an audit trail for critical procedures in the transfusion process is provided by the paperless system. Thus, the virtual blood bank can help ensure that the right patient receives the right amount of the right blood component at the right time.

  11. Give blood at CERN

    CERN Multimedia

    SC Unit

    2008-01-01

    ACCIDENTS and ILLNESSES don’t take a break! DO SOMETHING AMAZING - GIVE BLOOD! IT’S IN ALL OUR INTERESTS. 30 July 2008 from 9.30 a.m. to 4 p.m. CERN RESTAURANT NOVAE First floor - Salle des Pas Perdus After you have given blood, you are invited to partake of refreshments kindly offered by NOVAE.

  12. How Blood Clots

    Science.gov (United States)

    ... Japanese Espaniol Find information on medical topics, symptoms, drugs, procedures, news and more, written in everyday language. * This is ... Process How Blood Clots Resources In This Article Drugs Mentioned In This Article ... of the Blood (News) Is Binge-Watching Hazardous to Your Health? (News) ...

  13. [Blood Count Specimen].

    Science.gov (United States)

    Tamura, Takako

    2015-12-01

    The circulating blood volume accounts for 8% of the body weight, of which 45% comprises cellular components (blood cells) and 55% liquid components. We can measure the number and morphological features of blood cells (leukocytes, red blood cells, platelets), or count the amount of hemoglobin in a complete blood count: (CBC). Blood counts are often used to detect inflammatory diseases such as infection, anemia, a bleeding tendency, and abnormal cell screening of blood disease. This count is widely used as a basic data item of health examination. In recent years, clinical tests before consultation have become common among outpatient clinics, and the influence of laboratory values on consultation has grown. CBC, which is intended to count the number of raw cells and to check morphological features, is easily influenced by the environment, techniques, etc., during specimen collection procedures and transportation. Therefore, special attention is necessary to read laboratory data. Providing correct test values that accurately reflect a patient's condition from the laboratory to clinical side is crucial. Inappropriate medical treatment caused by erroneous values resulting from altered specimens should be avoided. In order to provide correct test values, the daily management of devices is a matter of course, and comprehending data variables and positively providing information to the clinical side are important. In this chapter, concerning sampling collection, blood collection tubes, dealing with specimens, transportation, and storage, I will discuss their effects on CBC, along with management or handling methods.

  14. Blood Gases Test

    Science.gov (United States)

    ... prevent any bleeding from the site. Sometimes mixed venous blood taken from a central line is used in particular situations, such as in cardiac catheterization labs and by transplant services. Careful interpretation of the results is required. Peripheral venous blood, such as that taken from a vein ...

  15. BLOOD DONORS CAMPAIGN

    CERN Multimedia

    2001-01-01

    A blood donors campaign, organized by the Centre de Transfusion Sanguine of Geneva will be held at CERN on Tuesday 13 March 2001 in restaurant nr 2, from 9.00 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.

  16. BLOOD DONORS CAMPAIGN

    CERN Multimedia

    2001-01-01

    A blood donors campaign, organized by the Centre de Transfusion d'Annemasse will be held at CERN on Tuesday 14 November 2001 in restaurant nr 2, from 9.00 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.

  17. BLOOD DONORS CAMPAIGN

    CERN Multimedia

    Medical Service

    2002-01-01

    Tuesday 19 March 2002 in restaurant nr 2, from 9.00 to 16.30 hrs A blood donors campaign, organized by the Centre de Transfusion sanguine of Geneva If you already have a card giving your blood group, please bring this with you.

  18. BLOOD DONORS CAMPAIGN

    CERN Document Server

    2000-01-01

    A blood donors campaign, organized by the Établissement de Transfusion de Rhône-Alpes will be held at CERN on Tuesday 14 November 2000 in restaurant nr 2, from 8.30 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.

  19. BLOOD DONORS CAMPAIGN

    CERN Document Server

    2002-01-01

    Wednesday 13 November 2002 in restaurant nr 2, from 8.30 to 16.30 hrs will be held a blood donors campaign, organized by the Etablissement de Transfusion de Haute-Savoie If you already have a card giving your blood group, please bring this with you.

  20. Blood Type Game

    Science.gov (United States)

    ... Time Donors The Fear of Needles LGBTQ+ Donors Blood Donor Community Real Stories SleevesUp Games Facebook Avatars and Badges Banners eCards Enter your zip code to find: Regional Promotions Local News Blood Drives & More! Or find the Red Cross chapter ...

  1. Preventing High Blood Pressure

    Science.gov (United States)

    ... Web Sites Division for Heart Disease and Stroke Prevention Stroke Heart Disease Cholesterol Salt Million Hearts® WISEWOMAN Preventing High Blood Pressure: Healthy Living Habits Recommend on Facebook Tweet Share Compartir By living a healthy lifestyle, you can help keep your blood pressure in ...

  2. Blood pressure load does not add to ambulatory blood pressure level for cardiovascular risk stratification

    DEFF Research Database (Denmark)

    Li, Yan; Thijs, Lutgarde; Boggia, José

    2014-01-01

    Experts proposed blood pressure (BP) load derived from 24-hour ambulatory BP recordings as a more accurate predictor of outcome than level, in particular in normotensive people. We analyzed 8711 subjects (mean age, 54.8 years; 47.0% women) randomly recruited from 10 populations. We expressed BP...

  3. 经血源子宫内膜干细胞复合3D打印PLGA支架体外培养的相容性研究%Cellular Compatibility of Menstrual Blood-derived Mesenchymal Stem Cells in Three-dimensional Printing PLGA Scaffolds

    Institute of Scientific and Technical Information of China (English)

    许世兵; 单乐天; 金红婷; 王萍儿; 童培建; 肖鲁伟

    2015-01-01

    Objective] To investigate the feasibility of using three-dimensional(3D) printing PLGA loaded with menstrual blood-derived mesenchymal stem cells(MenSCs) as scaffolds for bone cartilage tissue engineering. [Methods] Three-dimensional printing PLGA was preprocessed. The five generation MenSCs were utilized. use invert microscope to observe cells biological property. According to 1.0 ×106/mL cells seeded onto PLGA scaffold composite culture, invert microscope, Mico-CT, scanning electron microscope and histopathology were observed.[Results] MSCs grew well, cells were plated to grow, fusiform or spindle row, thin cytoplasmic and nuclear circle centered, with fibroblast morphology. Cells to the fifth generation had long spindle cell monolayer and swirling arrangement. PLGA scaffolds exhibited microscopic interconnected porous structure, loose structure, large pores and mutual traffic, thinner hole wall. MenSCs on PLGA scaffold grew well, mainly in the scaffolds surface and inside growth, the scaffolds aperture had cell matrix organization connection.[Conclusion] MenSCs are ideal seeding cells for bone cartilage tissue engineering. And the PLGA scaffolds by three-dimensional printing with MenSCs may be in vitro construction as bone cartilage formation.%[目的]通过经血源子宫内膜干细胞(menstrual blood-derived mesenchymal stem cells, MenSCs)与3D打印PLGA支架材料的复合培养,探讨构建组织工程化骨软骨的可行性。[方法]预处理3D打印PLGA支架,取第5代MenSCs,倒置显微镜下观察细胞生物学特性,按1.0×106/mL的密度接种到PLGA支架材料上复合培养,通过倒置显微镜、Mico-CT、扫描电镜和组织病理学进行观察,并借此判断MenSCs与3D打印PLGA支架材料复合体外培养的融合性。[结果] MenSCs生长良好,细胞平铺生长,呈梭形或纺锤形,胞质薄,核圆居中,具有成纤维细胞形态。细胞传至第5代,为长梭形细胞单层,呈漩涡状排列

  4. Cocoa, blood pressure, and cardiovascular health.

    Science.gov (United States)

    Ferri, Claudio; Desideri, Giovambattista; Ferri, Livia; Proietti, Ilenia; Di Agostino, Stefania; Martella, Letizia; Mai, Francesca; Di Giosia, Paolo; Grassi, Davide

    2015-11-18

    High blood pressure is an important risk factor for cardiovascular disease and cardiovascular events worldwide. Clinical and epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. According to this, cocoa has a high content in polyphenols, especially flavanols. Flavanols have been described to exert favorable effects on endothelium-derived vasodilation via the stimulation of nitric oxide-synthase, the increased availability of l-arginine, and the decreased degradation of NO. Cocoa may also have a beneficial effect by protecting against oxidative stress alterations and via decreased platelet aggregation, decreased lipid oxidation, and insulin resistance. These effects are associated with a decrease of blood pressure and a favorable trend toward a reduction in cardiovascular events and strokes. Previous meta-analyses have shown that cocoa-rich foods may reduce blood pressure. Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events. A 3 mmHg systolic blood pressure reduction has been estimated to decrease the risk of cardiovascular and all-cause mortality. This paper summarizes new findings concerning cocoa effects on blood pressure and cardiovascular health, focusing on putative mechanisms of action and "nutraceutical " viewpoints.

  5. Erythropoietic Potential of CD34+ Hematopoietic Stem Cells from Human Cord Blood and G-CSF-Mobilized Peripheral Blood

    Directory of Open Access Journals (Sweden)

    Honglian Jin

    2014-01-01

    Full Text Available Red blood cell (RBC supply for transfusion has been severely constrained by the limited availability of donor blood and the emergence of infection and contamination issues. Alternatively, hematopoietic stem cells (HSCs from human organs have been increasingly considered as safe and effective blood source. Several methods have been studied to obtain mature RBCs from CD34+ hematopoietic stem cells via in vitro culture. Among them, human cord blood (CB and granulocyte colony-stimulating factor-mobilized adult peripheral blood (mPB are common adult stem cells used for allogeneic transplantation. Our present study focuses on comparing CB- and mPB-derived stem cells in differentiation from CD34+ cells into mature RBCs. By using CD34+ cells from cord blood and G-CSF mobilized peripheral blood, we showed in vitro RBC generation of artificial red blood cells. Our results demonstrate that CB- and mPB-derived CD34+ hematopoietic stem cells have similar characteristics when cultured under the same conditions, but differ considerably with respect to expression levels of various genes and hemoglobin development. This study is the first to compare the characteristics of CB- and mPB-derived erythrocytes. The results support the idea that CB and mPB, despite some similarities, possess different erythropoietic potentials in in vitro culture systems.

  6. [Contributions of the Council of Europe's Blood Transfusion Steering Committee to the determination of rules for the selection of donors of blood and blood components and the study of sexual behaviors having an impact on blood safety].

    Science.gov (United States)

    Behr-Gross, M-E; Heiden, M; Norda, R

    2013-05-01

    In November 2009, the Council of Europe's Blood Transfusion Steering Committee created a group of experts to explore the problem of behaviors having an impact on the management of donors of blood and blood components and on blood transfusion safety in Europe. This ad hoc group sought a harmonised interpretation of temporary exclusion (or temporary deferral), as opposed to permanent exclusion (or permanent deferral), in the context of the selection of donors of blood and blood components. It was also given the mandate to assess, on the basis of available data, the possibility of differentiating "at risk" behaviours from behaviours "at high risk" of contamination by serious infectious diseases transmitted by blood, blood components or derived therapeutic products. The primary objective of this work was to ensure the safety of blood, blood components and derived therapeutic products for future recipients by promoting a risk analysis-based approach, given that some countries envisaged amending their provisions for donor selection. However, a risk analysis can only be performed on groups, not individuals, which may give the impression of a discriminatory approach, so it needed to be justified in the context of transfusion safety. A collaborative project, which included an investigation phase, led to the drafting of a technical memorandum that summarised the data collected in ten Council of Europe member states on the selection criteria for blood donors and the epidemiology of infectious diseases (with a focus on human immunodeficiency virus) in the general population and among blood donors. The technical memorandum was published in 2011 on the European Directorate for the Quality of Medicines and Healthcare website dedicated to this project. A draft resolution of the Committee of Ministers of the Council of Europe was then developed by the Council of Europe's Blood Transfusion Steering Committee. This text was circulated among member and observer states of the Council

  7. Derived logarithmic geometry I

    OpenAIRE

    Steffen, Sagave; Timo, Schurg; Gabriele, Vezzosi

    2016-01-01

    In order to develop the foundations of logarithmic derived geometry, we introduce a model category of logarithmic simplicial rings and a notion of derived log \\'etale maps and use this to define derived log stacks.

  8. High Blood Pressure Fact Sheet

    Science.gov (United States)

    ... High Blood Pressure Salt Cholesterol Million Hearts® WISEWOMAN High Blood Pressure Fact Sheet Language: English Español (Spanish) Recommend on ... time. High blood pressure is also called hypertension. High Blood Pressure in the United States Having high blood pressure ...

  9. Home monitoring of blood pressure

    OpenAIRE

    McGrath, Barry P.

    2015-01-01

    Home blood pressure monitoring is the self-measurement of blood pressure by patients. In the diagnosis and management of high blood pressure it is complementary to 24-hour ambulatory blood pressure monitoring and clinic blood pressure measurements. Home monitoring can also help to identify white-coat and masked hypertension.

  10. Survival after blood transfusion

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Ahlgren, Martin; Rostgaard, Klaus

    2008-01-01

    of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first...... the SMR remained significantly 1.3-fold increased. CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion-transmitted disease...... as well as for cost-benefit estimation of new blood safety interventions....

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy ...

  12. Cord-Blood Banking

    Science.gov (United States)

    ... blood banks may capitalize on the fears of vulnerable new parents by providing misleading information about the statistics of stem cell transplants. Parents of children of ethnic or racial minorities, adopted children, or ...

  13. High Blood Pressure

    Science.gov (United States)

    ... may have tax advantages for you. Workplace giving Workplace giving Find a list of the most common ... pressure and cholesterol. Exercise can also help relieve stress, another common cause of high blood pressure. To ...

  14. ALP - blood test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003470.htm ALP - blood test To use the sharing features on this page, please enable JavaScript. Alkaline phosphatase (ALP) is a protein found in all body tissues. ...

  15. Order of blood draw

    DEFF Research Database (Denmark)

    Cornes, Michael; van Dongen-Lases, Edmée; Grankvist, Kjell

    2017-01-01

    , CLSI) guidelines recommend that the order of draw of blood during phlebotomy should be blood culture/sterile tubes, then plain tubes/gel tubes, then tubes containing additives. This prevents contamination of sample tubes with additives from previous tubes that could cause erroneous results. There have...... Medicine Working Group for the Preanalytical Phase (EFLM WG-PRE) provides an overview and summary of the literature with regards to order of draw in venous blood collection. Given the evidence presented in this article, the EFLM WG-PRE herein concludes that a significant frequency of sample contamination...... does occur if order of draw is not followed during blood collection and when performing venipuncture under less than ideal circumstances, thus putting patient safety at risk. Moreover, given that order of draw is not difficult to follow and knowing that ideal phlebotomy conditions and protocols...

  16. Types of Blood Donations

    Science.gov (United States)

    ... blood' every 56 days. Back to Top Platelet Apheresis Platelet donations are collected at select American Red ... about Platelet Apheresis Donations » Back to Top Plasma Apheresis Plasma is collected simultaneously with a platelet donation ...

  17. Blood Donation Process

    Science.gov (United States)

    ... types, such as platelets, red cells or plasma ( apheresis donations ) can take up to 2 hours. When ... Disease Testing Reimbursement Resources Educational Resources PACS Therapeutic Apheresis Our Supporters Blood App HS Leadership Program SleevesUp ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ... us get closer to curing diabetes and better treatments for those living with diabetes. Other Ways to ...

  19. Hyperglycemia (High Blood Glucose)

    Science.gov (United States)

    ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ... us get closer to curing diabetes and better treatments for those living with diabetes. Other Ways to ...

  20. High Blood Pressure (Hypertension)

    Science.gov (United States)

    ... already been diagnosed with high blood pressure. Try yoga and meditation. Yoga and meditation not only can strengthen your body ... Accessed Sept. 21, 2015. Hu B, et al. Effects of psychological stress on hypertension in middle-aged ...

  1. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... blood conditions. back to top Antiphospholipid Antibody Syndrome: A Patient's Journey back to top Where Can I ... and help move hematology forward. Learn more Find a Hematologist Search a database of practicing hematologists in ...

  2. Vitamin A blood test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003570.htm Vitamin A blood test To use the sharing features on this page, please enable JavaScript. The vitamin A test measures the level of vitamin A ...

  3. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... to Give Close Are You at Risk? Home Prevention Diagnosing Diabetes and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity ...

  4. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... First Edition Abstracts Blood Advances A peer-reviewed journal with a unique focus on scholarly and educational ... Advances A peer-reviewed, online only, open access journal with a unique focus on scholarly and educational ...

  5. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C ... your doctor may change the amount of your medication or insulin or possibly the timing of when ...

  6. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... How Grant Money is Divided Funding the Next Generation of Brilliant Researchers Our Research Foundation Diabetes Pro: ... they build up in your blood, which can lead to ketoacidosis. Ketoacidosis is life-threatening and needs ...

  7. What Causes High Blood Pressure?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Causes of High Blood Pressure Changes, either from genes or the environment, in ... and blood vessel structure and function. Biology and High Blood Pressure Researchers continue to study how various changes in ...

  8. Prevention of High Blood Pressure

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Prevention of High Blood Pressure Healthy lifestyle habits, proper use of medicines, and ... prevent high blood pressure or its complications. Preventing High Blood Pressure Onset Healthy lifestyle habits can help prevent high ...

  9. High Red Blood Cell Count

    Science.gov (United States)

    Symptoms High red blood cell count By Mayo Clinic Staff A high red blood cell count is an increase in oxygen-carrying cells in your bloodstream. Red blood cells transport oxygen from your lungs to tissues throughout ...

  10. Manage your blood sugar (image)

    Science.gov (United States)

    Checking your blood sugar levels often and writing down the results will tell you how well you are managing your diabetes so you ... possible. The best times to check your blood sugar are before meals and at bedtime. Your blood ...

  11. Blood in the Urine (Hematuria)

    Science.gov (United States)

    ... of Healthy Breakfasts Shyness Blood in the Urine (Hematuria) KidsHealth > For Teens > Blood in the Urine (Hematuria) ... español Sangre en la orina (hematuria) What Is Hematuria? When blood gets into a person's urine (pee), ...

  12. Luteinizing hormone (LH) blood test

    Science.gov (United States)

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  13. Pulsatile blood flow, shear force, energy dissipation and Murray's Law

    Directory of Open Access Journals (Sweden)

    Bengtsson Hans-Uno

    2006-08-01

    Full Text Available Abstract Background Murray's Law states that, when a parent blood vessel branches into daughter vessels, the cube of the radius of the parent vessel is equal to the sum of the cubes of the radii of daughter blood vessels. Murray derived this law by defining a cost function that is the sum of the energy cost of the blood in a vessel and the energy cost of pumping blood through the vessel. The cost is minimized when vessel radii are consistent with Murray's Law. This law has also been derived from the hypothesis that the shear force of moving blood on the inner walls of vessels is constant throughout the vascular system. However, this derivation, like Murray's earlier derivation, is based on the assumption of constant blood flow. Methods To determine the implications of the constant shear force hypothesis and to extend Murray's energy cost minimization to the pulsatile arterial system, a model of pulsatile flow in an elastic tube is analyzed. A new and exact solution for flow velocity, blood flow rate and shear force is derived. Results For medium and small arteries with pulsatile flow, Murray's energy minimization leads to Murray's Law. Furthermore, the hypothesis that the maximum shear force during the cycle of pulsatile flow is constant throughout the arterial system implies that Murray's Law is approximately true. The approximation is good for all but the largest vessels (aorta and its major branches of the arterial system. Conclusion A cellular mechanism that senses shear force at the inner wall of a blood vessel and triggers remodeling that increases the circumference of the wall when a shear force threshold is exceeded would result in the observed scaling of vessel radii described by Murray's Law.

  14. Assessment of blood-retinal barrier integrity.

    Science.gov (United States)

    Vinores, S A

    1995-01-01

    The blood-retinal barrier consists of two components which are comprised of the retinal vascular endothelium and the retinal pigment epithelium, respectively. Its functional integrity can be recognized by tight junctions between these cells with a paucity of endocytic vesicles within them and the presence of the molecules that regulate the ionic and metabolic gradients that constitute the barrier. The barrier is compromised in several disease processes and by a variety of agents, but in most cases the location and mechanism for barrier failure is not understood. Perfusion with a variety of radiolabeled tracer molecules, vitreous fluorophotometry, or magnetic resonance imaging can be used to quantitate blood-retinal barrier leakage. Fluorescein angiography or magnetic resonance imaging can localize sites of leakage in vivo with limited resolution. Evans blue dye can be used to visualize blood-retinal barrier failure in gross pathological specimens and immuno-histochemical labeling of serum proteins such as albumin or fibrinogen can be used to localize sites of blood-retinal barrier breakdown by light microscopy. Tracers such as horseradish peroxidase, microperoxidase, or lanthanum, or the immunocytochemical demonstration of albumin can be used to reveal blood-retinal barrier breakdown at the ultrastructural level and provide insights into the mechanisms involved. This review discusses the advantages and limitations of each of these methods to aid in selection of the appropriate techniques to derive the desired information.

  15. Transfusion and blood donation in comic strips.

    Science.gov (United States)

    Lefrère, Jean-Jacques; Danic, Bruno

    2013-07-01

    The representation of blood transfusion and donation of blood in the comic strip has never been studied. The comic strip, which is a relatively recent art, emerged in the 19th century before becoming a mass medium during the 20th century. We have sought, by calling on collectors and using the resources of Internet, comic strips devoted, wholly or in part, to the themes of transfusion and blood donation. We present some of them here in chronologic order, indicating the title, country of origin, year of publication, and names of authors. The theme of the superhero using transfusion to transmit his virtues or his powers is repeated throughout the 20th century in North American comic strips. More recently, comic strips have been conceived from the outset with a promotional aim. They perpetuate positive images and are directed toward a young readership, wielding humor to reduce the fear of venipuncture. Few comic strips denounce the abuse of the commercialization of products derived from the human body. The image of transfusion and blood donation given by the comic strips is not to be underestimated because their readership is primarily children, some of whom will become blood donors. Furthermore, if some readers are transfused during their lives, the impact of a memory more or less conscious of these childhood readings may resurface, both in hopes and in fears.

  16. Detection of testosterone esters in blood.

    Science.gov (United States)

    Forsdahl, Guro; Erceg, Damir; Geisendorfer, Thomas; Turkalj, Mirjana; Plavec, Davor; Thevis, Mario; Tretzel, Laura; Gmeiner, Günter

    2015-01-01

    Injections of synthetic esters of testosterone are among the most common forms of testosterone application. In doping control, the detection of an intact ester of testosterone in blood gives unequivocal proof of the administration of exogenous testosterone. The aim of the current project was to investigate the detection window for injected testosterone esters as a mixed substance preparation and as a single substance preparation in serum and plasma. Furthermore, the suitability of different types of blood collection devices was evaluated. Collection tubes with stabilizing additives, as well as non-stabilized serum separation tubes, were tested. A clinical study with six participants was carried out, comprising a single intramuscular injection of either 1000 mg testosterone undecanoate (Nebido(®)) or a mixture of 30 mg testosterone propionate, 60 mg testosterone phenylpropionate, 60 mg testosterone isocaproate, and 100 mg testosterone decanoate (Sustanon(®)). Blood was collected throughout a testing period of 60 days. The applied analytical method for blood analysis included liquid-liquid extraction and preparation of oxime derivatives, prior to TLX-sample clean-up and liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection. All investigated testosterone esters could be detected in post-administration blood samples. The detection time depended on the type of ester administered. Furthermore, results from the study show that measured blood concentrations of especially short-chained testosterone esters are influenced by the type of blood collection device applied. The testosterone ester detection window, however, was comparable.

  17. Profiles of blood and blood component transfusion recipients in Zimbabwe

    NARCIS (Netherlands)

    Mafirakureva, Nyashadzaishe; Khoza, Star; Hassall, Oliver; Faragher, Brian E.; Kajja, Isaac; Mvere, David A.; Emmanuel, Jean C.; Postma, Maarten J.; van Hulst, Marinus

    2015-01-01

    Background. There are limited published data on the characteristics of blood transfusion recipients in sub-Saharan Africa. This study describes the demographic characteristics of blood transfusion recipients and patterns of blood and blood component use in Zimbabwe. Materials and methods. Data on th

  18. Characterization of Imidazoline Receptors in Blood Vessels for the Development of Antihypertensive Agents

    OpenAIRE

    Mei-Fen Chen; Jo-Ting Tsai; Li-Jen Chen; Tung-Pi Wu; Jia-Jang Yang; Li-Te Yin; Yu-lin Yang; Tai-An Chiang; Han-Lin Lu; Ming-Chang Wu

    2014-01-01

    It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R) may reduce the blood pressure in spontaneously hypertensive rats (SHRs). Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s). Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metform...

  19. Blood Vessel Tension Tester

    Science.gov (United States)

    1978-01-01

    In the photo, a medical researcher is using a specially designed laboratory apparatus for measuring blood vessel tension. It was designed by Langley Research Center as a service to researchers of Norfolk General Hospital and Eastern Virginia Medical School, Norfolk, Virginia. The investigators are studying how vascular smooth muscle-muscle in the walls of blood vessels-reacts to various stimulants, such as coffee, tea, alcohol or drugs. They sought help from Langley Research Center in devising a method of measuring the tension in blood vessel segments subjected to various stimuli. The task was complicated by the extremely small size of the specimens to be tested, blood vessel "loops" resembling small rubber bands, some only half a millimeter in diameter. Langley's Instrumentation Development Section responded with a miniaturized system whose key components are a "micropositioner" for stretching a length of blood vessel and a strain gage for measuring the smooth muscle tension developed. The micropositioner is a two-pronged holder. The loop of Mood vessel is hooked over the prongs and it is stretched by increasing the distance between the prongs in minute increments, fractions of a millimeter. At each increase, the tension developed is carefully measured. In some experiments, the holder and specimen are lowered into the test tubes shown, which contain a saline solution simulating body fluid; the effect of the compound on developed tension is then measured. The device has functioned well and the investigators say it has saved several months research time.

  20. Blood flow and microgravity

    Science.gov (United States)

    Bureau, Lionel; Coupier, Gwennou; Dubois, Frank; Duperray, Alain; Farutin, Alexander; Minetti, Christophe; Misbah, Chaouqi; Podgorski, Thomas; Tsvirkun, Daria; Vysokikh, Mikhail

    2017-01-01

    The absence of gravity during space flight can alter cardio-vascular functions partially due to reduced physical activity. This affects the overall hemodynamics, and in particular the level of shear stresses to which blood vessels are submitted. Long-term exposure to space environment is thus susceptible to induce vascular remodeling through a mechanotransduction cascade that couples vessel shape and function with the mechanical cues exerted by the circulating cells on the vessel walls. Central to such processes, the glycocalyx - i.e. the micron-thick layer of biomacromolecules that lines the lumen of blood vessels and is directly exposed to blood flow - is a major actor in the regulation of biochemical and mechanical interactions. We discuss in this article several experiments performed under microgravity, such as the determination of lift force and collective motion in blood flow, and some preliminary results obtained in artificial microfluidic circuits functionalized with endothelium that offer interesting perspectives for the study of the interactions between blood and endothelium in healthy condition as well as by mimicking the degradation of glycocalyx caused by long space missions. A direct comparison between experiments and simulations is discussed. xml:lang="fr"

  1. Blood and war.

    Science.gov (United States)

    Hedley-Whyte, John; Milamed, Debra R

    2010-09-01

    In 1894 Ulsterman and pathologist Almroth Wright described the citation of blood. Twenty-one years later it was introduced into wartime and clinical practice. Harvard Medical School had a large part in providing Colonel Andrew Fullerton, later Professor of Surgery, Queen's Belfast, with the intellectual and practical help for the Allies to deploy blood on the post-Somme Western Front and in Salonika. The key investigators and clinicians were Americans and Canadians who with Fullerton and Wright instructed the Allies. The key enablers were two Harvard-trained surgeons surnamed Robertson-Oswald H. ("Robby") and L. Bruce (no relation). Physician Roger I. Lee of Harvard, surgeon George W Crile of Cleveland, Peyton Rous of the Rockefeller Institute and Richard Lewisohn of Mount Sinai Hospital, both located in the Upper East Side of New York City, played key roles.By Armistice in 1918, indirect citrated nutrient-enhanced blood transfusion was widely used by the Allies. Geoffrey Keynes was taught the techniques of blood transfusion by Dr. Benjamin Harrison Alton of Harvard at a Casualty Clearing Station near Albert at the time of the Battle of Passchendaele. Professor "Robby" Robertson, DSO, Sir Geoffrey Keynes and Sir Thomas Houston established blood banking.

  2. Infections Transmitted By the Transfusion of Blood and Blood Products

    Directory of Open Access Journals (Sweden)

    Tekin A.

    2011-05-01

    Full Text Available Especially viral hepatitis viruses and human immunodeficiency virus(HIV which were transmitted by the transfusion of blood and blood products have been an important public health problem for a long time on the world. Transfusion of blood and blood products is an ideal and an easiest and a simplest route for transmission of infectious diseases. It is known that many infectious agents, either bacterial, viral, parasitic and fungal agents may be transmitted by the transfusion of blood and blood products. In present study, we reviewed infection diseases that transmitted by the transfusion of blood and blood products.Additionally, we were aimed to emphasize a rare but a very important complication of transfusion of blood and blood products.

  3. Laboratory blood group examination of proteolysis degradation human blood

    OpenAIRE

    Beta Ahlam Gizela, Beta Ahlam Gizela

    2015-01-01

    Background: Blood group examination has many purposes and one of them is identification. In several forensic cases there is incompatibility of blood group in corpse and in other evidences usually used blood group examination is serum agglutination method. From the previous study, it was found that there was increasing osmotic fragility of red cell. For that reason, we need to know how the result of blood group tests in degradation human blood.Objective: The purpose of this study is to know bl...

  4. Storing Blood Cells

    Science.gov (United States)

    1976-01-01

    The National Cancer Institute worked with Goddard Space Flight Center to propose a solution to the blood-cell freezing problem. White blood cells and bone marrow are stored for future use by leukemia patients as a result of Goddard and Jet Propulsion Laboratory expertise in electronics and cryogenics. White blood cell and bone marrow bank established using freezing unit. Freezing unit monitors temperature of cells themselves. Thermocouple placed against polyethylene container relays temperature signals to an electronic system which controls small heaters located outside container. Heaters allow liquid nitrogen to circulate at constant temperature and maintain consistent freezing rate. Ability to freeze, store, and thaw white cells and bone marrow without damage is important in leukemia treatment.

  5. The Myocardial Detection of Acute Myocardial Infarction rats Transplant into Human Umbilical cord Blood Derived Mesenchymal stem cell%急性心肌梗死大鼠移植入人脐带血间充质干细胞后心肌组织检测

    Institute of Scientific and Technical Information of China (English)

    何志裕; 陆东风

    2015-01-01

    目的探讨经尾静脉脐血间充质干细胞(mesenchymal stem cells,MSCs)移植到急性心肌梗死大鼠体内,观察其是否可以存活及是否向心肌组织分化。方法无菌条件下采集健康育龄产妇正常分娩胎儿脐带血,通过Mesen-cult培养基条件培养,取P2代细胞用流式细胞仪检测细胞表面CD29、CD34、CD45、CD105标志。将36只SD大鼠随机分成MSCs移植组、假手术组和心肌梗死植组各12只,结扎左冠状动脉前降支制备大鼠心肌梗死模型。1周后,经尾静脉注射带DAPI标记的脐血MSCs。4周后行免疫组织化学检测移植细胞存活与分化情况及检测梗死组织中FactorⅧ表达来比较三组微血管密度。结果流式细胞仪检测第2代的脐血MSCs 结果显示, P2代MSCs 不表达或极弱表达CD34,CD45造血细胞标志,稳定地高表达CD29,CD105间充质细胞相关的表面抗原标记。这与骨髓MSCs的表面抗原标志相一致。移植后4周,移植组心肌组织中可以观察到DAPI标记细胞存在,但标记细胞并未表达Troponin-T及con-nexin43,免疫组化染色检测示MSCs移植组心肌微血管密度(MVD)明显高于心梗组和假手术组。结论将脐血单个核细胞接种在mesencult培养基中可以在体外成功的培养出较纯化的脐血MSCs,脐血MSCs的免疫表型符合间充质干细胞特征,脐血MSCs移植能刺激梗死部位血管生成,但未向心肌细胞分化。%Objective To investigate the human umbilical cord blood mesenchymal stem cells was transplanted into the rats of acute myocardial infarction ( AMI) to observe the mesenchymal stem cells whether it can survive and whether to myocardial tissue differentiation .Methods Human umbilical cord blood sam-ples were collected from healthy mothers .ALL samples was culture medium consisted of Mesencult ( a kind of medium special for stem cell cultured),detected the second generation of MSCs'immunophenotypes(CD29, CD44

  6. Living with High Blood Pressure

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Living With High Blood Pressure If you have high blood pressure, the best thing to do is to talk ... help you track your blood pressure. Pregnancy Planning High blood pressure can cause problems for mother and baby. High ...

  7. Low White Blood Cell Count

    Science.gov (United States)

    Symptoms Low white blood cell count By Mayo Clinic Staff A low white blood cell count (leukopenia) is a decrease in disease-fighting cells ( ... a decrease in a certain type of white blood cell (neutrophil). The definition of low white blood cell ...

  8. Clinical significance of myeliod-derived suppressor cells in peripheral blood and serum interleukin-10 level detection in children with bronchiolitis%毛细支气管炎患儿外周血髓系抑制细胞及血清白细胞介素-10水平检测的意义

    Institute of Scientific and Technical Information of China (English)

    王秀芳; 雷瑞瑞; 张艳丽; 毕丹; 刘莹; 郭智兰; 韩影

    2013-01-01

    目的 检测毛细支气管炎患儿外周血髓系抑制细胞(MDSCs)占单个核细胞比例(MDSCs百分比)及血清IL-10水平,探讨其临床意义.方法 随机选取在郑州大学第三附属医院儿内科就诊的2岁以下毛细支气管炎患儿51例.其中男27例,女24例.分为特应质组(毛支Ⅰ组)(n=25)和非特应质组(毛支Ⅱ组)(n=26).同期随机选取郑州大学第三附属医院儿内科同年龄组外科疝气、肾结石等非感染性疾病术前患儿45例(无特应质疾病史及特应性疾病家族史)(其中男25例,女20例)作为对照组.抽取3组患儿静脉血4 mL,留取1 mL采用流式细胞术检测MDSCs;余3 mL留取血清标本,置-70℃冰箱保存,采用酶联免疫吸附法检测外周血IL-10水平.结果 1.各组患儿MDSCs百分比:毛支Ⅰ组[(3.17±0.24)%]、毛支Ⅱ组[(1.33±0.25)%]均高于对照组[(0.78±0.25)%](P均<0.01);毛支Ⅰ组MDSCs百分比高于毛支Ⅱ组,差异有统计学意义(P<0.01).2.各组患儿外周血IL-10水平比较:毛支Ⅰ组[(31.88 ±3.91) ng/L]、毛支Ⅱ组[(23.85 ±4.10) ng/L]均高于对照组[(13.63 ±2.83) ng/L](P均<0.01);毛支Ⅰ组外周血IL-10水平高于毛支Ⅱ组,差异有统计学意义(P<0.01).3.相关性分析:毛支Ⅰ组MDSCs百分比的分布趋势和血清IL-10水平呈正相关(r =0.717,P<0.01),毛支Ⅱ组、对照组MDSCs百分比与IL-10无相关性(r=0.262、-0.102,P均>0.05).结论 MDSCs通过上调IL-10水平在毛细支气管炎发展为哮喘的过程中起重要作用.%Objective To explore the clinical significance of detecting serum interleukin-10(IL-10) level and the proportion of myeloid-derived suppressor cells (MDSCs) in peripheral blood mononuclear cells (PBMCs) in children with bronchiolitis.Methods Fifty-one children with bronchiolitis less than 2 years old were randomly enrolled including 27 boys and 24 girls.They were divided into 2 groups:bronchiolitis group Ⅰ,25 children with atopic high risks were

  9. Inhibitory Effect of Human Umbilical Cord-derived Mesenchymal Stem Cells on Interleukin-17 Production in Peripheral Blood T Cells from Spondyloarthritis Patients%人脐带间充质干细胞对脊柱关节炎患者外周血T细胞产生IL-17的抑制作用

    Institute of Scientific and Technical Information of China (English)

    黄志芳; 朱剑; 吕双红; 张江林; 陈显达; 杜丽欣; 杨志岗; 宋亚昆; 吴东颖

    2013-01-01

    本研究通过观察人脐带间充质干细胞(hUCMSC)对脊柱关节炎(SpA)患者外周血T细胞产生IL-17的抑制作用,初步探索hUCMSC在SpA治疗领域的应用前景.体外分离SpA患者及健康志愿者外周血单个核细胞(PBMNC),PBMNC单独培养或与hUCMSC共培养,应用流式细胞仪检测T细胞中CD3+ CD4+ IL-17+(Th17)及CD3+ γδTCR+ IL-17+细胞比例;应用ELISA检测细胞培养上清中IL-17的浓度.结果表明,SpA患者外周血T细胞中Th17细胞占(3.42±0.82)%,CD3+ γδTCR+ IL-17+细胞占(0.30±0.10)%,分别是健康对照组(0.75±0.25)%和(0.06±0.02)%的4.5倍及5倍(P<0.01);SpA患者PBMNC与hUCMSC共培养后,T细胞中Th17细胞下降为(1.81±0.59)%,CD3+ γδTCR+ IL-17+细胞下降为(0.16±0.06)%(P<0.01);ELISA检测结果表明,SpA患者PBMNC培养上清IL-17的浓度显著高于健康对照组[(573.95±171.68) pg/ml vs(115.53±40.41) pg/ml (P<0.01)];SPA患者PBMNC与hUCMSC共培养后,细胞上清IL-17的浓度下降至(443.20±147.94) pg/ml(P<0.01).结论:hUCMSC能够抑制SpA患者外周血T细胞产生IL-17,在SpA临床治疗中具有应用前景.%In this study, the inhibitory effect of human umbilical cord-derived mesenchymal stem cells (hUCMSC) on interleukin-17(IL-17) production in peripheral blood T cells from patients with spondyloarthritis (SpA) were investigated, in order to explore the therapeutic potential of hUCMSC in the SpA. Peripheral blood mononuclear cells (PBMNC) were isolated from patients with SpA(n = 12) and healthy subjects(n =6). PBMNC were cultured in vitro with hUCMSC or alone. The expression of IL-17 in CD4+ T cells or γ/δ T cells were determined in each subject group by flow cytometry. IL-17 concentrations in PBMNC culture supernatantes were measured by ELISA. The results indicated that the proportion of IL-17-producing CD4+ T cells and IL-17-producing γ/δ T cells of SpA patients were 4.5 folds and 5 folds of healthy controls[CD3 +CD4+ IL-17+ cells (3.42 ±0

  10. SDF-1对糖尿病外周血EPCs功能的影响及其与PI3K/AKT信号通路的关系%Effects of Stromal Cell-Derived-Factor-1 on Endothelial Progenitor Cells of Peripheral Blood and Their Relationship with PI3K/AKT Signal Transduction Pathway in Patients with Diabetes

    Institute of Scientific and Technical Information of China (English)

    黎金凤; 林安华; 邓颖; 霍亚南; 刘精东; 吴明斌; 王晨秀

    2014-01-01

    Objective To observe the effects of stromal cell-derived-factor-1(SDF-1) on the function of endotheli⁃al progenitor cells(EPCs)of peripheral blood in patients with diabetes, and to discuss the effects of PI3K/AKT signaling path⁃way on the role of SDF-1 in EPCs. Methods The peripheral blood samples (30 mL) were collected in 10 diabetes patients (DM group) and 10 healthy controls (HC group). (1) The 100μg/L SDF-1 was added in intervention group. EGM-2MV was added in non-intervention group. The Boyden chamber and in vitro angiogenesis kit were used to analyze the migration and in vitro angiogenesis of EPCs. (2) Cultured EPCs were divided into blank control group, 1μg/L SDF-1 group, 10μg/L SDF-1 group, 100μg/L SDF-1 group, pure AMD3100 group and 100μg/L SDF-1+AMD3100 group. AKT protein expression lev⁃els of endothelial progenitor cells were detected by Western blot assay in each group. Results (1) Without intervention with SDF-1, EPCs’migration and angiogenesis ability were lower in DM group than those in HC group. After intervention with SDF-1, the migration and angiogenesis ability were enhanced in two groups, but the increased level was higher in DM group than that of HC group. (2) Under the same concentration, AKT protein expression level was significantly lower in DM group than that in HC group (P<0.01). AKT protein expression levels were increased with the increased levels of SDF-1 in DM group and HC group (P<0.05). AKT protein expression was significantly lower in 100μg/L SDF-1+AMD3100 group than that of 100μg/L SDF-1 group (P<0.05). Conclusion SDF-1 can increase the chemotactic migration and angiogenesis ability of EPCs in peripheral blood, especially for patients with diabetes. The effects of SDF-1 on EPCs were related to the PI3K/AKT signaling pathway.%目的:观察基质细胞衍生因子-1(SDF-1)对糖尿病外周血内皮祖细胞(EPCs)功能的影响,探讨SDF-1对EPCs的影响是否与PI3K/AKT信号通路有关。方法采集

  11. Blood: bone equilibrium

    Energy Technology Data Exchange (ETDEWEB)

    Neuman, M.W.

    1982-01-01

    The conundrum of blood undersaturation with respect to bone mineralization and its supersaturation with respect to bone's homeostatic function has acquired a new equation. On the supply side, Ca/sup 2 +/ is pumped in across bone cells to provide the needed Ca/sup 2 +/ x P/sub i/ for brushite precipitation. On the demand side, blood is in equilibrium with bone fluid, which is in equilibrium with a mineral more soluble than apatite. The function of potassium in this equation is yet to be found.

  12. Three new flavans in dragon's blood from Daemonorops draco.

    Science.gov (United States)

    Hao, Qian; Saito, Yoshinori; Matsuo, Yosuke; Li, Hai-Zhou; Takashi, Tanaka

    2015-01-01

    Three new flavans were isolated from chloroform extracts of dragon's blood from Daemonorops draco, together with eight known compounds. The structures of the new flavans were determined by 1D and 2D NMR spectroscopic analysis. These compounds are the first examples of 2-methoxyflavans from D. draco and regarded as derivatives of biogenetic intermediates from flavans to chalcones, which are characteristic of the dragon's blood.

  13. Manual versus automated blood sampling

    DEFF Research Database (Denmark)

    Teilmann, A C; Kalliokoski, Otto; Sørensen, Dorte B

    2014-01-01

    Facial vein (cheek blood) and caudal vein (tail blood) phlebotomy are two commonly used techniques for obtaining blood samples from laboratory mice, while automated blood sampling through a permanent catheter is a relatively new technique in mice. The present study compared physiological parameters......, glucocorticoid dynamics as well as the behavior of mice sampled repeatedly for 24 h by cheek blood, tail blood or automated blood sampling from the carotid artery. Mice subjected to cheek blood sampling lost significantly more body weight, had elevated levels of plasma corticosterone, excreted more fecal...... corticosterone metabolites, and expressed more anxious behavior than did the mice of the other groups. Plasma corticosterone levels of mice subjected to tail blood sampling were also elevated, although less significantly. Mice subjected to automated blood sampling were less affected with regard to the parameters...

  14. AN OVERVIEW ON BLOOD PURIFIER

    Directory of Open Access Journals (Sweden)

    Sabia Chauhan

    2013-09-01

    Full Text Available Blood is a connective tissue which protects us from different problems. Without blood body cannot functions at all and blood doesn’t purify itself. When blood does not purifies itself that times kidney, liver and lymphatic system work together that they help’s to purifiers the blood. Causes which are included in blood impurities are modern life style, junk food, alcohol etc. If the blood becomes impure it causes different problems e.g. acne, rashes, allergic etc. There is not any proper synthetic medication for blood impurities. Only herbal formulations are used for the blood purifier. In this review article we discussed about the market formulations and the different plants which are used in them with their different activities which are helpful in purifies the blood and also protects from other problems.

  15. Hepatites pós-transfusionais na cidade de Campinas, SP, Brasil: II. Presença dos anticorpos anti-HBc e anti-HCV em candidatos a doadores de sangue e ocorrência de hepatites pós-transfusionais pelo vírus C nos receptores de sangue ou derivados Post-transfusional hepatitis in the city of Campinas, SP, Brazil: II- Presence of anti-HBc and anti-HCV antibodies in blood donors and occurrence of post-transfusional hepatitis C virus in recipients of blood or derivates

    Directory of Open Access Journals (Sweden)

    Fernando Lopes Gonçales Júnior

    1993-02-01

    Full Text Available Pesquisamos os anticorpos anti-HBc e anti-HCV em amostras de soros provenientes de 799 candidatos a doadores, que tiveram suas unidades de sangue ou derivados transfundidas a 111 receptores. O anti-HBc e o anti-HCV foram reagentes, em respectivamente 9 e 2,1% dos doadores testados. Observamos que entre os 111 receptores, 44 haviam recebido pelo menos uma unidade anti-HBc positiva e 67 haviam sido transfundidos somente com unidades anti-HBc negativas. Houve um risco 4,5 vezes maior de aquisição de hepatite por vírus C pelos receptores que receberam pelo menos uma unidade anti-HBc positiva Se a pesquisa do anti-HBc fosse realizada na triagem sorológica dos doadores de sangue, cerca de 56% dos casos de HVC nos receptores saiam evitados. A população de receptores que recebeu pelo menos uma unidade anti-HCV reagente, apresentou um risco 29 vezes maior de adquirir esta hepatite, quando comparada aos receptores transfundidos com todas as unidades anti-HCV negativas. A realização do teste para a pesquisa do anti-HCV na triagem dos doadores de sangue, preveniria 79% dos casos de HVC pós-transfusionais. Os candidatos a doadores brasileiros parecem ser acometidos simultânea ou sequencialmente, pelos vírus B e C das hepatites, pois, 44,4% dos doadores anti-HCV positivos, também foram anti-HBc positivos. A realização dos testes para as pesquisas dos anticorpos anti-HBc e anti-HCV, nas triagens hemoterápicas, está indicada para prevenir a transmissão de hepatites pós-transfusionais, em nosso meio.We have analysed anti-HBc and anti-HCV antibodies in serum samples from 799 donors which had their blood or derivates transfused to 111 recipients. Anti-HBc and anti-HCV were reactive in respectively 9 and 2.1% of the donors tested. We have observed that among the 111 recipients, 44 had received at least one positive anti-HBc unit and 67 had been transfused only with negative anti-HBc, units. The risk of developing hepatitis C virus was 4.5 times

  16. Mechanical damage of red blood cells by rotary blood pumps: selective destruction of aged red blood cells and subhemolytic trauma.

    Science.gov (United States)

    Sakota, Daisuke; Sakamoto, Ryuki; Sobajima, Hideo; Yokoyama, Naoyuki; Waguri, Satoshi; Ohuchi, Katsuhiro; Takatani, Setsuo

    2008-10-01

    In this study, mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), and mean cell hemoglobin (MCH) were measured to quantify RBC damage by rotary blood pumps. Six-hour hemolysis tests were conducted with a Bio-pump BPX-80, a Sarns 15200 roller pump, and a prototype mag-lev centrifugal pump (MedTech Heart) using fresh porcine blood circulated at 5 L/min against a 100 mm Hg head pressure. The temperature of the test and noncirculated control blood was maintained at 37 degrees C. The normalized index of hemolysis (NIH) of each pump was determined by measuring the plasma-free hemoglobin level. The MCV was measured with a Coulter counter, and MCHC was derived from total hemoglobin and hematocrit. MCH was derived from MCV and MCHC. A multivariance statistical analysis (ANOVA) revealed statistically significant differences (n = 15, P < 0.05) in MCV, MCHC, and MCH between the blood sheared by the rotary blood pumps and the nonsheared control blood. Normalized to the control blood, the Bio-pump BPX-80 showed an MCV of 1.04 +/- 0.03, an MCHC of 0.95 +/- 0.04, and an MCH of 0.98 +/- 0.02; the mag-lev MedTech Heart had an MCV of 1.02 +/- 0.02, an MCHC of 0.97 +/- 0.02, and an MCH of 0.99 +/- 0.01; and the roller pump exhibited an MCV of 1.03 +/- 0.03, an MCHC of 0.96 +/- 0.03, and an MCH of 0.99 +/- 0.01. Per 0.01 increase in NIH, the BPX-80 showed a normalized MCV change of +10.1% and a normalized MCHC change of -14.0%; the MedTech Heart demonstrated a +6.9% MCV and -9.5% MCHC change; and the roller pump had a +0.5% MCV and -0.6% MCHC change. Due to shear in the pump circuits, the RBC increased while the MCHC decreased. The likely mechanism is that older RBCs with smaller size and higher hemoglobin concentration were destroyed fast by the shear, leaving younger RBCs with larger size and lower hemoglobin concentration. Subhemolytic trauma caused the intracellular hemoglobin to decrease due to gradual hemoglobin leakage through the micropores formed in the thinned

  17. A NEW FRACTAL DERIVATION

    OpenAIRE

    Ji-Huan He

    2011-01-01

    A new fractal derive is defined, which is very easy for engineering applications to discontinuous problems, two simple examples are given to elucidate to establish governing equations with fractal derive and how to solve such equations, respectively.

  18. Low Blood Pressure

    Science.gov (United States)

    ... Blood Pressure • Know Your Numbers • Understand Symptoms and Risks • Learn How HBP Can Harm Your Health • Make Changes That Matter • Find Tools & Resources Watch, Learn and Live Our Interactive Cardiovascular Library has detailed animations and illustrations to help you ...

  19. Hypertension (High Blood Pressure)

    Science.gov (United States)

    ... over the years led to verification of the important role of high blood pressure—especially in concert with ... is specific for that person will be an important key to improving prevention, ... an international team of investigators, funded in part by the NIH, ...

  20. Blood pressure and atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010319 Effects of combined application of Xuezhikang capsule with hypotensive drugs on arterial compliance and smoothness of the dynamic blood pressure. ZHU Zongtao(朱宗涛),et al. Dept Cardiol, Centr People’s Hosp, Tengzhou 277500.Chin J Integr Tradit & West Med 2010;30