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Sample records for cell msc paradigm

  1. Mesenchymal stem cell 1 (MSC1-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis.

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    Ruth S Waterman

    Full Text Available BACKGROUND: Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2. METHODOLOGY/PRINCIPAL FINDINGS: Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation. CONCLUSION/SIGNIFICANCE: These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease.

  2. TLR4 plays a crucial role in MSC-induced inhibition of NK cell function

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    Lu, Ying [No. 307 Hospital of the Chinese People' s Liberation Army, Beijing (China); Liu, Jin; Liu, Yang; Qin, Yaru [Beijing Institute of Radiation Medicine, Beijing (China); Luo, Qun [No. 307 Hospital of the Chinese People' s Liberation Army, Beijing (China); Wang, Quanli, E-mail: 13691110351@163.com [No. 307 Hospital of the Chinese People' s Liberation Army, Beijing (China); Duan, Haifeng, E-mail: duanhf0720@163.com [Beijing Institute of Radiation Medicine, Beijing (China)

    2015-08-21

    Mesenchymal stem cells (MSC) are a kind of stromal cell within the tumor microenvironment. In our research, MSC derived from acute myeloid leukemia patients' bone marrow (AML-MSC) and lung cancer tissues (LC-MSC) as well as normal bone marrow-derived MSC (BM-MSC) cultured in conditioned medium of HeLa cells were found to have higher expressions of Toll-like receptor (TLR4) mRNA compared with BM-MSC. The sorted TLR4-positive MSC (TLR4+ MSC) differed in cytokine (interleukin-6, interleukin-8, and monocyte chemoattractant protein-1) secretion from those of unsorted MSC. MSC was reported to inhibit natural killer (NK) cell proliferation and function. In this research, we confirmed that TLR4+ MSC aggravate this suppression. Furthermore, when TLR4 in the sorted cells were stimulated by LPS or following blocked by antibody, the suppression on NK cell proliferation and cytotoxicity were more intensive or recovered respectively. Compared to unsorted MSC, NKG2D receptor expression on NK cells were also inhibited by TLR4+ MSC. These findings suggest that activation of TLR4 pathway is important for TLR4+ MSC and MSC to obstruct anti-tumor immunity by inhibiting NK cell function, which may provide a potential stroma-targeted tumor therapy. - Highlights: • TLR4+ MSC inhibit NK cell proliferation in vivo and in vitro. • TLR4+ MSC inhibit NKG2D expression on NK cells and NK cell cytotoxicity. • The distinguished cytokine expression of TLR4+ MSC may contribute to the inhibition on NK cell function.

  3. A Transient Cell-shielding Method for Viable MSC Delivery Within Hydrophobic Scaffolds Polymerized in situ

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    2015-03-27

    A transient cell-shielding method for viable MSC delivery within hydrophobic scaffolds polymerized in situ Ruijing Guo a, b, Catherine L. Ward c...SUBTITLE A transient cell-shielding method for viable MSC delivery within hydrophobic scaffolds polymerized in situ 5a. CONTRACT NUMBER 5b. GRANT...To overcome cell death caused by reaction products from in situ polymerization , we encapsu- lated bone marrow-derived stem cells (BMSCs) in

  4. The Effect of Gender on Mesenchymal Stem Cell (MSC) Efficacy in Neonatal Hyperoxia-Induced Lung Injury

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    Sammour, Ibrahim; Somashekar, Santhosh; Huang, Jian; Batlahally, Sunil; Breton, Matthew; Valasaki, Krystalenia; Khan, Aisha; Wu, Shu

    2016-01-01

    Background Mesenchymal stem cells (MSC) improve alveolar and vascular structures in experimental models of bronchopulmonary dysplasia (BPD). Female MSC secrete more anti-inflammatory and pro-angiogenic factors as compared to male MSC. Whether the therapeutic efficacy of MSC in attenuating lung injury in an experimental model of BPD is influenced by the sex of the donor MSC or recipient is unknown. Here we tested the hypothesis that female MSC would have greater lung regenerative properties than male MSC in experimental BPD and this benefit would be more evident in males. Objective To determine whether intra-tracheal (IT) administration of female MSC to neonatal rats with experimental BPD has more beneficial reparative effects as compared to IT male MSC. Methods Newborn Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O2) from postnatal day (P) 2- P21 were randomly assigned to receive male or female IT bone marrow (BM)-derived green fluorescent protein (GFP+) MSC (1 x 106 cells/50 μl), or Placebo on P7. Pulmonary hypertension (PH), vascular remodeling, alveolarization, and angiogenesis were assessed at P21. PH was determined by measuring right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling was evaluated by quantifying the percentage of muscularized peripheral pulmonary vessels. Alveolarization was evaluated by measuring mean linear intercept (MLI) and radial alveolar count (RAC). Angiogenesis was determined by measuring vascular density. Data are expressed as mean ± SD, and analyzed by ANOVA. Results There were no significant differences in the RA groups. Exposure to hyperoxia resulted in a decrease in vascular density and RAC, with a significant increase in MLI, RVSP, and the percentage of partially and fully muscularized pulmonary arterioles. Administration of both male and female MSC significantly improved vascular density, alveolarization, RVSP, percent of muscularized vessels and alveolarization. Interestingly, the

  5. The use of multiparameter flow cytometry and cell sorting to characterize native human bone marrow mesenchymal stem cells (MSC).

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    Boxall, Sally; Jones, Elena

    2015-01-01

    This chapter describes a method for identification, phenotypic analysis, and cell sorting of rare mesenchymal stem cells (MSCs) from human bone marrow (BM) aspirates. The native BM MSC population is identified based on the CD45(-/low)CD271(+) phenotype. The method consists of three related procedures: Procedure 1 involves a microbead-based pre-enrichment step. Two other procedures describe direct flow cytometric analysis of MSCs following the isolation of the mononuclear cell (MNC) fraction (Procedure 2) or more rapidly, following a simple ammonium chloride-based red cell lysis (Procedure 3). Recently described multi-lineage transcript expression in the CD45(-/low)CD271(+) cells suggests that the native BM MSC fraction could be further subdivided into functionally distinct subpopulations. The present protocols are hoped to help MSC biologists to enter this exciting field of research and to take it forward towards a better understanding of MSC biology in vivo.

  6. Optimasi Penambahan Colcemid pada Karyotyping Kultur Mecenchymal Stem Cells (MSC Mencit

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    Ratih Rinendyaputri

    2016-02-01

    Full Text Available AbstractControl of the genetic stability of stem cells prior to the conduct of therapy is essential to prevent effects such as stem cell transformation. Karyotyping is a conventional technique to conduct an analysis of the number and structure of chromosomes. The analysis can only be performed on metaphase stage that needs to be optimized to get the cell at that stage because the length of the cell cycle are different in the each cell types. This study aims to obtain an optimal time to get MSC at metaphase stage. The study was conducted at the stem cell laboratory of Center for Biomedical and Basic Technology of Health. The event begins with isolation using flushing technique at the femur and tibia of mice. Furthermore, the culture in vitro and induction colcemid 0,25μg/ml for 8,16 and 24 hours to get the MSC at metaphase stage. KCl solution with a concentration of 0.075 M and 0,045 M used as a solvent hipotonis. Results showed that 16 hours of induction colcemid 0,25μg/ml in 0.075 M KCl solution usage percentage of MSC who are at metaphase stage and do the highest analysis (p<0.05. In this study 16 hours induction colcemid 0,25μg/ml is the optimal time to obtain metaphase stage of the MSC from bone marrow of mice.Keywords: mecenchymal stem cell, karyotyping, colcemidAbstrakKontrol terhadap stabilitas genetik pada sel punca sebelum pelaksanan terapi merupakan hal yang penting untuk mencegah efek seperti transformasi sel punca yang dapat terjadi. Secara konvensional dapat dilakukan karyotyping untuk melakukan analisis terhadap jumlah dan struktur kromosom. Analisis hanya dapat dilakukan pada tahap metafase sehingga perlu dilakukan optimasi untuk mendapatkan sel pada tahap tersebut mengingat panjang siklus sel setiap jenis sel berbeda. Penelitian ini bertujuan untuk memperoleh waktu yang optimal untuk mendapatkan MSC pada tahap metafase. Penelitian dilakukan di Laboratorium stem cell Pusat Biomedis dan Teknologi Dasar Kesehatan Badan Litbangkes

  7. Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC).

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    Giallongo, Cesarina; Tibullo, Daniele; Parrinello, Nunziatina L; La Cava, Piera; Di Rosa, Michelino; Bramanti, Vincenzo; Di Raimondo, Cosimo; Conticello, Concetta; Chiarenza, Annalisa; Palumbo, Giuseppe A; Avola, Roberto; Romano, Alessandra; Di Raimondo, Francesco

    2016-12-27

    Granulocytic-Myeloid-derived suppressor cells (G-MDSC) are increased in Multiple Myeloma (MM) patients but the mechanisms of G-MDSC generation are still unknown. There are many evidences of the role of mesenchymal stem cells (MSC) in promoting MM cell growth, survival and drug-resistance. We here used a specific experimental model in vitro to evaluate the ability of MSC to induce G-MDSC. We found that although MSC derived from healthy donors (HD), MGUS and MM were able to generate the same amount of MDSC, only MM-MSC-educated G-MDSC exhibited suppressive ability. In addition, in comparison with MSC derived from HD, MM-MSC produce higher amount of immune-modulatory factors that could be involved in MDSC induction. Compared to G-MDSC obtained from co-culture models with MSC from healthy subjects, both MGUS and MM-MSC-educated G-MDSC showed increase of immune-modulatory factors. However, only MM-MSC educated G-MDSC 1) up-regulated immune-suppressive factors as ARG1 and TNFα, 2) expressed higher levels of PROK2, important in angiogenesis and inflammatory process, and 3) showed ability to digest bone matrix.Our data demonstrate that MM-MSC are functionally different from healthy subjects and MGUS-MSC, supporting an evolving concept regarding the contribution of MM-MSC to tumor development and progression.

  8. The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood.

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    Zeddou, Mustapha; Briquet, Alexandra; Relic, Biserka; Josse, Claire; Malaise, Michel G; Gothot, André; Lechanteur, Chantal; Beguin, Yves

    2010-07-01

    Many studies have drawn attention to the emerging role of MSC (mesenchymal stem cells) as a promising population supporting new clinical concepts in cellular therapy. However, the sources from which these cells can be isolated are still under discussion. Whereas BM (bone marrow) is presented as the main source of MSC, despite the invasive procedure related to this source, the possibility of isolating sufficient numbers of these cells from UCB (umbilical cord blood) remains controversial. Here, we present the results of experiments aimed at isolating MSC from UCB, BM and UCM (umbilical cord matrix) using different methods of isolation and various culture media that summarize the main procedures and criteria reported in the literature. Whereas isolation of MSC were successful from BM (10:10) and (UCM) (8:8), only one cord blood sample (1:15) gave rise to MSC using various culture media [DMEM (Dulbecco's modified Eagle's medium) +5% platelet lysate, DMEM+10% FBS (fetal bovine serum), DMEM+10% human UCB serum, MSCGM] and different isolation methods [plastic adherence of total MNC (mononuclear cells), CD3+/CD19+/CD14+/CD38+-depleted MNC and CD133+- or LNGFR+-enriched MNC]. MSC from UCM and BM were able to differentiate into adipocytes, osteocytes and hepatocytes. The expansion potential was highest for MSC from UCM. The two cell populations had CD90+/CD73+/CD105+ phenotype with the additional expression of SSEA4 and LNGFR for BM MSC. These results clearly exclude UCB from the list of MSC sources for clinical use and propose instead UCM as a rich, non-invasive and abundant source of MSC.

  9. Cell therapy medicinal product regulatory framework in Europe and its application for MSC based therapy development

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    Janis eAncans

    2012-08-01

    Full Text Available Advanced therapy medicinal products (ATMPs, including cell therapy products, form a new class of medicines in the European Union. Since ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT has been established at European Medicines Agency (EMA for centralized classification, certification and evaluation procedures, and other ATMP related tasks. Guidance documents, initiatives and interaction platforms are available to make the new framework more accessible for small and medium-sized enterprises, academia, hospitals and foundations. Good understanding of centralised and national components of the regulatory system is required to plan product development. It is in the best interests of cell therapy developers to utilise provided resources starting with the preclinical stage. Whilst there have not been mesenchymal stem cell (MSC based medicine authorisations in the EU, three MSC products have received marketing approval in other regions since 2011. Information provided on regulatory requirements, procedures and initiatives is aimed to facilitate MSC based medicinal product development and authorisation in the EU.

  10. Mesenchymal Stem Cells (MSC Regulate Activation of Granulocyte-Like Myeloid Derived Suppressor Cells (G-MDSC in Chronic Myeloid Leukemia Patients.

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    Cesarina Giallongo

    Full Text Available It is well known that mesenchymal stem cells (MSC have a role in promotion of tumor growth, survival and drug-resistance in chronic myeloid leukemia (CML. Recent reports indicated that a subpopulation of myeloid cells, defined as granulocyte-like myeloid-derived suppressor cells (G-MDSC is increased in these patients. So far, the role of MSC in MDSC expansion and activation into the BM microenvironment remains unexplored. To address this question, here we use a specific experimental model in vitro, co-culturing MSC with peripheral blood mononucleated cells (PBMC from normal individuals, in order to generate MSC-educated G-MDSC. Although MSC of healthy donors (HD and CML patients were able to generate the same amount of MDSC, only CML-MSC-educated G-MDSC exhibited suppressive ability on autologous T lymphocytes. In addition, compared with HD-MSC, CML-MSC over-expressed some immunomodulatory factors including TGFβ, IL6 and IL10, that could be involved in MDSC activation. CML-MSC-educated G-MDSC expressed higher levels of ARG1, TNFα, IL1β, COX2 and IL6 than G-MDSC isolated from co-culture with HD-MSC. Our data provide evidence that CML-MSC may play a critical role in tumor microenvironment by orchestrating G-MDSC activation and regulating T lymphocytes-mediated leukemia surveillance, thus contributing to CML immune escape.

  11. [Nuclear heterogeneity and proliferative capacity of human adipose derived MSC-like cells].

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    Lavrov, A V; Smirnichina, S A

    2010-01-01

    Adipose derived stem cells (ADSCs) are MSC-like cells which could be easily used for regenerative medicine. Here, the morphology and proliferative capacity of human ADSCs is discribed. ADSCs were analyzed after one month of cultivation at a density of 10 cells/cm2. 21 colonies were counted. Few atypical cells (huge nuclei and cytoplasm) were found in 9 out of 17 colonies analyzed. ANOVA demonstrated that colonies also differed (P = 0.0025) in nuclei dimensions and scatter in the dimensions in each colony. Nuclei dimensions and cell density logarithms correlated in reverse proportion (-0.7; P = 0.002). Thus, ADSCs were heterogeneous and represented two types of cells: small highly proliferative and large low proliferative cells. Cell heterogeneity observed in some colonies might be due to cells registered at different cell cycle phases. Stable and typical morphology, colony-formation capability and high proliferative capacity of cells indicate visceral adipose tissue as a rich source of ADSCs.

  12. Suicide gene reveals the myocardial neovascularization role of mesenchymal stem cells overexpressing CXCR4 (MSC(CXCR4.

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    Jialiang Liang

    Full Text Available BACKGROUND: Our previous studies indicated that MSC(CXCR4 improved cardiac function after myocardial infarction (MI. This study was aimed to investigate the specific role of MSC(CXCR4 in neovascularization of infarcted myocardium using a suicide gene approach. METHODS: MSCs were transduced with either lentivirus-null vector/GFP (MSC(Null as control or vector encoding for overexpressing CXCR4/GFP. The MSC derived-endothelial cell (EC differentiation was assessed by a tube formation assay, Dil-ac-LDL uptake, EC marker expression, and VE-cadherin promoter activity assay. Gene expression was analyzed by quantitative RT-PCR or Western blot. The suicide gene approach was under the control of VE-cadherin promoter. In vivo studies: Cell patches containing MSC(Null or MSC(CXCR4 were transduced with suicide gene and implanted into the myocardium of MI rat. Rats received either ganciclovir (GCV or vehicle after cell implantation. After one month, the cardiac functional changes and neovascularization were assessed by echocardiography, histological analysis, and micro-CT imaging. RESULTS: The expression of VEGF-A and HIF-1α was significantly higher in MSC(CXCR4 as compared to MSC(Null under hypoxia. Additionally, MSC(CXCR4 enhanced new vessel formation and EC differentiation, as well as STAT3 phosphorylation under hypoxia. STAT3 participated in the transcription of VE-cadherin in MSC(CXCR4 under hypoxia, which was inhibited by WP1066 (a STAT3 inhibitor. In addition, GCV specifically induced death of ECs with suicide gene activation. In vivo studies: MSC(CXCR4 implantation promoted cardiac functional restoration, reduced infarct size, improved cardiac remodeling, and enhanced neovascularization in ischemic heart tissue. New vessels derived from MSC(CXCR4 were observed at the injured heart margins and communicated with native coronary arteries. However, the derived vessel networks were reduced by GCV, reversing improvement of cardiac function. CONCLUSION: The

  13. Novel isolation strategy to deliver pure fetal-origin and maternal-origin mesenchymal stem cell (MSC) populations from human term placenta.

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    Patel, J; Shafiee, A; Wang, W; Fisk, N M; Khosrotehrani, K

    2014-11-01

    The placenta is an abundant source of mesenchymal stem/stromal cells (MSC). Although presumed of translationally-advantageous fetal origin, the literature instead suggests a high incidence of either contaminating or pure maternal MSC. Despite definitional criteria that MSC are CD34-, increasing evidence suggests that fetal MSC may be CD34 positive in vivo. We flow sorted term placental digests based on CD34+ expression and exploited differential culture media to isolate separately pure fetal and maternal MSC populations. This method has considerable translational implications, in particular to clinical trials underway with "placental" MSC of uncertain or decidual origin.

  14. Right ventricular effects of intracoronary delivery of mesenchymal stem cells (MSC) in an animal model of pressure overload heart failure.

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    Molina, Ezequiel J; Palma, Jon; Gupta, Dipin; Gaughan, John P; Houser, Steven; Macha, Mahender

    2009-12-01

    In a rat model of left ventricular pressure overload hypertrophy with biventricular failure, we studied the effects of intracoronary delivery of mesenchymal stem cells (MCS) upon right ventricular hemodynamic performance, profiles of local inflammation and apoptosis, and determinants of extracellular matrix remodeling. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After a decrease in left ventricular fractional shortening of 25% from the baseline (relative 50% reduction), animals were randomized to an intracoronary injection of MSC (n=28) or PBS (n=20). Right ventricular hemodynamic assessment and measurement of local inflammatory markers, proapoptotic factors, and determinants of extracellular matrix remodeling were performed on post-transplantation day 7, 14, 21 or 28. MSC injection improved right ventricular systolic function in the MSC group compared to the control group (mean+/-SD, max dP/dt 772+/-272 mm Hg/s vs. 392+/-132 at 28 days, PRight ventricular levels of IL-1, IL-6, TNF-alpha, bax, bak and p38 were significantly decreased in the MSC treated animals. Expression of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3 declined in the MSC group compared with controls after 28 days. In this model of left ventricular pressure overload hypertrophy and biventricular failure, intracoronary delivery of MSC was associated with an improvement in the right ventricular hemodynamic performance, profiles of local inflammation and apoptosis, and determinants of extracellular matrix remodeling.

  15. The histopathology of a human mesenchymal stem cell experimental tumor model: support for an hMSC origin for Ewing's sarcoma?

    DEFF Research Database (Denmark)

    Burns, J S; Abdallah, B M; Schrøder, Henrik Daa

    2008-01-01

    -forming potential of early passage hMSC-TERT20 cells, tumors derived from late passage cells expressed early biomarkers of osteogenesis. However, hMSC-TERT20 cells were heterogeneous for alpha smooth muscle actin (ASMA) expression and one out of six hMSC-TERT20 derived single cell clones was strongly ASMA positive....... Tumors from this ASMA+ clone had distinctive vascular qualities with hot spots of high CD34+ murine endothelial cell density, together with CD34- regions with a branching periodic acid Schiff reaction pattern. Such clone-specific differences in host vascular response provide novel models to explore...

  16. Cell therapy medicinal product regulatory framework in Europe and its application for MSC-based therapy development.

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    Ancans, Janis

    2012-01-01

    Advanced therapy medicinal products (ATMPs), including cell therapy products, form a new class of medicines in the European Union. Since the ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT) has been established at the European Medicines Agency (EMA) for centralized classification, certification and evaluation procedures, and other ATMP-related tasks. Guidance documents, initiatives, and interaction platforms are available to make the new framework more accessible for small- and medium-sized enterprises, academia, hospitals, and foundations. Good understanding of the centralized and national components of the regulatory system is required to plan product development. It is in the best interests of the cell therapy developers to utilize the resources provided starting with the pre-clinical stage. Whilst there have been no mesenchymal stem cell (MSC)-based medicine authorizations in the EU, three MSC products have received marketing approval in other regions since 2011. The information provided on the regulatory requirements, procedures, and initiatives is aimed at facilitating MSC-based medicinal product development and authorization in the EU.

  17. Hypoxia pretreatment and EPO-modification enhance the protective effects of MSC on neuron-like PC12 cells in a similar way.

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    Feng, Jinli; Wang, Wei

    2017-01-08

    Mesenchymal stem cells (MSC) based cell transplantation therapy is proved to be an attractive strategy with great potential for improvement of hypoxia induced neural damage. In the present study, MSCs were co-culture with PC12 to investigate its protective effects against hypoxia pretreatment, and the Lactate dehydrogenase (LDH) release assay, MTT and Anexin V staining were performed to analysis the cellular damage or apoptotic. RT-PCR and Western blotting were further used to investigate the underlying mechanism. The results indicate that hypoxia treatment results in the decrease of PC12 cell viability, yet co-culture with MSC could protect the PC12 from hypoxia induced damage. Hypoxia pre-activated or EPO transduced MSC with up-regulated erythropoietin (EPO) expression could further enhance MSC's protective effect against hypoxia induced cell damage, which was associated with high level of anti-apoptotic p-Akt and ration Bcl-2/Bax, and decreased Caspase 3 in PC12. Taken together, these data suggests high levels of MSC-mediated cyto-protection is closely tied to high gene expression levels of EPO. The up-regulation of EPO for enhanced MSC-mediated cyto-protection may has great potential for the MSC cellular therapy of neural or neuronal injuries induced by hypoxia.

  18. Therapeutic effect of transplanted human Wharton's jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) in an animal model of multiple sclerosis.

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    Mikaeili Agah, Elmira; Parivar, Kazem; Joghataei, Mohammad Taghi

    2014-04-01

    Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). A potential new therapeutic approach for MS is cell transplantation which may promote remyelination. We transplanted human Wharton's jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) into the brain ventricles of mice induced with experimental autoimmune encephalomyelitis (EAE), the animal model of MS. We studied the effect of the transplanted OPCs on the functional and pathological manifestations of the disease. Transplanted hWJ-MSC-derived OPCs significantly reduced the clinical signs of EAE. Histological examinations showed that remyelination was significantly increased after transplantation. These results suggest that hWJ-MSC-derived OPCs promote the regeneration of myelin sheaths in the brain.

  19. Life behind cell walls: paradigm lost, paradigm regained.

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    Lamport, D T

    2001-09-01

    This review of the living cell wall and its protein components is in two parts. The first is anecdotal. A personal account spanning over 40 years research may perhaps be an antidote to one stereotypical view of scientists as detached and humorless. The second part deals with the meaning of function, particularly as it applies to hydroxyproline-rich glycoproteins. Function is a difficult word to define objectively. However, with help from such luminaries as Humpty Dumpty: "A word means what I want it to mean, neither more nor less," and Wittgenstein: "Giving examples of usage ... is the only way to talk about meaning," it is possible to construct a ziggurat representing increasingly complex levels of organization from molecular structure to ecology. Forty years ago I suggested that hydroxyproline-rich structural proteins played a key role in cell wall functioning. But because the bulk of the wall is carbohydrate, there has been an understandable resistance to paradigm change. Expansins, paradoxically, contribute greatly to this resistance because their modus operandi as cell-wall-loosening proteins is based on the idea that they break hydrogen bonds between polysaccharide chains allowing slippage. However, this view is not consistent with the recent discovery [Grobe et al. (1999) Eur. J. Biochem 263: 33-40] that beta-expansins may be proteases, as it implies that the extensin network is not a straightjacket but a substrate for expansin in muro. Such a direct role for extensins in both negative and positive regulation of cell expansion and elongation may constitute a major morphogenetic mechanism operating at all levels of plant growth and development.

  20. Differential MSC activation leads to distinct mononuclear leukocyte binding mechanisms

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    Kota, Daniel J.; Dicarlo, Bryan; Hetz, Robert A.; Smith, Philippa; Cox, Charles S.; Olson, Scott D.

    2014-04-01

    Advances in the field of Multipotent Mesenchymal Stromal cell (MSC) biology have demonstrated that MSCs can improve disease outcome when `activated' to exert immunomodulatory effects. However, the precise mechanisms modulating MSC-immune cells interactions remain largely elusive. In here, we activated MSC based on a recent polarization paradigm, in which MSCs can be polarized towards a pro- or anti-inflammatory phenotype depending on the Toll-like receptor stimulated, to dissect the mechanisms through which MSCs physically interact with and modulate leukocytes in this context. Our data show that MSCs activated through the Toll-like receptor (TLR) 4 pathway increased VCAM-1 and ICAM-1 dependent binding of leukocytes. On the other hand, TLR3 stimulation strongly increases leukocytes affinity to MSC comparatively, through the formation of cable-like hyaluronic acid structures. In addition, TLR4 activation elicited secretion of pro-inflammatory mediators by MSCs, whereas TLR3-activated MSCs displayed a milder pro-inflammatory phenotype, similar to inactivated MSCs. However, the differently activated MSCs maintained their ability to suppress leukocyte activation at similar levels in our in vitro model, and this immunomodulatory property was shown here to be partially mediated by prostaglandin. These results reinforce the concept that alternate activation profiles control MSC responses and may impact the therapeutic use of MSCs.

  1. Therapeutic potential of mesenchymal stromal cells and MSC conditioned medium in Amyotrophic Lateral Sclerosis (ALS--in vitro evidence from primary motor neuron cultures, NSC-34 cells, astrocytes and microglia.

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    Hui Sun

    Full Text Available Administration of mesenchymal stromal cells (MSC improves functional outcome in the SOD1G93A mouse model of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS as well as in models of other neurological disorders. We have now investigated the effect of the interaction between MSC and motor neurons (derived from both non-transgenic and mutant SOD1G93A transgenic mice, NSC-34 cells and glial cells (astrocytes, microglia (derived again from both non-transgenic and mutant SOD1G93A ALS transgenic mice in vitro. In primary motor neurons, NSC-34 cells and astrocytes, MSC conditioned medium (MSC CM attenuated staurosporine (STS - induced apoptosis in a concentration-dependent manner. Studying MSC CM-induced expression of neurotrophic factors in astrocytes and NSC-34 cells, we found that glial cell line-derived neurotrophic factor (GDNF and ciliary neurotrophic factor (CNTF gene expression in astrocytes were significantly enhanced by MSC CM, with differential responses of non-transgenic and mutant astrocytes. Expression of Vascular Endothelial Growth Factor (VEGF in NSC-34 cells was significantly upregulated upon MSC CM-treatment. MSC CM significantly reduced the expression of the cytokines TNFα and IL-6 and iNOS both in transgenic and non-transgenic astrocytes. Gene expression of the neuroprotective chemokine Fractalkine (CX3CL1 was also upregulated in mutant SOD1G93A transgenic astrocytes by MSC CM treatment. Correspondingly, MSC CM increased the respective receptor, CX3CR1, in mutant SOD1G93A transgenic microglia. Our data demonstrate that MSC modulate motor neuronal and glial response to apoptosis and inflammation. MSC therefore represent an interesting candidate for further preclinical and clinical evaluation in ALS.

  2. Cellular Kinetics of Perivascular MSC Precursors

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    William C. W. Chen

    2013-01-01

    Full Text Available Mesenchymal stem/stromal cells (MSCs and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.

  3. Quantification of Mesenchymal Stem Cell (MSC delivery to a target site using in vivo confocal microscopy.

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    Luke J Mortensen

    Full Text Available The ability to deliver cells to appropriate target tissues is a prerequisite for successful cell-based therapy. To optimize cell therapy it is therefore necessary to develop a robust method of in vivo cell delivery quantification. Here we examine Mesenchymal Stem Cells (MSCs labeled with a series of 4 membrane dyes from which we select the optimal dye combination for pair-wise comparisons of delivery to inflamed tissue in the mouse ear using confocal fluorescence imaging. The use of an optimized dye pair for simultaneous tracking of two cell populations in the same animal enables quantification of a test population that is referenced to an internal control population, thereby eliminating intra-subject variations and variations in injected cell numbers. Consistent results were obtained even when the administered cell number varied by more than an order of magnitude, demonstrating an ability to neutralize one of the largest sources of in vivo experimental error and to greatly reduce the number of cells required to evaluate cell delivery. With this method, we are able to show a small but significant increase in the delivery of cytokine pre-treated MSCs (TNF-α & IFN-γ compared to control MSCs. Our results suggest future directions for screening cell strategies using our in vivo cell delivery assay, which may be useful to develop methods to maximize cell therapeutic potential.

  4. Cytoplasmic Domain of MscS Interacts with Cell Division Protein FtsZ: A Possible Non-Channel Function of the Mechanosensitive Channel in Escherichia Coli.

    Directory of Open Access Journals (Sweden)

    Piotr Koprowski

    Full Text Available Bacterial mechano-sensitive (MS channels reside in the inner membrane and are considered to act as emergency valves whose role is to lower cell turgor when bacteria enter hypo-osmotic environments. However, there is emerging evidence that members of the Mechano-sensitive channel Small (MscS family play additional roles in bacterial and plant cell physiology. MscS has a large cytoplasmic C-terminal region that changes its shape upon activation and inactivation of the channel. Our pull-down and co-sedimentation assays show that this domain interacts with FtsZ, a bacterial tubulin-like protein. We identify point mutations in the MscS C-terminal domain that reduce binding to FtsZ and show that bacteria expressing these mutants are compromised in growth on sublethal concentrations of β-lactam antibiotics. Our results suggest that interaction between MscS and FtsZ could occur upon inactivation and/or opening of the channel and could be important for the bacterial cell response against sustained stress upon stationary phase and in the presence of β-lactam antibiotics.

  5. Cytoplasmic Domain of MscS Interacts with Cell Division Protein FtsZ: A Possible Non-Channel Function of the Mechanosensitive Channel in Escherichia Coli.

    Science.gov (United States)

    Koprowski, Piotr; Grajkowski, Wojciech; Balcerzak, Marcin; Filipiuk, Iwona; Fabczak, Hanna; Kubalski, Andrzej

    2015-01-01

    Bacterial mechano-sensitive (MS) channels reside in the inner membrane and are considered to act as emergency valves whose role is to lower cell turgor when bacteria enter hypo-osmotic environments. However, there is emerging evidence that members of the Mechano-sensitive channel Small (MscS) family play additional roles in bacterial and plant cell physiology. MscS has a large cytoplasmic C-terminal region that changes its shape upon activation and inactivation of the channel. Our pull-down and co-sedimentation assays show that this domain interacts with FtsZ, a bacterial tubulin-like protein. We identify point mutations in the MscS C-terminal domain that reduce binding to FtsZ and show that bacteria expressing these mutants are compromised in growth on sublethal concentrations of β-lactam antibiotics. Our results suggest that interaction between MscS and FtsZ could occur upon inactivation and/or opening of the channel and could be important for the bacterial cell response against sustained stress upon stationary phase and in the presence of β-lactam antibiotics.

  6. Enhancement of cell adhesion, retention, and survival of HUVEC/cbMSC aggregates that are transplanted in ischemic tissues by concurrent delivery of an antioxidant for therapeutic angiogenesis.

    Science.gov (United States)

    Huang, Chieh-Cheng; Pan, Wen-Yu; Tseng, Michael T; Lin, Kun-Ju; Yang, Yi-Pei; Tsai, Hung-Wen; Hwang, Shiaw-Min; Chang, Yen; Wei, Hao-Ji; Sung, Hsing-Wen

    2016-01-01

    A recurring obstacle in cell-base strategies for treating ischemic diseases is the significant loss of viable cells that is caused by the elevated levels of regional reactive oxygen species (ROS), which ultimately limits therapeutic capacity. In this study, aggregates of human umbilical vein endothelial cells (HUVECs) and cord-blood mesenchymal stem cells (cbMSCs), which are capable of inducing therapeutic angiogenesis, are prepared. We hypothesize that the concurrent delivery of an antioxidant N-acetylcysteine (NAC) may significantly increase cell retention following the transplantation of HUVEC/cbMSC aggregates in a mouse model with hindlimb ischemia. Our in vitro results demonstrate that the antioxidant NAC can restore ROS-impaired cell adhesion and recover the reduced angiogenic potential of HUVEC/cbMSC aggregates under oxidative stress. In the animal study, we found that by scavenging the ROS generated in ischemic tissues, NAC is likely to be able to establish a receptive cell environment in the early stage of cell transplantation, promoting the adhesion, retention, and survival of cells of engrafted aggregates. Therapeutic angiogenesis is therefore enhanced and blood flow recovery and limb salvage are ultimately achieved. The combinatory strategy that uses an antioxidant and HUVEC/cbMSC aggregates may provide a new means of boosting the therapeutic efficacy of cell aggregates for the treatment of ischemic diseases.

  7. Adult Cardiac-Resident MSC-like Stem Cells with a Proepicardial Origin

    NARCIS (Netherlands)

    Chong, James J. H.; Chandrakanthan, Vashe; Xaymardan, Munira; Asli, Naisana S.; Li, Joan; Ahmed, Ishtiaq; Heffernan, Corey; Menon, Mary K.; Scarlett, Christopher J.; Rashidianfar, Amirsalar; Biben, Christine; Zoellner, Hans; Colvin, Emily K.; Pimanda, John E.; Biankin, Andrew V.; Zhou, Bin; Pu, William T.; Prall, Owen W. J.; Harvey, Richard P.

    2011-01-01

    Colony-forming units fibroblast (CFU-Fs), analogous to those giving rise to bone marrow (BM) mesenchymal stem cells (MSCs), are present in many organs, although the relationship between BM and organ-specific CFU-Fs in homeostasis and tissue repair is unknown. Here we describe a population of adult c

  8. A critical role of IFNγ in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Bone-marrow-derived mesenchymal stem cells (MSCs) have been shown to possess immunosuppressive properties, e.g., by inhibiting T cell proliferation. Activated T cells can also enhance the immunosuppression ability of MSCs. The precise mechanisms underlying MSC-mediated immunosuppression remain largely undefined, although both cell-cell contact and soluble factors have been implicated; nor is it clear how the immunosuppressive property of MSCs is modulated by T cells. Using MSCs isolated from mouse bone marrow, we show here that interferon gamma (IFNγ), a well-known proinflammatory cytokine produced by activated T cells, plays an important role in priming the immunosuppressive property of MSCs. Mechanistically, IFNγ acts directly on MSCs and leads to up-regulation of B7-H1, an inhibitory surface molecule in these stem cells. MSCs primed by activated T cells derived from IFNγ-/- mouse exhibited dramatically reduced ability to suppress T cell proliferation, a defect that can be rescued by supplying exogenous IFNy. Moreover, siRNA-mediated knockdown of B7-H1 in MSCs abolished immunosuppression by these cells. Taken together, our results suggest that IFNy plays a critical role in triggering the immunosuppresion by MSCs through upregulating B7-H1 in these cells, and provide evidence supporting the cell-cell contact mechanism in MSC-mediated immunosuppression.

  9. Electrostatics at the membrane define MscL channel mechanosensitivity and kinetics.

    Science.gov (United States)

    Zhong, Dalian; Blount, Paul

    2014-12-01

    The bacterial mechanosensitive channel of large conductance (MscL) serves as a biological emergency release valve, preventing the occurrence of cell lysis caused by acute osmotic stress. Its tractable nature allows it to serve as a paradigm for how a protein can directly sense membrane tension. Although much is known of the importance of the hydrophobicity of specific residues in channel gating, it has remained unclear whether electrostatics at the membrane plays any role. We studied MscL chimeras derived from functionally distinct orthologues: Escherichia coli and Staphylococcus aureus. Dissection of one set led to an observation that changing the charge of a single residue, K101, of E. coli (Ec)-MscL, effects a channel phenotype: when mutated to a negative residue, the channel is less mechanosensitive and has longer open dwell times. Assuming electrostatic interactions, we determined whether they are due to protein-protein or protein-lipid interactions by performing site-directed mutagenesis elsewhere in the protein and reconstituting channels into defined lipids, with and without negative head groups. We found that although both interactions appear to play some role, the primary determinant of the channel phenotype seems to be protein-lipid electrostatics. The data suggest a model for the role of electrostatic interactions in the dynamics of MscL gating.

  10. Deep tissue single cell MSC ablation using a fiber laser source to evaluate therapeutic potential in osteogenesis imperfecta

    Science.gov (United States)

    Tehrani, Kayvan F.; Pendleton, Emily G.; Lin, Charles P.; Mortensen, Luke J.

    2016-04-01

    Osteogenesis imperfecta (OI) is a currently uncurable disease where a mutation in collagen type I yields brittle bones. One potential therapy is transplantation of mesenchymal stem cells (MSCs), but controlling and enhancing transplanted cell survival has proven challenging. Therefore, we use a 2- photon imaging system to study individual transplanted cells in the living bone marrow. We ablated cells deep in the bone marrow and observed minimal collateral damage to surrounding tissue. Future work will evaluate the local impact of transplanted MSCs on bone deposition in vivo.

  11. Scanning MscL Channels with Targeted Post-Translational Modifications for Functional Alterations.

    Directory of Open Access Journals (Sweden)

    Irene Iscla

    Full Text Available Mechanosensitive channels are present in all living organisms and are thought to underlie the senses of touch and hearing as well as various important physiological functions like osmoregulation and vasoregulation. The mechanosensitive channel of large conductance (MscL from Escherichia coli was the first protein shown to encode mechanosensitive channel activity and serves as a paradigm for how a channel senses and responds to mechanical stimuli. MscL plays a role in osmoprotection in E. coli, acting as an emergency release valve that is activated by membrane tension due to cell swelling after an osmotic down-shock. Using an osmotically fragile strain in an osmotic down-shock assay, channel functionality can be directly determined in vivo. In addition, using thiol reagents and expressed MscL proteins with a single cysteine substitution, we have shown that targeted post-translational modifications can be performed, and that any alterations that lead to dysfunctional proteins can be identified by this in vivo assay. Here, we present the results of such a scan performed on 113 MscL cysteine mutants using five different sulfhydryl-reacting probes to confer different charges or hydrophobicity to each site. We assessed which of these targeted modifications affected channel function and the top candidates were further studied using patch clamp to directly determine how channel activity was affected. This comprehensive screen has identified many residues that are critical for channel function as well as highlighted MscL domains and residues that undergo the most drastic environmental changes upon gating.

  12. Comparison of Hyclone and Biow: Effect to hMSC Proliferation, Morphology, and Osteogenic Differentiationest

    OpenAIRE

    Tania Saskianti; Kanawa Misami; Yukio Kato

    2013-01-01

    Mesenchymal stem cells (MSC) are expanded in a basal culture medium supplemented with fetal bovine serum (FBS) with or without additional growth factors. The serum contains basic components such as hormones and growth factors which provide robust MSC proliferation. However, the effects of different serum in the isolation and proliferation of primary MSC remains unclear. In this study we compared effect of serums on stimulating MSC proliferation and osteogenic differentiation. Therefore we eva...

  13. Comparison of Hyclone and Biow: Effect to hMSC Proliferation, Morphology, and Osteogenic Differentiationest

    Directory of Open Access Journals (Sweden)

    Tania Saskianti

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSC are expanded in a basal culture medium supplemented with fetal bovine serum (FBS with or without additional growth factors. The serum contains basic components such as hormones and growth factors which provide robust MSC proliferation. However, the effects of different serum in the isolation and proliferation of primary MSC remains unclear. In this study we compared effect of serums on stimulating MSC proliferation and osteogenic differentiation. Therefore we evaluated the impact of Hyc1 and Bw1 containing medium on primary MSC morphology. Primary MSC grown in both serum containing medium retain the ability to differentiate into osteoblast. Bw1 containing serum showed slightly, unsignificanty higher potential as compared to Hyc1. However more detailed analysis on the composition of each serum on overall MSC morphology and proliferation must be further explored. The result of this study should form a basis for further studies examining specific substance needed in MSC proliferation and differentiation in more detail.

  14. Analysis list: MSC [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available MSC Digestive tract + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/MSC....1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/MSC.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/MSC....10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/MSC.Digestive_tract.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Digestive_tract.gml ...

  15. Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro.

    Science.gov (United States)

    Scherzad, Agmal; Hackenberg, Stephan; Froelich, Katrin; Rak, Kristen; Hagen, Rudolf; Taeger, Johannes; Bregenzer, Maximillian; Kleinsasser, Norbert

    2016-03-01

    Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induces genotoxic effects. Bone marrow MSC were treated with low-dose salinomycin (100 nM) (MSC-Sal) for 4 weeks, while the medium containing salinomycin was changed every other day. Functional changes were evaluated and compared to MSC without salinomycin treatment (MSC-control). MSC-Sal and MSC-control were positive for cluster of differentiation 90 (CD90), CD73 and CD44, and negative for CD34. There were no differences observed in cell morphology or cytoskeletal structures following salinomycin exposure. The differentiation into adipocytes and osteocytes was not counteracted by salinomycin, and proliferation capability was not inhibited following salinomycin exposure. The migration of MSC-Sal was attenuated significantly as compared to the MSC-control. There were no genotoxic effects after 4 weeks of salinomycin exposure. The present study shows an altered migration capacity as a sign of functional impairment of MSC induced by chronic salinomycin exposure. Further in vitro toxicological investigations, particularly with primary human cells, are required to understand the impact of chronic salinomycin consumption on human cell systems.

  16. Checking MSC Specifications for Timing Inconsistency

    Institute of Scientific and Technical Information of China (English)

    LI Xuandong(李宣东); TAN Wenkai(谭文凯); ZHENG Guoliang(郑国梁)

    2002-01-01

    Message sequence chart (MSC) is a graphical and textual language for the description and specification of the interactions between system components. MSC specifica tions allow convenient expression of multiple scenarios, and offer an intuitive and visual way of describing design requirements. Like any other aspect of the specification and design process, MSCs are amenable to errors, and their analysis is important. In this paper, the verification problem of MSC specification for timing inconsistency is studied, which means that no execu tion scenario described by an MSC specification is timing consistent. An algorithm is developed to check MSC specifications for timing inconsistency.

  17. GMP-compliant isolation and large-scale expansion of bone marrow-derived MSC.

    Directory of Open Access Journals (Sweden)

    Natalie Fekete

    Full Text Available BACKGROUND: Mesenchymal stromal cells (MSC have gained importance in tissue repair, tissue engineering and in immunosupressive therapy during the last years. Due to the limited availability of MSC in the bone marrow, ex vivo amplification prior to clinical application is requisite to obtain therapeutic applicable cell doses. Translation of preclinical into clinical-grade large-scale MSC expansion necessitates precise definition and standardization of all procedural parameters including cell seeding density, culture medium and cultivation devices. While xenogeneic additives such as fetal calf serum are still widely used for cell culture, its use in the clinical context is associated with many risks, such as prion and viral transmission or adverse immunological reactions against xenogeneic components. METHODS AND FINDINGS: We established animal-free expansion protocols using platelet lysate as medium supplement and thereby could confirm its safety and feasibility for large-scale MSC isolation and expansion. Five different GMP-compliant standardized protocols designed for the safe, reliable, efficient and economical isolation and expansion of MSC was performed and MSC obtained were analyzed for differentiation capacity by qPCR and histochemistry. Expression of standard MSC markers as defined by the International Society for Cellular Therapy as well as expression of additional MSC markers and of various chemokine and cytokine receptors was analysed by flow cytometry. Changes of metabolic markers and cytokines in the medium were addressed using the LUMINEX platform. CONCLUSIONS: The five different systems for isolation and expansion of MSC described in this study are all suitable to produce at least 100 millions of MSC, which is commonly regarded as a single clinical dose. Final products are equal according to the minimal criteria for MSC defined by the ISCT. We showed that chemokine and integrin receptors analyzed had the same expression pattern

  18. Co-cultivation of keratinocyte-human mesenchymal stem cell (hMSC) on sericin loaded electrospun nanofibrous composite scaffold (cationic gelatin/hyaluronan/chondroitin sulfate) stimulates epithelial differentiation in hMSCs: In vitro study.

    Science.gov (United States)

    Bhowmick, Sirsendu; Scharnweber, Dieter; Koul, Veena

    2016-05-01

    Fortifying the scaffold with bioactive molecules and glycosaminoglycans (GAGs), is an efficient way to design new generation tissue engineered biomaterials. In this study, we evaluated the synergistic effect of electrospun nanofibrous composite scaffold (cationic gelatin/hyaluronan/chondroitin sulfate) loaded with sericin and, contact co-culture of human mesenchymal stem cells (hMSCs)-keratinocytes on hMSCs' differentiation towards epithelial lineage. Cationic gelatin is prepared with one step novel synthesis process by grafting quaternary ammonium salts to the backbone of gelatin. Release kinetics studies showed that Fickian diffusion is the major release mechanism for both GAGs and sericin/gelatin. In vitro biocompatibility of the electrospun scaffold was evaluated in terms of LDH and DNA quantification assay on human foreskin fibroblast, human keratinocyte and hMSC. Significant proliferation (∼ 4-6 fold) was detected after culturing all three cell on the electrospun scaffold containing sericin. After 5 days of contact co-culture, results revealed that electrospun scaffold containing sericin promote epithelial differentiation of hMSC in terms of several protein markers (keratin 14, ΔNp63α and Pan-cytokeratin) and gene expression of some dermal proteins (keratin 14, ΔNp63α). Findings of this study will foster the progress of current skin tissue engineering scaffolds by understanding the skin regeneration and wound healing process.

  19. Expansion and Harvesting of hMSC-TERT

    DEFF Research Database (Denmark)

    Weber, Christian; Pohl, Sebastian; Pörtner, Ralf;

    2007-01-01

    cultivation and harvesting. Nonporous microcarriers are preferable when the cells need to be kept in viable condition for further applications like tissue engineering or cell therapy. In this study, the qualification of Biosilon, Cytodex 1, Cytodex 3, RapidCell and P102-L for expansion of h......MSC-TERT with an associated harvesting process using either trypsin, accutase, collagenase or a trypsin-accutase mixture was investigated. A subsequent adipogenic differentiation of harvested hMSC-TERT was performed in order to observe possible negative effects on their (adipogenic) differentiation potential as a result...... of the cultivation and harvesting method. The cultivated cells showed an average growth rate of 0.52 d(-1). The cells cultivated on Biosilon, RapidCell and P102-L were harvested succesfully achieving high cell yield and vitalities near 100%. This was not the case for cells on Cytodex 1 and Cytodex 3. The trypsin...

  20. Human embryonic stem cell-derived mesenchymal stroma cells (hES-MSCs engraft in vivo and support hematopoiesis without suppressing immune function: implications for off-the shelf ES-MSC therapies.

    Directory of Open Access Journals (Sweden)

    Ou Li

    Full Text Available Mesenchymal stroma cells (MSCs have a high potential for novel cell therapy approaches in clinical transplantation. Commonly used bone marrow-derived MSCs (BM-MSCs, however, have a restricted proliferative capacity and cultures are difficult to standardize. Recently developed human embryonic stem cell-derived mesenchymal stroma cells (hES-MSCs might represent an alternative and unlimited source of hMSCs. We therefore compared human ES-cell-derived MSCs (hES-MP002.5 cells to normal human bone marrow-derived MSCs (BM-MSCs. hES-MP002.5 cells had lower yet reasonable CFU-F capacity compared with BM-MSC (8±3 versus 29±13 CFU-F per 100 cells. Both cell types showed similar immunophenotypic properties, i.e. cells were positive for CD105, CD73, CD166, HLA-ABC, CD44, CD146, CD90, and negative for CD45, CD34, CD14, CD31, CD117, CD19, CD 271, SSEA-4 and HLA-DR. hES-MP002.5 cells, like BM-MSCs, could be differentiated into adipocytes, osteoblasts and chondrocytes in vitro. Neither hES-MP002.5 cells nor BM-MSCs homed to the bone marrow of immune-deficient NSG mice following intravenous transplantation, whereas intra-femoral transplantation into NSG mice resulted in engraftment for both cell types. In vitro long-term culture-initiating cell assays and in vivo co-transplantation experiments with cord blood CD34+ hematopoietic cells demonstrated furthermore that hES-MP002.5 cells, like BM-MSCs, possess potent stroma support function. In contrast to BM-MSCs, however, hES-MP002.5 cells showed no or only little activity in mixed lymphocyte cultures and phytohemagglutinin (PHA lymphocyte stimulation assays. In summary, ES-cell derived MSCs might be an attractive unlimited source for stroma transplantation approaches without suppressing immune function.

  1. Different Culture Media Affect Proliferation, Surface Epitope Expression, and Differentiation of Ovine MSC.

    Science.gov (United States)

    Adamzyk, Carina; Emonds, Tanja; Falkenstein, Julia; Tolba, René; Jahnen-Dechent, Wilhelm; Lethaus, Bernd; Neuss, Sabine

    2013-01-01

    Orthopedic implants including engineered bone tissue are commonly tested in sheep. To avoid rejection of heterologous or xenogeneic cells, autologous cells are preferably used, that is, ovine mesenchymal stem cells (oMSC). Unlike human MSC, ovine MSC are not well studied regarding isolation, expansion, and characterization. Here we investigated the impact of culture media composition on growth characteristics, differentiation, and surface antigen expression of oMSC. The culture media varied in fetal calf serum (FCS) content and in the addition of supplements and/or additional epidermal growth factor (EGF). We found that FCS strongly influenced oMSC proliferation and that specific combinations of supplemental factors (MCDB-201, ITS-plus, dexamethasone, and L-ascorbic acid) determined the expression of surface epitopes. We compared two published protocols for oMSC differentiation towards the osteogenic, adipogenic, and chondrogenic fate and found (i) considerable donor to donor variations, (ii) protocol-dependent variations, and (iii) variations resulting from the preculture medium composition. Our results indicate that the isolation and culture of oMSC in different growth media are highly variable regarding oMSC phenotype and behaviour. Furthermore, variations from donor to donor critically influence growth rate, surface marker expression, and differentiation.

  2. Different Culture Media Affect Proliferation, Surface Epitope Expression, and Differentiation of Ovine MSC

    Directory of Open Access Journals (Sweden)

    Carina Adamzyk

    2013-01-01

    Full Text Available Orthopedic implants including engineered bone tissue are commonly tested in sheep. To avoid rejection of heterologous or xenogeneic cells, autologous cells are preferably used, that is, ovine mesenchymal stem cells (oMSC. Unlike human MSC, ovine MSC are not well studied regarding isolation, expansion, and characterization. Here we investigated the impact of culture media composition on growth characteristics, differentiation, and surface antigen expression of oMSC. The culture media varied in fetal calf serum (FCS content and in the addition of supplements and/or additional epidermal growth factor (EGF. We found that FCS strongly influenced oMSC proliferation and that specific combinations of supplemental factors (MCDB-201, ITS-plus, dexamethasone, and L-ascorbic acid determined the expression of surface epitopes. We compared two published protocols for oMSC differentiation towards the osteogenic, adipogenic, and chondrogenic fate and found (i considerable donor to donor variations, (ii protocol-dependent variations, and (iii variations resulting from the preculture medium composition. Our results indicate that the isolation and culture of oMSC in different growth media are highly variable regarding oMSC phenotype and behaviour. Furthermore, variations from donor to donor critically influence growth rate, surface marker expression, and differentiation.

  3. EMT and MET as paradigms for cell fate switching

    Institute of Scientific and Technical Information of China (English)

    Jiekai Chen; Qingkai Han; Duanqing Pei

    2012-01-01

    Cell fate determination is a major unsolved problem in cell and developmental biology,The discovery of reprogramming by pluripotent factors offers a rational system to investigate the molecular mechanisms associated with cell fate decisions.The idea that reprogramming of fibroblasts starts with a mesenchymal-epithelial transition (MET) suggests that the process is perhaps a reversal of epithelial to mesenchymal transition (EMT) found frequently during early embryogenesis,As such,we believe that investigations into MET-EMT may yield detailed molecular insights into cell fate decisions,not only for the switching between epithelial and mesenchymal cells,but also other cell types.

  4. Aging of perennial cells and organ parts according to the programmed aging paradigm.

    Science.gov (United States)

    Libertini, Giacinto; Ferrara, Nicola

    2016-04-01

    If aging is a physiological phenomenon-as maintained by the programmed aging paradigm-it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer's disease, Parkinson's disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.

  5. TOR and paradigm change: cell growth is controlled.

    Science.gov (United States)

    Hall, Michael N

    2016-09-15

    This year marks the 25th anniversary of the discovery of target of rapamycin (TOR), a highly conserved kinase and central controller of cell growth. In this Retrospective, I briefly describe the discovery of TOR and the subsequent elucidation of its cellular role. I place particular emphasis on an article by Barbet et al. from 1996, the first suggesting that TOR controls cell growth in response to nutrients.

  6. New paradigms for metabolic modeling of human cells

    DEFF Research Database (Denmark)

    Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    Abnormalities in cellular functions are associated with the progression of human diseases, often resulting in metabolic reprogramming. GEnome-scale metabolic Models (GEMs) have enabled studying global metabolic reprogramming in connection with disease development in a systematic manner. Here we......, challenges in integration of cell/tissue models for simulation of whole body functions as well as integration of GEMs with other biological networks for generating complete cell/tissue models are presented....... review recent work on reconstruction of GEMs for human cell/tissue types and cancer, and the use of GEMs for identification of metabolic changes occurring in response to disease development. We further discuss how GEMs can be used for the development of efficient therapeutic strategies. Finally...

  7. The nucleolus: a paradigm for cell proliferation and aging.

    Science.gov (United States)

    Comai, L

    1999-12-01

    The nucleolus is the cellular site of ribosome biosynthesis. At this site, active ribosomal DNA (rDNA) genes are rapidly transcribed by RNA polymerase I (pol I) molecules. Recent advances in our understanding of the pol I transcription system have indicated that regulation of ribosomal RNA (rRNA) synthesis is a critical factor in cell growth. Importantly, the same signaling networks that control cell growth and proliferation and are deregulated in cancer appear to control pol I transcription. Therefore, the study of the biochemical basis for growth regulation of pol I transcription can provide basic information about the nuclear signaling network. Hopefully, this information may facilitate the search for drugs that can inhibit the growth of tumor cells by blocking pol I activation. In addition to its function in ribosome biogenesis, recent studies have revealed the prominent role of the nucleolus in cell senescence. These findings have stimulated a new wave of research on the functional relationship between the nucleolus and aging. The aim of this review is to provide an overview of some current topics in the area of nucleolus biology, and it has been written for a general readership.

  8. The nucleolus: a paradigm for cell proliferation and aging

    Directory of Open Access Journals (Sweden)

    Comai L.

    1999-01-01

    Full Text Available The nucleolus is the cellular site of ribosome biosynthesis. At this site, active ribosomal DNA (rDNA genes are rapidly transcribed by RNA polymerase I (pol I molecules. Recent advances in our understanding of the pol I transcription system have indicated that regulation of ribosomal RNA (rRNA synthesis is a critical factor in cell growth. Importantly, the same signaling networks that control cell growth and proliferation and are deregulated in cancer appear to control pol I transcription. Therefore, the study of the biochemical basis for growth regulation of pol I transcription can provide basic information about the nuclear signaling network. Hopefully, this information may facilitate the search for drugs that can inhibit the growth of tumor cells by blocking pol I activation. In addition to its function in ribosome biogenesis, recent studies have revealed the prominent role of the nucleolus in cell senescence. These findings have stimulated a new wave of research on the functional relationship between the nucleolus and aging. The aim of this review is to provide an overview of some current topics in the area of nucleolus biology, and it has been written for a general readership.

  9. Breaking Out of the Cell: On The Benefits of a New Spreadsheet User-Interaction Paradigm

    CERN Document Server

    Hellman, Ziv

    2008-01-01

    Contemporary spreadsheets are plagued by a profusion of errors, auditing difficulties, lack of uniform development methodologies, and barriers to easy comprehension of the underlying business models they represent. This paper presents a case that most of these difficulties stem from the fact that the standard spreadsheet user-interaction paradigm - the 'cell-matrix' approach - is appropriate for spreadsheet data presentation but has significant drawbacks with respect to spreadsheet creation, maintenance and comprehension when workbooks pass a minimal threshold of complexity. An alternative paradigm for the automated generation of spreadsheets directly from plain-language business model descriptions is presented along with its potential benefits. Sunsight Modeller (TM), a working software system implementing the suggested paradigm, is briefly described.

  10. Safety assessment of bone marrow derived MSC grown in platelet-rich plasma

    Directory of Open Access Journals (Sweden)

    Shoji Fukuda

    2015-06-01

    Full Text Available The injection of endothelial progenitor cells and mononuclear cells derived from bone marrow at the ischemic region of peripheral artery disease patients is reported to be effective for therapeutic angiogenesis; however, these cell therapies require large amounts of bone marrow to obtain sufficient numbers of cells. To solve this problem, we attempted to culture bone-marrow-derived mesenchymal stem cells (BM-MSC, which are supposed to secrete several cytokines that promote angiogenesis. We also focused on using platelet-rich plasma (PRP as a supplement for cell culture instead of fetal bovine serum. Human BM-MSC obtained from healthy volunteers expanded rapidly when cultured with 10% PRP prepared from their own blood. FACS analysis revealed that these cultured human MSC were homogeneous populations, and chromosomal analysis showed a normal karyotype. Moreover, the angiogenetic effect was apparent two weeks after human BM-MSC were injected into the ischemic muscle in SCID mice. Tumor formation was not detected three months after injection into SCID mice either subcutaneously or intramuscularly. To simulate clinical settings, canine BM-MSC were grown with canine PRP and injected into their ischemic muscles. We confirmed that donor cells existed in situ two and six weeks after operation without any side effects. These results suggest that cultured human BM-MSC can be a promising cell source for therapeutic angiogenesis.

  11. Niosomes based on synthetic cationic lipids for gene delivery: the influence of polar head-groups on the transfection efficiency in HEK-293, ARPE-19 and MSC-D1 cells.

    Science.gov (United States)

    Ojeda, E; Puras, G; Agirre, M; Zárate, J; Grijalvo, S; Pons, R; Eritja, R; Martinez-Navarrete, G; Soto-Sanchez, C; Fernández, E; Pedraz, J L

    2015-01-28

    We designed niosomes based on three lipids that differed only in the polar-head group to analyze their influence on the transfection efficiency. These lipids were characterized by small-angle X-ray scattering before being incorporated into the niosomes which were characterized in terms of pKa, size, zeta potential, morphology and physical stability. Nioplexes were obtained upon the addition of a plasmid. Different ratios (w/w) were selected to analyze the influence of this parameter on size, charge and the ability to condense, release and protect the DNA. In vitro transfection experiments were performed in HEK-293, ARPE-19 and MSC-D1 cells. Our results show that the chemical composition of the cationic head-group clearly affects the physicochemical parameters of the niosomes and especially the transfection efficiency. Only niosomes based on cationic lipids with a dimethyl amino head group (lipid 3) showed a transfection capacity when compared with their counterparts amino (lipid 1) and tripeptide head-groups (lipid 2). Regarding cell viability, we clearly observed that nioplexes based on the cationic lipid 3 had a more deleterious effect than their counterparts, especially in ARPE-19 cells at 20/1 and 30/1 ratios. Similar studies could be extended to other series of cationic lipids in order to progress in the research on safe and efficient non-viral vectors for gene delivery purposes.

  12. Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction

    DEFF Research Database (Denmark)

    Wright, Elizabeth J; Hodson, Nigel W.; Sherratt, Michael J.

    2016-01-01

    a GLP-1 fusion protein (MSCs ± GLP-1), on human cardiomyocyte apoptosis in vitro. The effect on cardiac remodeling when encapsulated in alginate beads (CellBeads-MSC and CellBeads-MSC + GLP-1) was also evaluated in a pig MI model, whereby pigs were treated with Empty Beads, CellBeads-MSC, or Cell...... were altered following MSC ± GLP treatment. After four weeks, infarcted areas were imaged using atomic force microscopy, demonstrating significant alterations between groups in the structure of collagen fibrils and resulting scar. Conclusions. These data demonstrate that MSCs ± GLP-1 exhibit modulatory...... effects on healing post-MI, affecting both apoptosis and collagen scar formation. These data support the premise that both MSCs and GLP-1 could be beneficial in MI treatment....

  13. Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro

    OpenAIRE

    Scherzad, Agmal; Hackenberg, Stephan; FROELICH, KATRIN; RAK, KRISTEN; Hagen, Rudolf; TAEGER, JOHANNES; BREGENZER, MAXIMILLIAN; KLEINSASSER, NORBERT

    2016-01-01

    Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induc...

  14. Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury.

    Directory of Open Access Journals (Sweden)

    JiangWei Hu

    Full Text Available A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC assay, a hydrogen peroxide (H2O2 content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline that were exposed to 4.5 Gy (60Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-CD117(+: hucMSC-Trx-1 vs. hucMSC, P<0.05; hucMSC-Trx-1 vs. NS, P<0.01, promoting the formation of red blood cells and hemoglobin (hucMSC-Trx-1 vs. hucMSC or NS, P<0.05, reducing inflammation and damage in important organs (Bone marrow and lung: hucMSC-Trx-1 vs. NS, P<0.01; hucMSC-Trx-1 vs. hucMSC, P<0.05. Liver and intestine: hucMSC-Trx-1 vs. NS, P<0.05; hucMSC-Trx-1 vs. hucMSC, P<0.05, and prolonging survival (hucMSC-Trx-1 vs. hucMSC or NS, P<0

  15. The c-Met Inhibitor MSC2156119J Effectively Inhibits Tumor Growth in Liver Cancer Models

    Energy Technology Data Exchange (ETDEWEB)

    Bladt, Friedhelm, E-mail: Friedhelm.Bladt@merckgroup.com; Friese-Hamim, Manja; Ihling, Christian; Wilm, Claudia; Blaukat, Andree [EMD Serono, and Merck Serono Research and Development, Merck KGaA, Darmstadt 64293 (Germany)

    2014-08-19

    The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling.

  16. Marketing: MSc in logistics and transportation

    OpenAIRE

    Jenkins, Mark

    1983-01-01

    The objective of this course is to introduce the basic concepts of marketing to students undertaking an MSc in Transportation and Logistics. This module will take a strategic view of marketing in that it will develop ideas for achieving sustainable competitive advantage.

  17. Sympathetic denervation-induced MSC mobilization in distraction osteogenesis associates with inhibition of MSC migration and osteogenesis by norepinephrine/adrb3.

    Directory of Open Access Journals (Sweden)

    Zhaojie Du

    Full Text Available The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympathetic denervation can deplete norepinephrine (NE in distraction-induced bone callus, down-regulate β3-adrenergic receptor (adrb3 in bone marrow mesenchymal stem cells (MSCs, and promote MSC migration from perivascular regions to bone-forming units. An in vitro Transwell assay was here used to demonstrate that NE can inhibit stroma-derived factor-1 (SDF-1-induced MSC migration and expression of the migration-related gene matrix metalloproteinase-2 (MMP-2 and downregulate that of the anti-migration gene tissue inhibitor of metalloproteinase-3 (TIMP-3. Knockdown of adrb3 using siRNA abolishes inhibition of MSC migration. An in vitro osteogenic assay was used to show that NE can inhibit the formation of MSC bone nodules and expression of the osteogenic marker genes alkaline phosphatase (ALP, osteocalcin (OCN, and runt-related transcription factor-2 (RUNX2, but knockdown of adrb3 by siRNA can abolish such inhibition of the osteogenic differentiation of MSCs. It is here concluded that sympathetic denervation-induced MSC mobilization in rat mandibular distraction osteogenesis is associated with inhibition of MSC migration and osteogenic differentiation by NE/adrb3 in vitro. These findings may facilitate understanding of the relationship of MSC mobilization and sympathetic nervous system across a wide spectrum of tissue regeneration processes.

  18. Pharmacophore-based screening of differentially-expressed PGF, DDIT4, COMP and CHI3L1 from hMSC cell lines reveals five novel therapeutic compounds for primary osteoporosis

    Directory of Open Access Journals (Sweden)

    Catherine Jessica Lai

    2016-06-01

    Full Text Available As many societies age, primary osteoporosis (PO is increasingly a major health problem. Current drug treatments such as alendronate and risedronate have known side effects. We took an agnostic empirical approach to find PO therapeutic compounds. We examined 13,548,960 probe data-points from mesenchymal stromal cell (hMSC lines and found that PGF, DDIT4, and COMP to be up-regulated, and CHI3L1, down-regulated. We then identified their druggable domains. For the up-regulated differentially-expressed genes, we used protein–protein interactions to find residue clusters as binding surfaces. We then employed pharmacophore models to screen 15,407,096 conformations of 22,723,923 compounds, which identified (6R,9R-6-(2-furyl-9-(1H-indol-3-yl-2-(trifluoromethyl-5,6,7, 9-tetrahydro-4H[1,2,4]triazolo[5,1],(2S-N1-[2-[2-(methylamino-2-oxo-ethyl]phenyl]-N2-phenylpyrrolidine-1,2-dicarboxamide, and 2-furyl-(1H-indol-3-yl-methyl-BLAHone as candidate compounds. For the down-regulated CH13L1, we relied on genome-wide disease signatures to identify (11alpha-9-fluoro-11,17,21-trihydroxypregn-4-ene-3,20-dione and Genistein as candidate compounds. Our approach differs from previous research as we did not confine our drug targets to hypothesized compounds in the existing literature. Instead, we allowed the full expression profile of PO cell lines to reveal the most desirable targets. Second, our differential gene analysis revealed both up- and down-regulated genes, in contrast to the literature, which has focused on inhibiting only up-regulated genes. Third, our virtual screening universe of 22,723,923 compounds was more than 100 times larger than those in the known literature.

  19. Teaching a changing paradigm in physiology: a historical perspective on gut interstitial cells.

    Science.gov (United States)

    Drumm, Bernard T; Baker, Salah A

    2017-03-01

    The study and teaching of gastrointestinal (GI) physiology necessitates an understanding of the cellular basis of contractile and electrical coupling behaviors in the muscle layers that comprise the gut wall. Our knowledge of the cellular origin of GI motility has drastically changed over the last 100 yr. While the pacing and coordination of GI contraction was once thought to be solely attributable to smooth muscle cells, it is now widely accepted that the motility patterns observed in the GI tract exist as a result of a multicellular system, consisting of not only smooth muscle cells but also enteric neurons and distinct populations of specialized interstitial cells that all work in concert to ensure proper GI functions. In this historical perspective, we focus on the emerging role of interstitial cells in GI motility and examine the key discoveries and experiments that led to a major shift in a paradigm of GI physiology regarding the role of interstitial cells in modulating GI contractile patterns. A review of these now classic experiments and papers will enable students and educators to fully appreciate the complex, multicellular nature of GI muscles as well as impart lessons on how shifting paradigms in physiology are fueled by new technologies that lead to new emerging discoveries.

  20. Tissue-Resident T Cells as the Central Paradigm of Chlamydia Immunity.

    Science.gov (United States)

    Johnson, Raymond M; Brunham, Robert C

    2016-04-01

    For almost 2 decades, results from Chlamydia pathogenesis investigations have been conceptualized using a cytokine polarization narrative. Recent viral immunity studies identifying protective tissue-resident memory T cells (Trm) suggest an alternative paradigm based on localized immune networks. As Chlamydia vaccines enter the preclinical pipeline and, in the case of an attenuated trachoma vaccine, are given to human subjects, it may be useful to ask whether cytokine polarization is the appropriate framework for understanding and evaluating vaccine efficacy. In this review, we revisit C. trachomatis pathogenesis data from mice and humans using a Trm narrative and note a comfortable concordance with the Chlamydia pathogenesis literature.

  1. Synergistic suppression of autoimmune arthritis through concurrent treatment with tolerogenic DC and MSC

    Science.gov (United States)

    Li, Rong; Zhang, Yujuan; Zheng, Xiufen; Peng, Shanshan; Yuan, Keng; Zhang, Xusheng; Min, Weiping

    2017-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive immune-mediated joint deterioration. Current treatments are not antigen specific and are associated with various adverse. We have previously demonstrated that tolerogenic dendritic cells (Tol-DC) are potent antigen-specific immune regulators, which hold great promise in immunotherapy of autoimmune diseases. In this study, we aimed to develop new immunotherapy by combining Tol-DC and mesenchymal stem cells (MSC). We demonstrated that RelB gene silencing resulted in generation of Tol-DC that suppressed T cell responses and selectively promoted Treg generation. The combination of MSC synergized the tolerogenic capacity of Tol-DC in inhibition of T cell responses. In murine collagen-induced arthritis (CIA) model, we demonstrated that progression of arthritis was inhibited with administration of RelB gene-silenced Tol-DC or MSC. This therapeutic effect was remarkably enhanced with concurrent treatment of combination Tol-DC and MSC as demonstrated by improved clinical symptoms, decreased clinical scores and attenuated joint damage. These therapeutic effects were associated with suppression of CII-specific T cell responses, polarization of Th and inhibition of proinflammatory cytokines, and reduced cartilage degeneration. This study for the first time demonstrates a new approach to treat autoimmune inflammatory joint disease with concurrent treatment of RelB gene-silenced Tol-DC and MSC. PMID:28230210

  2. MSC POOL技术及其发展现状%MSC POOL Technology and Its Development Status

    Institute of Scientific and Technical Information of China (English)

    刘蓉; 李旭

    2011-01-01

    Based on technical research of MSC POOL, the definition and principle of MSC POOL technology are elaborated in a detail. The development status of various manufacturers for MSC POOL technology are summarized. Some typical business examples with MSC POOL technology and the benefits brought by MSC POOL technology in the practical application are analyzed. Finallyt some problems brought by MSC POOL technology and development trend of MSC POOL technology are proposed.%在对MSC POOL技术调研的基础上,详细阐述了MSC POOL技术的定义及原理,然后总结各个厂家针对MSCPOOL技术的发展状况,分析各地的一些典型商用MSC POOL技术实例以及MSC POOL技术在实际应用中所带来的优势,并总结了MSC POOL技术带来的一些问题,展望MSCPOOL技术未来的发展趋势.

  3. [Helper T cell paradigm: Th17 and regulatory T cells involved in autoimmune inflammatory disorders, pathogen defense and allergic diseases].

    Science.gov (United States)

    Noma, Takeshi

    2010-01-01

    The helper T cell paradigm, divided into two distinct subsets, Th1 and Th2 cells, characterized by distinct cytokine and functions, has been expanded to IL-17-producing Th17 cells. Th1 cells producing IFN-γ are involved in delayed-type hypersensitivity, effective in intracellular pathogens defense, while Th2 cells secrete IL-4, IL-5, IL-13 and IL-25 and has a central role in IgE production, eosinophilic inflammation, and the protection for helminthic parasite infection. Th17 cell lineages, expressing IL-17 family of cytokines and IL-23-mediated functions on T cells, plays a role in immune response to fungi and extracellular pathogens and autoimmune inflammatory disorders. Th17 cells are required the combination of IL-6 and TGF-β and the transcription factors, RORC2/RORgt (mice) and STAT3 for differentiation, and produce IL-17, IL-22, IL-17F, IL-21 and CCL20. FOXP3+ regulatory T (Treg) cells produce TGF-β and IL-10, which regulate effector T cells, and thus maintain peripheral tolerance. Four functionally unique CD4+ T cells, including the regulatory T (Treg) cells are now involved in the regulation of immune responses to pathogens, self-antigens and allergens. Any defect in the entire CD4+T cell population might results in human diseases. In this review, the biology of Th17 cells and Treg cells and their role in immune diseases are presented.

  4. Engineering biomaterial surfaces using nanoparticle assemblies: A new paradigm for modulating cell function

    Science.gov (United States)

    Lipski, Anna Marie

    Silica nanoparticles (NP) were investigated as a surface modification medium and their impact on cell function was studied. This work has demonstrated that NP assemblies are suitable for the surface modification of both metal and polymer substrates. Additionally, important surface parameters, such as nano-roughness, charge, and chemistry, can be imparted in a predictable manner. More importantly, by varying the NP size, nano-roughness of a surface can be varied independent of chemistry. Two terminally differentiated mammalian cell types, bovine aortic endothelial cells (BAEC) and murine calvarial osteoblast-like cells (MC3T3-E1), were used to probe the effects of nano-topography on cell proliferation, metabolic activity, spreading, cytoskeletal F-actin alignment, and focal adhesion recruitment. Furthermore, the influence of nano-topography on cell migration was studied using BAEC and human fetal osteoblasts (hFOB). The results suggested that surface nano-rugosity affects cell behavior at various levels and that these effects are cell type specific; however, some clear trends were discerned with respect to F-actin alignment and cell migration. In particular, presentation of nano-features resulted in enhancement of cytoskeletal F-actin alignment along the long axis of the cells in comparison to unmodified glass. With respect to cell migration, increased nano-roughness resulted in decreased migration rates for both BAEC and hFOB. Finally, the potential of nano-rugosity as a mediator of cell differentiation was investigated by following the lineage specific differentiation of human marrow-derived mesenchymal progenitor cells (MPC) on NP-modified 316L stainless steel and titanium substrates. It was observed that NP modification enhanced the differentiation of MPC into an osteogenic lineage and that rugosity appeared to be the dominant factor in directing this differentiation. Thus, coatings composed of silica NPs presented a new paradigm that may lend themselves to

  5. Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation.

    Science.gov (United States)

    Ropper, Alexander E; Thakor, Devang K; Han, InBo; Yu, Dou; Zeng, Xiang; Anderson, Jamie E; Aljuboori, Zaid; Kim, Soo-Woo; Wang, Hongjun; Sidman, Richard L; Zafonte, Ross D; Teng, Yang D

    2017-01-31

    Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system. Also, in rat T9-T10 hemisection spinal cord injury (SCI), we demonstrated that the tailored scaffolding maintained hMSC stemness, engraftment, and led to robust motosensory improvement, neuropathic pain and tissue damage mitigation, and myelin preservation. The scaffolded nontransdifferentiated hMSCs exerted multimodal effects of neurotrophism, angiogenesis, neurogenesis, antiautoimmunity, and antiinflammation. Hindlimb locomotion was restored by reestablished integrity of submidbrain circuits of serotonergic reticulospinal innervation at lumbar levels, the propriospinal projection network, neuromuscular junction, and central pattern generator, providing a platform for investigating molecular events underlying the repair impact of nondifferentiated hMSCs. Our approach enabled investigation of recovery neurobiology components for injured adult mammalian spinal cord that are different from those involved in normal neural function. The uncovered neural circuits and their molecular and cellular targets offer a biological underpinning for development of clinical rehabilitation therapies to treat disabilities and complications of SCI.

  6. MSC POOL网络组网方案研究

    Institute of Scientific and Technical Information of China (English)

    孙志刚; 姜金池

    2015-01-01

    MSC POOL是在3G R5版本中引入软交换核心网的一项重要技术。通过将某一区域的交换机组建成MSC POOL网络,极大地提高了通信网络的安全性。本文通过对MSC POOL技术进行深入研究,提出了一种以MGW媒体网关做NNSF代理的MSC POOL组网方式,并对可行性进行了论证。

  7. The evolving paradigm of cell-nonautonomous UPR-based regulation of immunity by cancer cells.

    Science.gov (United States)

    Zanetti, M; Rodvold, J J; Mahadevan, N R

    2016-01-21

    The endoplasmic reticulum (ER) stress response/unfolded protein response (UPR) has been thought to influence tumorigenesis mainly through cell-intrinsic, pro-survival effects. In recent years, however, new evidence has emerged showing that the UPR is also the source of cell-extrinsic effects, particularly directed at those immune cells within the tumor microenvironment. Here we will review and discuss this new body of information with focus on the role of cell-extrinsic effects on innate and adaptive immunity, suggesting that the transmission of ER stress from cancer cells to myeloid cells in particular is an expedient used by cancer cells to control the immune microenvironment, which acquires pro-inflammatory as well as immune-suppressive characteristics. These new findings can now be seen in the broader context of similar phenomena described in Caenorhabditis elegans, and an analogy with quorum sensing and 'community effects' in prokaryotes and eukaryotes can be drawn, arguing that a cell-nonautonomous UPR-based regulation of heterologous cells may be phylogenetically conserved. Finally, we will discuss the role of aneuploidy as an inducer of proteotoxic stress and potential initiator of cell-nonautonomous UPR-based regulation. In presenting these new views, we wish to bring attention to the cell-extrinsic regulation of tumor growth, including tumor UPR-based cell-nonautonomous signaling as a mechanism of maintaining tumor heterogeneity and resistance to therapy, and suggest therapeutically targeting such mechanisms within the tumor microenvironment.

  8. Transitional B cells in early human B cell development - time to revisit the paradigm?

    Directory of Open Access Journals (Sweden)

    Victoria G Martin

    2016-12-01

    Full Text Available The B cell repertoire is generated in the adult bone marrow by an ordered series of gene rearrangement processes that result in massive diversity of immunoglobulin (Ig genes, and consequently an equally large number of potential specificities for antigen. As the process is essentially random, then cells exhibiting excess reactivity with self-antigens are generated and need to be removed from the repertoire before the cells are fully mature. Some of the cells are deleted, and some will undergo receptor editing to see if changing the light chain can rescue an autoreactive antibody. As a consequence, the binding properties of the B cell receptor are changed as development progresses through pre-B>>immature>>transitional>>naïve phenotypes. Using long-read, high-throughput, sequencing we have produced a unique set of sequences from these four cell types in human bone marrow and matched peripheral blood and our results describe the effects of tolerance selection on the B cell repertoire at the Ig gene level. Most strong effects of selection are seen within the heavy chain repertoire, and can be seen both in gene usage and in CDR-H3 characteristics. Age-related changes are small and only the size of the CDR-H3 shows constant and significant change in these data. The paucity of significant changes in either kappa or lambda light chain repertoires implies that either the heavy chain has more influence over autoreactivity than light chain and/or that switching between kappa and lambda light chains, as opposed to switching within the light chain loci, may effect a more successful autoreactive rescue by receptor editing. Our results show that the transitional cell population contains cells other than those that are part of the pre-B>>immature>>transitional>>naïve development pathway, since the population often shows a repertoire that is outside the trajectory of gene loss/gain between pre-B and naïve stages.

  9. In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

    Directory of Open Access Journals (Sweden)

    Ribot EJ

    2014-04-01

    Full Text Available Emeline J Ribot,1 Jeffrey M Gaudet,1,2 Yuhua Chen,1 Kyle M Gilbert,1 Paula J Foster1,2 1Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada; 2Department of Medical Biophysics, University of Western Ontario, London, ON, Canada Abstract: Mesenchymal stem cells (MSC are used to restore deteriorated cell environments. There is a need to specifically track these cells following transplantation in order to evaluate different methods of implantation, to follow their migration within the body, and to quantify their accumulation at the target. Cellular magnetic resonance imaging (MRI using fluorine-based nanoemulsions is a great means to detect these transplanted cells in vivo because of the high specificity for fluorine detection and the capability for precise quantification. This technique, however, has low sensitivity, necessitating improvement in MR sequences. To counteract this issue, the balanced steady-state free precession (bSSFP imaging sequence can be of great interest due to the high signal-to-noise ratio (SNR. Furthermore, it can be applied to obtain 3D images within short acquisition times. In this paper, bSSFP provided accurate quantification of samples of the perfluorocarbon Cell Sense-labeled cells in vitro. Cell Sense was internalized by human MSC (hMSC without adverse alterations in cell viability or differentiation into adipocytes/osteocytes. The bSSFP sequence was applied in vivo to track and quantify the signals from both Cell Sense-labeled and iron-labeled hMSC after intramuscular implantation. The fluorine signal was observed to decrease faster and more significantly than the volume of iron-associated voids, which points to the advantage of quantifying the fluorine signal and the complexity of quantifying signal loss due to iron. Keywords: bSSFP, fluorine MRI, mesenchymal stem cell, mouse, cell tracking

  10. Mineralized collagen scaffolds induce hMSC osteogenesis and matrix remodeling.

    Science.gov (United States)

    Weisgerber, Daniel W; Caliari, Steven R; Harley, Brendan A C

    2015-03-01

    Biomaterials for bone tissue engineering must be able to instruct cell behavior in the presence of the complex biophysical and biomolecular environments encountered in vivo. While soluble supplementation strategies have been identified to enhance osteogenesis, they are subject to significant diffusive loss in vivo or the need for frequent re-addition in vitro. This investigation therefore explored whether biophysical and biochemical properties of a mineralized collagen-GAG scaffold were sufficient to enhance human mesenchymal stem cell (hMSC) osteogenic differentiation and matrix remodeling in the absence of supplementation. We examined hMSC metabolic health, osteogenic and matrix gene expression profiles, as well as matrix remodeling and mineral formation as a function of scaffold mineral content. We found that scaffold mineral content enhanced long term hMSC metabolic activity relative to non-mineralized scaffolds. While osteogenic supplementation or exogenous BMP-2 could enhance some markers of hMSC osteogenesis in the mineralized scaffold, we found the mineralized scaffold was itself sufficient to induce osteogenic gene expression, matrix remodeling, and mineral formation. Given significant potential for unintended consequences with the use of mixed media formulations and potential for diffusive loss in vivo, these findings will inform the design of instructive biomaterials for regenerative repair of critical-sized bone defects, as well as for applications where non-uniform responses are required, such as in biomaterials to address spatially-graded interfaces between orthopedic tissues.

  11. Transitional B Cells in Early Human B Cell Development – Time to Revisit the Paradigm?

    Science.gov (United States)

    Martin, Victoria G.; Wu, Yu-Chang Bryan; Townsend, Catherine L.; Lu, Grace H. C.; O’Hare, Joselli Silva; Mozeika, Alexander; Coolen, Anthonius C. C.; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K.

    2016-01-01

    The B cell repertoire is generated in the adult bone marrow by an ordered series of gene rearrangement processes that result in massive diversity of immunoglobulin (Ig) genes and consequently an equally large number of potential specificities for antigen. As the process is essentially random, the cells exhibiting excess reactivity with self-antigens are generated and need to be removed from the repertoire before the cells are fully mature. Some of the cells are deleted, and some will undergo receptor editing to see if changing the light chain can rescue an autoreactive antibody. As a consequence, the binding properties of the B cell receptor are changed as development progresses through pre-B ≫ immature ≫ transitional ≫ naïve phenotypes. Using long-read, high-throughput, sequencing we have produced a unique set of sequences from these four cell types in human bone marrow and matched peripheral blood, and our results describe the effects of tolerance selection on the B cell repertoire at the Ig gene level. Most strong effects of selection are seen within the heavy chain repertoire and can be seen both in gene usage and in CDRH3 characteristics. Age-related changes are small, and only the size of the CDRH3 shows constant and significant change in these data. The paucity of significant changes in either kappa or lambda light chain repertoires implies that either the heavy chain has more influence over autoreactivity than light chain and/or that switching between kappa and lambda light chains, as opposed to switching within the light chain loci, may effect a more successful autoreactive rescue by receptor editing. Our results show that the transitional cell population contains cells other than those that are part of the pre-B ≫ immature ≫ transitional ≫ naïve development pathway, since the population often shows a repertoire that is outside the trajectory of gene loss/gain between pre-B and naïve stages. PMID:27994589

  12. Optimization and translation of MSC-based hyaluronic acid hydrogels for cartilage repair

    Science.gov (United States)

    Erickson, Isaac E.

    2011-12-01

    Traumatic injury and disease disrupt the ability of cartilage to carry joint stresses and, without an innate regenerative response, often lead to degenerative changes towards the premature development of osteoarthritis. Surgical interventions have yet to restore long-term mechanical function. Towards this end, tissue engineering has been explored for the de novo formation of engineered cartilage as a biologic approach to cartilage repair. Research utilizing autologous chondrocytes has been promising, but clinical limitations in their yield have motivated research into the potential of mesenchymal stem cells (MSCs) as an alternative cell source. MSCs are multipotent cells that can differentiate towards a chondrocyte phenotype in a number of biomaterials, but no combination has successfully recapitulated the native mechanical function of healthy articular cartilage. The broad objective of this thesis was to establish an MSC-based tissue engineering approach worthy of clinical translation. Hydrogels are a common class of biomaterial used for cartilage tissue engineering and our initial work demonstrated the potential of a photo-polymerizable hyaluronic acid (HA) hydrogel to promote MSC chondrogenesis and improved construct maturation by optimizing macromer and MSC seeding density. The beneficial effects of dynamic compressive loading, high MSC density, and continuous mixing (orbital shaker) resulted in equilibrium modulus values over 1 MPa, well in range of native tissue. While compressive properties are crucial, clinical translation also demands that constructs stably integrate within a defect. We utilized a push-out testing modality to assess the in vitro integration of HA constructs within artificial cartilage defects. We established the necessity for in vitro pre-maturation of constructs before repair to achieve greater integration strength and compressive properties in situ. Combining high MSC density and gentle mixing resulted in integration strength over 500 k

  13. Therapeutic MSC exosomes are derived from lipid raft microdomains in the plasma membrane

    Directory of Open Access Journals (Sweden)

    Soon Sim Tan

    2013-12-01

    Full Text Available Background: Mesenchymal stem cell (MSC was previously shown to secrete lipid vesicles that when purified by high performance liquid chromatography as a population of homogenously sized particles with a hydrodynamic radius of 55–65 nm reduce infarct size in a mouse model of myocardial ischemia/reperfusion injury. As these vesicles exhibit many biophysical and biochemical properties of exosomes, they were identified as exosomes. Here we investigated if these lipid vesicles were indeed exosomes that have an endosomal biogenesis. Method: In most cells, endocytosis is thought to occur at specialized microdomains known as lipid rafts. To demonstrate an endosomal origin for MSC exosomes, MSCs were pulsed with ligands e.g. transferrin (Tfs and Cholera Toxin B (CTB that bind receptors in lipid rafts. The endocytosed ligands were then chased to determine if they were incorporated into the exosomes. Results: A fraction of exogenous Tfs was found to recycle into MSC exosomes. When MSCs were pulsed with labelled Tfs in the presence of chlorpromazine, an inhibitor of clathrin-mediated endocytosis, Tf incorporation in CD81-immunoprecipitate was reduced during the chase. CTB which binds GM1 gangliosides that are enriched in lipid rafts extracted exosome-associated proteins, CD81, CD9, Alix and Tsg101 from MSC-conditioned medium. Exogenous CTBs were pulse-chased into secreted vesicles. Extraction of Tf- or CTB-binding vesicles in an exosome preparation mutually depleted each other. Inhibition of sphingomyelinases reduced CTB-binding vesicles. Conclusion: Together, our data demonstrated that MSC exosomes are derived from endocytosed lipid rafts and that their protein cargo includes exosome-associated proteins CD81, CD9, Alix and Tsg101.

  14. Mechanical strain downregulates C/EBPβ in MSC and decreases endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Maya Styner

    Full Text Available Exercise prevents marrow mesenchymal stem cell (MSC adipogenesis, reversing trends that accompany aging and osteoporosis. Mechanical input, the in-vitro analogue to exercise, limits PPARγ expression and adipogenesis in MSC. We considered whether C/EBPβ might be mechanoresponsive as it is upstream to PPARγ, and also is known to upregulate endoplasmic reticulum (ER stress. MSC (C3H10T1/2 pluripotent cells as well as mouse marrow-derived MSC were cultured in adipogenic media and a daily mechanical strain regimen was applied. We demonstrate herein that mechanical strain represses C/EBPβ mRNA (0.6-fold ±0.07, p<0.05 and protein (0.4-fold ±0.1, p<0.01 in MSC. SiRNA silencing of β-catenin prevented mechanical repression of C/EBPβ. C/EBPβ overexpression did not override strain's inhibition of adipogenesis, which suggests that mechanical control of C/EBPβ is not the primary site at which adipogenesis is regulated. Mechanical inhibition of C/EBPβ, however, might be critical for further processes that regulate MSC health. Indeed, overexpression of C/EBPβ in MSC induced ER stress evidenced by a dose-dependent increase in the pro-apoptotic CHOP (protein 4-fold ±0.5, p<0.05 and a threshold reduction in the chaperone BiP (protein 0.6-fold ±0.1, p = 0.2; mRNA 0.3-fold ±0.1, p<0.01. ChIP-seq demonstrated a significant association between C/EBPβ and both CHOP and BiP genes. The strain regimen, in addition to decreasing C/EBPβ mRNA (0.5-fold ±0.09, p<0.05, expanded ER capacity as measured by an increase in BiP mRNA (2-fold ±0.2, p<0.05 and protein. Finally, ER stress induced by tunicamycin was ameliorated by mechanical strain as demonstrated by decreased C/EBPβ, increased BiP and decreased CHOP protein expression. Thus, C/EBPβ is a mechanically responsive transcription factor and its repression should counter increases in marrow fat as well as improve skeletal resistance to ER stress.

  15. MSc Thesis: Presentation of Certain New Trends in Noncommutative Geometry

    CERN Document Server

    Buachalla, Réamonn Ó

    2011-01-01

    MSc thesis of the author offering an introduction to the operator algebraic approach to noncommutative geometry, with a treatment of some more advanced elements such as the noncommutative geometry of quantum groups, fuzzy physics, and compact quantum metric spaces.

  16. An MSc Course Module: Wind Turbine Measurement Techniques

    DEFF Research Database (Denmark)

    Hansen, Kurt Schaldemose; Pedersen, Knud Ole Helgesen

    2005-01-01

    The 2-year MSc in Wind power engineering at the Technical University of Denmark comprises modules from core engineering teaching and from other modules specifically designed to the MSc. This Note outlines the content of such a specific module on the subject of wind turbine measurement. The lectures......, practical exercises and work related to measurements from an operating 500 kW turbine are described....

  17. NNSF Deployment within MSC Pool Technology%MSC Pool技术中NNSF的部署方式

    Institute of Scientific and Technical Information of China (English)

    龙滔滔

    2008-01-01

    本文首先介绍了MSC Pool的技术原理与组网优势,然后对MSC Pool技术中NNSF的两种部署方式做了重点阐述,说明了由MGW代理实现NNSF的信令组网方式,并且介绍了一种比较可行的组网实现方案.

  18. A Paradigm Shift on the Question of B Cells in Transplantation? Recent Insights on Regulating the Alloresponse.

    Science.gov (United States)

    Firl, Daniel J; Benichou, Gilles; Kim, James I; Yeh, Heidi

    2017-01-01

    B lymphocytes contribute to acute and chronic allograft rejection through their production of donor-specific antibodies (DSAs). In addition, B cells present allopeptides bound to self-MHC class II molecules and provide costimulation signals to T cells, which are essential to their activation and differentiation into memory T cells. On the other hand, both in laboratory rodents and patients, the concept of effector T cell regulation by B cells is gaining traction in the field of transplantation. Specifically, clinical trials using anti-CD20 monoclonal antibodies to deplete B cells and reverse DSA had a deleterious effect on rates of acute cellular rejection; a peculiar finding that calls into question a central paradigm in transplantation. Additional work in humans has characterized IL-10-producing B cells (IgM memory and transitional B cells), which suppress the proliferation and inflammatory cytokine productions of effector T cells in vitro. Understanding the mechanisms of regulating the alloresponse is critical if we are to achieve operational tolerance across transplantation. This review will focus on recent evidence in murine and human transplantation with respect to non-traditional roles for B cells in determining clinical outcomes.

  19. YidC is required for the assembly of the MscL homopentameric pore

    NARCIS (Netherlands)

    Pop, Ovidiu I.; Soprova, Zora; Koningstein, Gregory; Scheffers, Dirk-Jan; Ulsen, Peter van; Wickström, David; Gier, Jan-Willem de; Luirink, Joen

    2009-01-01

    The mechanosensitive channel with large conductance (MscL) of Escherichia coli is formed by a homopentameric assembly of MscL proteins. Here, we describe MscL biogenesis as determined using in vivo approaches. Evidence is presented that MscL is targeted to the inner membrane via the signal recogniti

  20. An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome

    Science.gov (United States)

    Wu, Yi-Hsuan; Taggart, Janet; Song, Pamela Xiyao; MacDiarmid, Colin; Eide, David J.

    2016-01-01

    The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5’ end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5’ UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5’ UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5’ UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID:27657924

  1. Reversibility of cellular aging by reprogramming through an embryonic-like state : a new paradigm for human cell rejuvenation

    Directory of Open Access Journals (Sweden)

    Jean-Marc Lemaitre

    2014-01-01

    Full Text Available Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs provides a unique opportunity to derive patient-specific stem cells with potential application in autologous tissue replacement therapies and without the ethical concerns of Embryonic Stem Cells (hESC. However, this strategy still suffers from several hurdles that need to be overcome before clinical applications. Among them, cellular senescence, which contributes to aging and restricted longevity, has been described as a barrier to the derivation of iPSCs. This suggests that aging might be an important limitation for therapeutic purposes for elderly individuals. Senescence is characterized by an irreversible cell cycle arrest in response to various forms of stress, including activation of oncogenes, shortened telomeres, DNA damage, oxidative stress, and mitochondrial dysfunction. To overcome this barrier, we developed an optimized 6-factor-based reprogramming protocol that is able to cause efficient reversing of cellular senescence and reprogramming into iPSCs. We demonstrated that iPSCs derived from senescent and centenarian fibroblasts have reset telomere size, gene expression profiles, oxidative stress, and mitochondrial metabolism, and are indistinguishable from hESC. Finally, we demonstrate that re-differentiation led to rejuvenated cells with a reset cellular physiology, defining a new paradigm for human cell rejuvenation. We discuss the molecular mechanisms involved in cell reprogramming of senescent cells

  2. Rationale and design of the first randomized, double-blind, placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal Stromal Cells in chronic ischemic Heart Failure (MSC-HF Trial)

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Jørgensen, Erik; Qayyum, Abbas Ali;

    2012-01-01

    Stem cell therapy is an emerging treatment modality in cardiovascular disease. The best cell type and delivery method in different cardiovascular diseases remain to be determined.......Stem cell therapy is an emerging treatment modality in cardiovascular disease. The best cell type and delivery method in different cardiovascular diseases remain to be determined....

  3. THE EFFECTS OF CULTURE ON KNOWLEDGE MANAGEMENT PRACTICE: A QUALITATIVE CASE STUDY OF MSC STATUS COMPANIES

    Directory of Open Access Journals (Sweden)

    Charmaine Ryan

    2006-01-01

    Full Text Available Knowledge is recognised as being an important asset in organisations these days. Despite this, many organisations are not doing enough to effectively manage this important asset for its competitive advantage. In response to this, knowledge management which is defined as a process that effectively creates, captures, shares and uses organisation-wide knowledge to improve the organisation’s performance was conceived and has since gained widespread acceptance the world over. Despite its widespread acceptance, little is known about the current levels of knowledge management within the Malaysian context, in particular amongst the Multimedia Super Corridor (MSC status companies in Malaysia. Furthermore, the extent to which cultural factors impact upon knowledge management practice in these companies is not known. This study investigated the various cultural factors (collaboration, mutual trust, leadership and incentives/rewards using a multiple case study approach operating within a critical realism research paradigm and found that these factors have impact on the level of knowledge management practice. The study also established that cultural factors do play an important role in facilitating knowledge management practice in these MSC status companies in Malaysia. It was found that collaboration, mutual trust, leadership, kiasu-ism and incentives/rewards have significant impact on the level of knowledge management practice. In view of the findings of this study, it is suggested that the relevant authorities pay adequate attention on these cultural factors to ensure that the knowledge management initiatives undertaken by Malaysian companies are effectively deployed.

  4. Osteogenic Differentiation of MSC through Calcium Signaling Activation: Transcriptomics and Functional Analysis.

    Science.gov (United States)

    Viti, Federica; Landini, Martina; Mezzelani, Alessandra; Petecchia, Loredana; Milanesi, Luciano; Scaglione, Silvia

    2016-01-01

    The culture of progenitor mesenchymal stem cells (MSC) onto osteoconductive materials to induce a proper osteogenic differentiation and mineralized matrix regeneration represents a promising and widely diffused experimental approach for tissue-engineering (TE) applications in orthopaedics. Among modern biomaterials, calcium phosphates represent the best bone substitutes, due to their chemical features emulating the mineral phase of bone tissue. Although many studies on stem cells differentiation mechanisms have been performed involving calcium-based scaffolds, results often focus on highlighting production of in vitro bone matrix markers and in vivo tissue ingrowth, while information related to the biomolecular mechanisms involved in the early cellular calcium-mediated differentiation is not well elucidated yet. Genetic programs for osteogenesis have been just partially deciphered, and the description of the different molecules and pathways operative in these differentiations is far from complete, as well as the activity of calcium in this process. The present work aims to shed light on the involvement of extracellular calcium in MSC differentiation: a better understanding of the early stage osteogenic differentiation program of MSC seeded on calcium-based biomaterials is required in order to develop optimal strategies to promote osteogenesis through the use of new generation osteoconductive scaffolds. A wide spectrum of analysis has been performed on time-dependent series: gene expression profiles are obtained from samples (MSC seeded on calcium-based scaffolds), together with related microRNAs expression and in vivo functional validation. On this basis, and relying on literature knowledge, hypotheses are made on the biomolecular players activated by the biomaterial calcium-phosphate component. Interestingly, a key role of miR-138 was highlighted, whose inhibition markedly increases osteogenic differentiation in vitro and enhance ectopic bone formation in vivo

  5. Osteogenic Differentiation of MSC through Calcium Signaling Activation: Transcriptomics and Functional Analysis.

    Directory of Open Access Journals (Sweden)

    Federica Viti

    Full Text Available The culture of progenitor mesenchymal stem cells (MSC onto osteoconductive materials to induce a proper osteogenic differentiation and mineralized matrix regeneration represents a promising and widely diffused experimental approach for tissue-engineering (TE applications in orthopaedics. Among modern biomaterials, calcium phosphates represent the best bone substitutes, due to their chemical features emulating the mineral phase of bone tissue. Although many studies on stem cells differentiation mechanisms have been performed involving calcium-based scaffolds, results often focus on highlighting production of in vitro bone matrix markers and in vivo tissue ingrowth, while information related to the biomolecular mechanisms involved in the early cellular calcium-mediated differentiation is not well elucidated yet. Genetic programs for osteogenesis have been just partially deciphered, and the description of the different molecules and pathways operative in these differentiations is far from complete, as well as the activity of calcium in this process. The present work aims to shed light on the involvement of extracellular calcium in MSC differentiation: a better understanding of the early stage osteogenic differentiation program of MSC seeded on calcium-based biomaterials is required in order to develop optimal strategies to promote osteogenesis through the use of new generation osteoconductive scaffolds. A wide spectrum of analysis has been performed on time-dependent series: gene expression profiles are obtained from samples (MSC seeded on calcium-based scaffolds, together with related microRNAs expression and in vivo functional validation. On this basis, and relying on literature knowledge, hypotheses are made on the biomolecular players activated by the biomaterial calcium-phosphate component. Interestingly, a key role of miR-138 was highlighted, whose inhibition markedly increases osteogenic differentiation in vitro and enhance ectopic bone

  6. MSC POOL工程实施方案研究

    Institute of Scientific and Technical Information of China (English)

    龙滔滔

    2012-01-01

    文章首先介绍MSC POOL技术的原理及优点,然后详细分析了在新建或改造MSC POOL过程中需要注意的问题,包括:池区规划的原则、需要规划的数据、四种POOL内组网方案的比较以及信令组网方式的选择,并总结了NRI与TMSI及系统容量的关系,为整个MSC POOL网络的工程实施提供了经验依据.

  7. MSC Pool组网规划研究及问题分析

    Institute of Scientific and Technical Information of China (English)

    黄嘉

    2007-01-01

    简要介绍了MSC Pool的技术原理,对目前MSC Pool技术应用存在的问题进行了分析,并针对引入MSC Pool带来的影响进行了探讨,重点讨论了 MSC Pool组网的要点和原则.并给出了MSC Pool组网规划的相关建议.

  8. The Effect of Detergent, Temperature, and Lipid on the Oligomeric State of MscL Constructs: Insights from Mass Spectrometry.

    Science.gov (United States)

    Reading, Eamonn; Walton, Troy A; Liko, Idlir; Marty, Michael T; Laganowsky, Arthur; Rees, Douglas C; Robinson, Carol V

    2015-05-21

    The mechanosensitive channel of large conductance (MscL) acts as an emergency release valve for osmotic shock of bacteria preventing cell lysis. The large pore size, essential for function, requires the formation of oligomers with tetramers, pentamers, or hexamers observed depending on the species and experimental approach. We applied non-denaturing (native) mass spectrometry to five different homologs of MscL to determine the oligomeric state under more than 50 different experimental conditions elucidating lipid binding and subunit stoichiometry. We found equilibrium between pentameric and tetrameric species, which can be altered by detergent, disrupted by binding specific lipids, and perturbed by increasing temperature (37°C). We also established the presence of lipopolysaccharide bound to MscL and other membrane proteins expressed in Escherichia coli, revealing a potential source of heterogeneity. More generally, we highlight the use of mass spectrometry in probing membrane proteins under a variety of detergent-lipid environments relevant to structural biology.

  9. Mutations in a Conserved Domain of E. coli MscS to the Most Conserved Superfamily Residue Leads to Kinetic Changes.

    Directory of Open Access Journals (Sweden)

    Hannah R Malcolm

    Full Text Available In Escherichia coli (E. coli the mechanosensitive channel of small conductance, MscS, gates in response to membrane tension created from acute external hypoosmotic shock, thus rescuing the bacterium from cell lysis. E. coli MscS is the most well studied member of the MscS superfamily of channels, whose members are found throughout the bacterial and plant kingdoms. Homology to the pore lining helix and upper vestibule domain of E. coli MscS is required for inclusion into the superfamily. Although highly conserved, in the second half of the pore lining helix (TM3B, E. coli MscS has five residues significantly different from other members of the superfamily. In superfamilies such as this, it remains unclear why variations within such a homologous region occur: is it tolerance of alternate residues, or does it define functional variance within the superfamily? Point mutations (S114I/T, L118F, A120S, L123F, F127E/K/T and patch clamp electrophysiology were used to study the effect of changing these residues in E. coli MscS on sensitivity and gating. The data indicate that variation at these locations do not consistently lead to wildtype channel phenotypes, nor do they define large changes in mechanosensation, but often appear to effect changes in the E. coli MscS channel gating kinetics.

  10. Mutations in a Conserved Domain of E. coli MscS to the Most Conserved Superfamily Residue Leads to Kinetic Changes.

    Science.gov (United States)

    Malcolm, Hannah R; Blount, Paul

    2015-01-01

    In Escherichia coli (E. coli) the mechanosensitive channel of small conductance, MscS, gates in response to membrane tension created from acute external hypoosmotic shock, thus rescuing the bacterium from cell lysis. E. coli MscS is the most well studied member of the MscS superfamily of channels, whose members are found throughout the bacterial and plant kingdoms. Homology to the pore lining helix and upper vestibule domain of E. coli MscS is required for inclusion into the superfamily. Although highly conserved, in the second half of the pore lining helix (TM3B), E. coli MscS has five residues significantly different from other members of the superfamily. In superfamilies such as this, it remains unclear why variations within such a homologous region occur: is it tolerance of alternate residues, or does it define functional variance within the superfamily? Point mutations (S114I/T, L118F, A120S, L123F, F127E/K/T) and patch clamp electrophysiology were used to study the effect of changing these residues in E. coli MscS on sensitivity and gating. The data indicate that variation at these locations do not consistently lead to wildtype channel phenotypes, nor do they define large changes in mechanosensation, but often appear to effect changes in the E. coli MscS channel gating kinetics.

  11. Adaptive control paradigm for photovoltaic and solid oxide fuel cell in a grid-integrated hybrid renewable energy system

    Science.gov (United States)

    Khan, Laiq

    2017-01-01

    The hybrid power system (HPS) is an emerging power generation scheme due to the plentiful availability of renewable energy sources. Renewable energy sources are characterized as highly intermittent in nature due to meteorological conditions, while the domestic load also behaves in a quite uncertain manner. In this scenario, to maintain the balance between generation and load, the development of an intelligent and adaptive control algorithm has preoccupied power engineers and researchers. This paper proposes a Hermite wavelet embedded NeuroFuzzy indirect adaptive MPPT (maximum power point tracking) control of photovoltaic (PV) systems to extract maximum power and a Hermite wavelet incorporated NeuroFuzzy indirect adaptive control of Solid Oxide Fuel Cells (SOFC) to obtain a swift response in a grid-connected hybrid power system. A comprehensive simulation testbed for a grid-connected hybrid power system (wind turbine, PV cells, SOFC, electrolyzer, battery storage system, supercapacitor (SC), micro-turbine (MT) and domestic load) is developed in Matlab/Simulink. The robustness and superiority of the proposed indirect adaptive control paradigm are evaluated through simulation results in a grid-connected hybrid power system testbed by comparison with a conventional PI (proportional and integral) control system. The simulation results verify the effectiveness of the proposed control paradigm. PMID:28329015

  12. Adaptive control paradigm for photovoltaic and solid oxide fuel cell in a grid-integrated hybrid renewable energy system.

    Science.gov (United States)

    Mumtaz, Sidra; Khan, Laiq

    2017-01-01

    The hybrid power system (HPS) is an emerging power generation scheme due to the plentiful availability of renewable energy sources. Renewable energy sources are characterized as highly intermittent in nature due to meteorological conditions, while the domestic load also behaves in a quite uncertain manner. In this scenario, to maintain the balance between generation and load, the development of an intelligent and adaptive control algorithm has preoccupied power engineers and researchers. This paper proposes a Hermite wavelet embedded NeuroFuzzy indirect adaptive MPPT (maximum power point tracking) control of photovoltaic (PV) systems to extract maximum power and a Hermite wavelet incorporated NeuroFuzzy indirect adaptive control of Solid Oxide Fuel Cells (SOFC) to obtain a swift response in a grid-connected hybrid power system. A comprehensive simulation testbed for a grid-connected hybrid power system (wind turbine, PV cells, SOFC, electrolyzer, battery storage system, supercapacitor (SC), micro-turbine (MT) and domestic load) is developed in Matlab/Simulink. The robustness and superiority of the proposed indirect adaptive control paradigm are evaluated through simulation results in a grid-connected hybrid power system testbed by comparison with a conventional PI (proportional and integral) control system. The simulation results verify the effectiveness of the proposed control paradigm.

  13. Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury.

    Science.gov (United States)

    Hu, JiangWei; Yang, ZaiLiang; Wang, Jun; Tang, YongYong; Liu, Hao; Zhang, Bin; Chen, Hu

    2013-01-01

    A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC) assay, a hydrogen peroxide (H2O2) content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline) that were exposed to 4.5 Gy (60)Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-)CD117(+): hucMSC-Trx-1 vs. hucMSC, Pgene and cell therapy as a multifunctional radioprotector for ARI.

  14. Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering.

    Science.gov (United States)

    Steinmetz, Neven J; Aisenbrey, Elizabeth A; Westbrook, Kristofer K; Qi, H Jerry; Bryant, Stephanie J

    2015-07-01

    A bioinspired multi-layer hydrogel was developed for the encapsulation of human mesenchymal stem cells (hMSCs) as a platform for osteochondral tissue engineering. The spatial presentation of biochemical cues, via incorporation of extracellular matrix analogs, and mechanical cues, via both hydrogel crosslink density and externally applied mechanical loads, were characterized in each layer. A simple sequential photopolymerization method was employed to form stable poly(ethylene glycol)-based hydrogels with a soft cartilage-like layer of chondroitin sulfate and low RGD concentrations, a stiff bone-like layer with high RGD concentrations, and an intermediate interfacial layer. Under a compressive load, the variation in hydrogel stiffness within each layer produced high strains in the soft cartilage-like layer, low strains in the stiff bone-like layer, and moderate strains in the interfacial layer. When hMSC-laden hydrogels were cultured statically in osteochondral differentiation media, the local biochemical and matrix stiffness cues were not sufficient to spatially guide hMSC differentiation after 21 days. However dynamic mechanical stimulation led to differentially high expression of collagens with collagen II in the cartilage-like layer, collagen X in the interfacial layer and collagen I in the bone-like layer and mineral deposits localized to the bone layer. Overall, these findings point to external mechanical stimulation as a potent regulator of hMSC differentiation toward osteochondral cellular phenotypes.

  15. MSc degree in color technology for the automotive sector

    Science.gov (United States)

    Martinez-Verdu, F.; Perales, E.; Chorro, E.; Viqueira, V.; Gilabert, E.

    2014-07-01

    Nowadays, the measurement and management of color quality of the gonio-apparent materials is complex, but highly demanded in many industrial sectors, as automotive, cosmetics, plastics for consumer electronics, printing inks, architectural coatings, etc. It is necessary to control complex instrumentation and to do visual assessments of texture and color differences to get, for instance, a visual harmony in car bodies; and a profound knowledge of physics and chemistry of special-effect pigments for their optical formulation to obtain attractive visual effects in coatings, plastics, etc, combining among them and with solid pigments. From University of Alicante, for the academic year 2013-14, we are organizing the first MSc degree in Color Technology for the Automotive Sector, with a design of contents embracing CIE colorimetry and visual perception, included the AUDI2000 color difference formula, instrumentation and color management software, fundamentals of coatings and plastics in the automotive sector, and, optical formulation of pigments. The MSc syllabus, with 60 ECTS, is designed to be taught in two semesters: from September to February with on classroom theoretical and practical activities, and, from March to June at virtual level, with internships of training in some companies. Therefore, the MSc Thesis would be the performance report during the internship in companies or research institutions. Some multinational companies, both as car makers and coatings and plastics providers, from European and non-European countries have already shown their support and interest in welcoming students for specific training, even some job offers when the first MSc edition finishes.

  16. MSc Agriculture students working with ex-campus stakeholders

    DEFF Research Database (Denmark)

    Langer, Vibeke; Lund, Mogens; Bendevis, Mira Arpe

    2014-01-01

    In the MSc program in Agriculture at University of Copenhagen we experience that both domestic and international students increasingly enter the programme without a contextual background of “agriculture” and with solid, but fragmented disciplinary and applied knowledge acquired in other courses...

  17. Fit for purpose? Evaluation of an MSc. in Medical Physics.

    LENUS (Irish Health Repository)

    van der Putten, W J

    2014-05-01

    The National University of Ireland in Galway established a Master in Science (MSc.) program in medical physics in 2002. The course was designed to be 90 ECTS(1) credits and of one calendar year duration. From the outset the MSc. was designed to be part of an overall medical physics training program. MSc. programs are now widely used as part of the training and education of medical physicists. There is however paucity of data on the effectiveness of such courses and the purpose of the study reported here is to provide information on one particular MSc. course in medical physics. This is relevant to medical physicists who are involved in the development and running of medical physics training programs. The study used as methodology the Kirkpatrick levels of professional training. It was conducted through an online survey, both from students who graduated from the course and from students who were in the process of completing the course. The survey proved to be an effective way to determine attributes of modules such as learning outcomes, knowledge imparted, quality of teaching materials and others. The survey proved to be remarkably able to demonstrate interventions in the individual course modules. Although the course was shown to be effective in the imparting of the knowledge required to become a qualified medical physicist several areas for improvement were identified. These are mainly in the areas of increased practical experience and in course delivery.

  18. Student performance in a newly developed MSc programme

    DEFF Research Database (Denmark)

    Richelsen, Ann Bettina

    2011-01-01

    The Technical University of Denmark (DTU) offers, as a consequence of the Bologna Declaration, international Master of Science in Engineering (MSc) programmes. Thereby, one of the challenges for DTU is to evaluate international applicants with an educational engineering background and traditions...

  19. M.Sc. in Civil and Structural Engineering

    DEFF Research Database (Denmark)

    The catalogue contain a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short candidate projects as well as regular 3rd semester...... projects at the M.Sc. programme in Civil and Structural Engineering....

  20. M.Sc. in Civil and Structural Engineering

    DEFF Research Database (Denmark)

    The following pages contain a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short master projects as well as regular 3rd...... semester projects at the M.Sc. programme in Civil and Structural Engineering....

  1. M.Sc. in Civil and Structural Engineering

    DEFF Research Database (Denmark)

    This catalogue contains a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short candidate projects as well as regular 3rd...... semester projects at the M.Sc. programme in Civil and Structural Engineering....

  2. M.Sc. in Civil and Structural Engineering

    DEFF Research Database (Denmark)

    Clausen, Johan

    The report contain a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short candidate projects as well as regular 3rd semester...... projects at the M.Sc. programme in Civil and Structural Engineering....

  3. The Application of MSC POOL Technology in Mobile Communication%MSC POOL技术在移动通信中的应用

    Institute of Scientific and Technical Information of China (English)

    昂松鹤

    2014-01-01

    该文通过对MSC Pool技术介绍与优势的分析,阐明MSC Pool在软交换组网中的应用的重要性,分析了MSC POOL技术的关键点以及未来发展趋势,说明了MSC pool的实现方式、优缺点等问题。并对未来网络的展望。%This paper clarifies the importance of the use of MSC Pool in softswitch network through the introduction of MSC Pool and the analysis of its advantage. The paper also analyses the key points of MSC POOL and predicts its trend, which de-scribes its realization methods as well as its benefits and limits. At the end of this paper it looks ahead to the future of network.

  4. Mesenchymal stem/stromal cells: a new ''cells as drugs'' paradigm. Efficacy and critical aspects in cell therapy.

    Science.gov (United States)

    de Girolamo, Laura; Lucarelli, Enrico; Alessandri, Giulio; Avanzini, Maria Antonietta; Bernardo, Maria Ester; Biagi, Ettore; Brini, Anna Teresa; D'Amico, Giovanna; Fagioli, Franca; Ferrero, Ivana; Locatelli, Franco; Maccario, Rita; Marazzi, Mario; Parolini, Ornella; Pessina, Augusto; Torre, Maria Luisa; Italian Mesenchymal Stem Cell Group

    2013-01-01

    Mesenchymal stem cells (MSCs) were first isolated more than 50 years ago from the bone marrow. Currently MSCs may also be isolated from several alternative sources and they have been used in more than a hundred clinical trials worldwide to treat a wide variety of diseases. The MSCs mechanism of action is undefined and currently under investigation. For in vivo purposes MSCs must be produced in compliance with good manufacturing practices and this has stimulated research on MSCs characterization and safety. The objective of this review is to describe recent developments regarding MSCs properties, physiological effects, delivery, clinical applications and possible side effects.

  5. Mesenchymal Stem/Stromal Cells: A New "Cells as Drugs" Paradigm. Efficacy and Critical Aspects in Cell Therapy

    Science.gov (United States)

    de Girolamo, Laura; Lucarelli, Enrico; Alessandri, Giulio; Avanzini, Maria Antonietta; Bernardo, Maria Ester; Biagi, Ettore; Brini, Anna Teresa; D’Amico, Giovanna; Fagioli, Franca; Ferrero, Ivana; Locatelli, Franco; Maccario, Rita; Marazzi, Mario; Parolini, Ornella; Pessina, Augusto; Torre, Maria Luisa

    2013-01-01

    Mesenchymal stem cells (MSCs) were first isolated more than 50 years ago from the bone marrow. Currently MSCs may also be isolated from several alternative sources and they have been used in more than a hundred clinical trials worldwide to treat a wide variety of diseases. The MSCs mechanism of action is undefined and currently under investigation. For in vivo purposes MSCs must be produced in compliance with good manufacturing practices and this has stimulated research on MSCs characterization and safety. The objective of this review is to describe recent developments regarding MSCs properties, physiological effects, delivery, clinical applications and possible side effects. PMID:23278600

  6. Vascularization and restoration of heart function in rat myocardial infarction using transplantation of human cbMSC/HUVEC core-shell bodies.

    Science.gov (United States)

    Lee, Wen-Yu; Wei, Hao-Ji; Wang, Jiun-Jie; Lin, Kun-Ju; Lin, Wei-Wen; Chen, Ding-Yuan; Huang, Chieh-Cheng; Lee, Ting-Yin; Ma, Hsiang-Yang; Hwang, Shiaw-Min; Chang, Yen; Sung, Hsing-Wen

    2012-03-01

    Cell transplantation is a promising strategy for therapeutic treatment of ischemic heart diseases. In this study, cord blood mesenchymal stem cells (cbMSCs) and human umbilical vein endothelial cells (HUVECs) in the form of core-shell bodies (cbMSC/HUVEC bodies) were prepared to promote vascularization and restore heart functions in an experimentally-created myocardial infarction (MI) rat model. Saline, cbMSC bodies and HUVEC bodies were used as controls. In vitro results indicated that cbMSC/HUVEC bodies possessed the capability of heterotypic assembly of cbMSCs and HUVECs into robust and durable tubular networks on Matrigel. The up-regulated gene expressions of VEGF and IGF-1 reflected the robust expansion of tubular networks; in addition, the augmented levels of SMA and SM22 suggested smooth muscle differentiation of cbMSCs, possibly helping to improve the durability of networks. Moreover, according to the in vivo echocardiographic, magnetic resonance and computed-tomographic results, transplantation of cbMSC/HUVEC bodies benefited post-MI dysfunction. Furthermore, the vascularization analyses demonstrated the robust vasculogenic potential of cbMSC/HUVEC bodies in vivo, thus contributing to the greater viable myocardium and the less scar region, and ultimately restoring the cardiac function. The concept of core-shell bodies composed of perivascular cells and endothelial cells may serve as an attractive cell delivery vehicle for vasculogenesis, thus improving the cardiac function significantly.

  7. Genetic polymorphisms and non-small-cell lung cancer: future paradigms

    Energy Technology Data Exchange (ETDEWEB)

    Mello, Ramon Andrade Bezerra de [Serviço de Oncologia Médica, Instituto Português de Oncologia Francisco Gentil, Porto (Portugal); Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, Faro (Portugal)

    2014-07-01

    This article addresses some current issues about genetic polymorphisms studied in the non-small-cell lung cancer translational field. Furthermore, it discusses about new potential biomarkers regarding lung cancer risk and prognosis.

  8. The T helper type 17/regulatory T cell paradigm in pregnancy.

    Science.gov (United States)

    Figueiredo, Ana Sofia; Schumacher, Anne

    2016-05-01

    T helper type 17 (Th17) and regulatory T (Treg) cells are active players in the establishment of tolerance and defence. These attributes of the immune system enmesh to guarantee the right level of protection. The healthy immune system, on the one hand, recognizes and eliminates dangerous non-self pathogens and, on the other hand, protects the healthy self. However, there are circumstances where this fine balance is disrupted. In fact, in situations such as in pregnancy, the foreign fetal antigens challenge the maternal immune system and Treg cells will dominate Th17 cells to guarantee fetal survival. In other situations such as autoimmunity, where the Th17 responses are often overwhelming, the immune system shifts towards an inflammatory profile and attacks the healthy tissue from the self. Interestingly, autoimmune patients have meliorating symptoms during pregnancy. This connects with the antagonist role of Th17 and Treg cells, and their specific profiles during these two immune challenging situations. In this review, we put into perspective the Th17/Treg ratio during pregnancy and autoimmunity, as well as in pregnant women with autoimmune conditions. We further review existing systems biology approaches that study specific mechanisms of these immune cells using mathematical modelling and we point out possible future directions of investigation. Understanding what maintains or disrupts the balance between these two opponent yet reciprocal cells in healthy physiological settings, sheds light into the development of innovative pharmacological approaches to fight pregnancy loss and autoimmunity.

  9. Using PAFEC as a preprocessor for MSC/NASTRAN

    Energy Technology Data Exchange (ETDEWEB)

    Gray, W.H.; Baudry, T.V.

    1983-01-01

    Programs for Automatic Finite Element Calculations (PAFEC) is a general-purpose, three-dimensional, linear and nonlinear finite element program. PAFEC's features include free-format input using engineering keywords, powerful mesh-generating facilities, sophisticated database management procedures, and extensive data validation checks. Presented here is a description of a software interface that permits PAFEC to be used as a preprocessor for MSC/NASTRAN. This user-friendly software, called PAFMSC, frees the stress analyst from the laborious and error-prone procedure of creating and debugging a rigid-format MSC/NASTRAN bulk data deck. By interactively creating and debugging a finite element model with PAFEC, thus taking full advantage of the free-format, engineering-keyword-oriented data structure of PAFEC, the stress analyst can drastically reduce the amount of time spent during model generation. The PAFMSC software will automatically convert a PAFEC data structure into an MSC/NASTRAN bulk data deck. The capabilities and limitations of the PAFMSC software are fully discussed in the following report.

  10. Lactococcus lactis Uses MscL as Its Principal Mechanosensitive Channel

    NARCIS (Netherlands)

    Folgering, Joost H.A.; Moe, Paul C.; Schuurman-Wolters, Gea K.; Blount, Paul; Poolman, Bert

    2005-01-01

    The functions of the mechanosensitive channels from Lactococcus lactis were determined by biochemical, physiological, and electrophysiological methods. Patchclamp studies showed that the genes yncB and mscL encode MscS and MscL-like channels, respectively, when expressed in Escherichia coli or if th

  11. Transport across the cell-membrane dictates nanoparticle fate and toxicity: a new paradigm in nanotoxicology

    Science.gov (United States)

    Guarnieri, Daniela; Sabella, Stefania; Muscetti, Ornella; Belli, Valentina; Malvindi, Maria Ada; Fusco, Sabato; de Luca, Elisa; Pompa, Pier Paolo; Netti, Paolo A.

    2014-08-01

    The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions.The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions. Electronic supplementary information (ESI) available. See DOI

  12. Influence of electrospun fiber mesh size on hMSC oxygen metabolism in 3D collagen matrices: experimental and theoretical evidences.

    Science.gov (United States)

    Guaccio, Angela; Guarino, Vincenzo; Perez, Marco A Alvarez-; Cirillo, Valentina; Netti, Paolo A; Ambrosio, Luigi

    2011-08-01

    The traditional paradigm of tissue engineering of regenerating in vitro tissue or organs, through the combination of an artificial matrix and a cellular population has progressively changed direction. The most recent concept is the realization of a fully functional biohybrid, where both, the artificial and the biotic phase, concur in the formation of the novel organic matter. In this direction, interest is growing in approaches taking advantage of the control at micro- and nano-scale of cell material interaction based on the realization of elementary tassels of cells and materials which constitute the beginning point for the expansion of 3D more complex structures. Since a spontaneous assembly of all these components is expected, however, it becomes more fundamental than ever to define the features influencing cellular behavior, either they were material functional properties, or material architecture. In this work, it has been investigated the direct effect of electrospun fiber sizes on oxygen metabolism of h-MSC cells, when any other culture parameter was kept constant. To this aim, thin PCL electrospun membranes, with micro- and nano-scale texturing, were layered between two collagen slices up to create a sandwich structure (µC-PCL-C and nC-PCL-C). Cells were seeded on membranes, and the oxygen consumption was determined by a phosphorescence quenching technique. Results indicate a strong effect of the architecture of scaffolds on cell metabolism, also revealed by the increasing of HIF1-α gene expression in nC-PCL-C. These findings offer new insights into the role of materials in specific cell activities, also implying the existence of very interesting criteria for the control of tissue growth through the tuning of scaffold architecture.

  13. Application of MSC POOL Technology in the Mobile Softswitch Network%MSC POOL技术在移动软交换组网中的应用

    Institute of Scientific and Technical Information of China (English)

    韩东红

    2014-01-01

    The application of MSC Pool in mobile softswitch network is very important. Its technology is the future development trend of softswitch. This article illustrates the application of MSC POOL and its advantages and disadvantages.%MSC POOL在移动软交换组网应用中非常重要,它的技术是未来软交换发展的趋势。本文说明MSC POOL的应用及优缺点等。

  14. Cancer immunotherapy: a future paradigm shift in the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Anagnostou, Valsamo K; Brahmer, Julie R

    2015-03-01

    Emerging evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy even for tumors that were historically considered as nonimmunogenic. Immunotherapy is emerging as a major modality in non-small cell lung cancer (NSCLC) treatment focusing on vaccine approaches to elicit specific immune responses and development of inhibitors of the molecular mediators of cancer-induced immunosuppression (immune checkpoints) to boost antitumor immune responses. Amplification of the host response against evolving tumors through vaccination is being investigated in ongoing clinical trials with tumor cell vaccines; however, the clinical efficacy of these agents has been limited. Blocking inhibitory pathways such as the CTL antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) checkpoint pathways with mAbs has generated antitumor immune responses that are transforming cancer therapeutics. PD-1 and programmed cell death ligand 1 (PD-L1) antibodies have shown durable responses in NSCLC, with a favorable safety profile and manageable side effects. The activity of immune checkpoint inhibitors is currently been assessed in treatment-naïve patients with PD-L1-positive advanced NSCLC. Combinatorial approaches with other immune checkpoint inhibitors, chemotherapy, or targeted agents are being explored in ongoing clinical trials, and may improve outcome in NSCLC.

  15. Hormonal induction of an immediate-early gene response in myogenic cell lines--a paradigm for heart growth.

    Science.gov (United States)

    Maass, A; Grohé, C; Kubisch, C; Wollnik, B; Vetter, H; Neyses, L

    1995-05-01

    Cardiac hypertrophy is characterized by growth of myocardial cells without proliferation. Many endo- paracrine stimuli such as angiotensin II, endothelin, alpha 1-adrenergic agonists, and insulin have been shown to be able to induce cardiac hypertrophy either in vivo or in vitro. We have used the myoblast model of differentiation and proliferation to determine nuclear signal transduction mechanisms in muscle and (by analogy) cardiac growth. The first nuclear event known to occur when a growth stimulus acts upon a cell is induction of a family of immediate-early genes. Our group focused on the role of one of these genes, the early growth response gene-1 (Egr-1). We have shown that this gene is induced in isolated adult cardiac myocytes in the presence of endothelin. An anti-sense oligonucleotide complementary to the first six codons of the Egr-1 mRNA abolishes the stimulation of protein synthesis induced by endothelin. In the present study we further characterized paracrine growth stimuli in the myogenic cell line Sol8, which was used as a paradigm to further investigate mechanisms of paracrine growth induction. We demonstrated that a variety of candidate endo- paracrine stimuli for the induction of cardiac hypertrophy induced the Egr-1 messenger RNA in the myogenic cell line Sol8. Among these are endothelin, insulin, basic fibroblast growth factor, and platelet-derived growth factor BB (PDGF BB). We conclude: (1) In analogy to the myocardium, these growth factors act upon myoblasts. (2) This line appears to be a suitable model for the molecular characterization of Egr-1 target genes.

  16. Paternal age and telomere length in twins: the germ stem cell selection paradigm.

    Science.gov (United States)

    Hjelmborg, Jacob B; Dalgård, Christine; Mangino, Massimo; Spector, Tim D; Halekoh, Ulrich; Möller, Sören; Kimura, Masayuki; Horvath, Kent; Kark, Jeremy D; Christensen, Kaare; Kyvik, Kirsten O; Aviv, Abraham

    2015-08-01

    Telomere length, a highly heritable trait, is longer in offspring of older fathers. This perplexing feature has been attributed to the longer telomeres in sperm of older men and it might be an 'epigenetic' mechanism through which paternal age plays a role in telomere length regulation in humans. Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, which is not seen in monozygotic twins. This phenomenon might result from a paternal age-dependent germ stem cell selection process, whereby the selected stem cells have longer telomeres, are more homogenous with respect to telomere length, and share resistance to aging.

  17. Muse Cells: Nontumorigenic Pluripotent Stem Cells Present in Adult Tissues—A Paradigm Shift in Tissue Regeneration and Evolution

    OpenAIRE

    Simerman, Ariel A; Julia D. Phan; Dumesic, Daniel A; Chazenbalk, Gregorio D.

    2016-01-01

    Muse cells are a novel population of nontumorigenic pluripotent stem cells, highly resistant to cellular stress. These cells are present in every connective tissue and intrinsically express pluripotent stem markers such as Nanog, Oct3/4, Sox2, and TRA1-60. Muse cells are able to differentiate into cells from all three embryonic germ layers both spontaneously and under media-specific induction. Unlike ESCs and iPSCs, Muse cells exhibit low telomerase activity and asymmetric division and do not...

  18. Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

    Directory of Open Access Journals (Sweden)

    Junghans Richard

    2010-06-01

    Full Text Available Abstract Gene therapy techniques are being applied to modify T cells with chimeric antigen receptors (CARs for therapeutic ends. The versatility of this platform has spawned multiple options for their application with new permutations in strategies continually being invented, a testimony to the creative energies of many investigators. The field is rapidly expanding with immense potential for impact against diverse cancers. But this rapid expansion, like the Big Bang, comes with a somewhat chaotic evolution of its therapeutic universe that can also be dangerous, as seen by recently publicized deaths. Time-honored methods for new drug testing embodied in Dose Escalation that were suitable for traditional inert agents are now inadequate for these novel "living drugs". In the following, I propose an approach to escalating risk for patient exposures with these new immuno-gene therapy agents, termed Strategy Escalation, that accounts for the molecular and biological features of the modified cells and the methods of their administration. This proposal is offered not as a prescriptive but as a discussion framework that investigators may wish to consider in configuring their intended clinical applications.

  19. Nanoprecipitated catestatin released from pharmacologically active microcarriers (PAMs) exerts pro-survival effects on MSC.

    Science.gov (United States)

    Angotti, C; Venier-Julienne, M C; Penna, C; Femminò, S; Sindji, L; Paniagua, C; Montero-Menei, C N; Pagliaro, P

    2016-11-22

    Catestatin (CST), a fragment of Chromogranin-A, exerts angiogenic, arteriogenic, vasculogenic and cardioprotective effects. CST is a very promising agent for revascularization purposes, in "NOOPTION" patients. However, peptides have a very short half-life after administration and must be conveniently protected. Fibronectin-coated pharmacologically active microcarriers (FN-PAM), are biodegradable and biocompatible polymeric microspheres that can convey mesenchymal stem cell (MSCs) and therapeutic proteins delivered in a prolonged manner. In this study, we first evaluated whether a small peptide such as CST could be nanoprecipitated and incorporated within FN-PAMs. Subsequently, whether CST may be released in a prolonged manner by functionalized FN-PAMs (FN-PAM-CST). Finally, we assessed the effect of CST released by FN-PAM-CST on the survival of MSCs under stress conditions of hypoxia-reoxygenation. An experimental design, modifying three key parameters (ionic strength, mixing and centrifugation time) of protein nanoprecipitation, was used to define the optimum condition for CST. An optimal nanoprecipitation yield of 76% was obtained allowing encapsulation of solid CST within FN-PAM-CST, which released CST in a prolonged manner. In vitro, MSCs adhered to FN-PAMs, and the controlled release of CST from FN-PAM-CST greatly limited hypoxic MSC-death and enhanced MSC-survival in post-hypoxic environment. These results suggest that FN-PAM-CST are promising tools for cell-therapy.

  20. "String theory" of c-kit(pos) cardiac cells: a new paradigm regarding the nature of these cells that may reconcile apparently discrepant results.

    Science.gov (United States)

    Keith, Matthew C L; Bolli, Roberto

    2015-03-27

    Although numerous preclinical investigations have consistently demonstrated salubrious effects of c-kit(pos) cardiac cells administered after myocardial infarction, the mechanism of action remains highly controversial. We and others have found little or no evidence that these cells differentiate into mature functional cardiomyocytes, suggesting paracrine effects. In this review, we propose a new paradigm predicated on a comprehensive analysis of the literature, including studies of cardiac development; we have (facetiously) dubbed this conceptual construct "string theory" of c-kit(pos) cardiac cells because it reconciles multifarious and sometimes apparently discrepant results. There is strong evidence that, during development, the c-kit receptor is expressed in different pools of cardiac progenitors (some capable of robust cardiomyogenesis and others with little or no contribution to myocytes). Accordingly, c-kit positivity, in itself, does not define the embryonic origins, lineage capabilities, or differentiation capacities of specific cardiac progenitors. C-kit(pos) cells derived from the first heart field exhibit cardiomyogenic potential during development, but these cells are likely depleted shortly before or after birth. The residual c-kit(pos) cells found in the adult heart are probably of proepicardial origin, possess a mesenchymal phenotype (resembling bone marrow mesenchymal stem/stromal cells), and are capable of contributing significantly only to nonmyocytic lineages (fibroblasts, smooth muscle cells, and endothelial cells). If these 2 populations (first heart field and proepicardium) express different levels of c-kit, the cardiomyogenic potential of first heart field progenitors might be reconciled with recent results of c-kit(pos) cell lineage tracing studies. The concept that c-kit expression in the adult heart identifies epicardium-derived, noncardiomyogenic precursors with a mesenchymal phenotype helps to explain the beneficial effects of c

  1. A mechanistic paradigm for broad-spectrum antivirals that target virus-cell fusion.

    Directory of Open Access Journals (Sweden)

    Frederic Vigant

    Full Text Available LJ001 is a lipophilic thiazolidine derivative that inhibits the entry of numerous enveloped viruses at non-cytotoxic concentrations (IC50 ≤ 0.5 µM, and was posited to exploit the physiological difference between static viral membranes and biogenic cellular membranes. We now report on the molecular mechanism that results in LJ001's specific inhibition of virus-cell fusion. The antiviral activity of LJ001 was light-dependent, required the presence of molecular oxygen, and was reversed by singlet oxygen ((1O2 quenchers, qualifying LJ001 as a type II photosensitizer. Unsaturated phospholipids were the main target modified by LJ001-generated (1O2. Hydroxylated fatty acid species were detected in model and viral membranes treated with LJ001, but not its inactive molecular analog, LJ025. (1O2-mediated allylic hydroxylation of unsaturated phospholipids leads to a trans-isomerization of the double bond and concurrent formation of a hydroxyl group in the middle of the hydrophobic lipid bilayer. LJ001-induced (1O2-mediated lipid oxidation negatively impacts on the biophysical properties of viral membranes (membrane curvature and fluidity critical for productive virus-cell membrane fusion. LJ001 did not mediate any apparent damage on biogenic cellular membranes, likely due to multiple endogenous cytoprotection mechanisms against phospholipid hydroperoxides. Based on our understanding of LJ001's mechanism of action, we designed a new class of membrane-intercalating photosensitizers to overcome LJ001's limitations for use as an in vivo antiviral agent. Structure activity relationship (SAR studies led to a novel class of compounds (oxazolidine-2,4-dithiones with (1 100-fold improved in vitro potency (IC50<10 nM, (2 red-shifted absorption spectra (for better tissue penetration, (3 increased quantum yield (efficiency of (1O2 generation, and (4 10-100-fold improved bioavailability. Candidate compounds in our new series moderately but significantly (p≤0

  2. The role of dendritic cells in alphaherpesvirus infections: archetypes and paradigms.

    Science.gov (United States)

    Van de Walle, Gerlinde R; Cox, Eric; Nauwynck, Hans; Favoreel, Herman W

    2009-11-01

    Dendritic cells (DCs) play a critical role in orchestrating both innate and adaptive components of the immune system and are therefore of pivotal importance in the initiation of immune responses to control and eliminate viral infections. A major focus of this review is to give an overview on the recent findings that point out the importance of DCs in controlling alphaherpesvirus infections, but also indicate that these viruses have evolved several strategies to inhibit and/or exploit DC functions to delay or escape elimination by the immune system. In addition, we point out the common features and interspecies differences between DCs from man and animal, and discuss the potential use of animal alphaherpesvirus homologues to gain further insights into the interaction between alphaherpesviruses and DCs in their natural virus-host environment. Finally, recent knowledge on the potential of alphaherpesviruses as vectors for DC stimulation and their use for immunotherapy is presented.

  3. Muse Cells: Nontumorigenic Pluripotent Stem Cells Present in Adult Tissues—A Paradigm Shift in Tissue Regeneration and Evolution

    Directory of Open Access Journals (Sweden)

    Ariel A. Simerman

    2016-01-01

    Full Text Available Muse cells are a novel population of nontumorigenic pluripotent stem cells, highly resistant to cellular stress. These cells are present in every connective tissue and intrinsically express pluripotent stem markers such as Nanog, Oct3/4, Sox2, and TRA1-60. Muse cells are able to differentiate into cells from all three embryonic germ layers both spontaneously and under media-specific induction. Unlike ESCs and iPSCs, Muse cells exhibit low telomerase activity and asymmetric division and do not undergo tumorigenesis or teratoma formation when transplanted into a host organism. Muse cells have a high capacity for homing into damaged tissue and spontaneous differentiation into cells of compatible tissue, leading to tissue repair and functional restoration. The ability of Muse cells to restore tissue function may demonstrate the role of Muse cells in a highly conserved cellular mechanism related to cell survival and regeneration, in response to cellular stress and acute injury. From an evolutionary standpoint, genes pertaining to the regenerative capacity of an organism have been lost in higher mammals from more primitive species. Therefore, Muse cells may offer insight into the molecular and evolutionary bases of autonomous tissue regeneration and elucidate the molecular and cellular mechanisms that prevent mammals from regenerating limbs and organs, as planarians, newts, zebrafish, and salamanders do.

  4. Muse Cells: Nontumorigenic Pluripotent Stem Cells Present in Adult Tissues—A Paradigm Shift in Tissue Regeneration and Evolution

    Science.gov (United States)

    2016-01-01

    Muse cells are a novel population of nontumorigenic pluripotent stem cells, highly resistant to cellular stress. These cells are present in every connective tissue and intrinsically express pluripotent stem markers such as Nanog, Oct3/4, Sox2, and TRA1-60. Muse cells are able to differentiate into cells from all three embryonic germ layers both spontaneously and under media-specific induction. Unlike ESCs and iPSCs, Muse cells exhibit low telomerase activity and asymmetric division and do not undergo tumorigenesis or teratoma formation when transplanted into a host organism. Muse cells have a high capacity for homing into damaged tissue and spontaneous differentiation into cells of compatible tissue, leading to tissue repair and functional restoration. The ability of Muse cells to restore tissue function may demonstrate the role of Muse cells in a highly conserved cellular mechanism related to cell survival and regeneration, in response to cellular stress and acute injury. From an evolutionary standpoint, genes pertaining to the regenerative capacity of an organism have been lost in higher mammals from more primitive species. Therefore, Muse cells may offer insight into the molecular and evolutionary bases of autonomous tissue regeneration and elucidate the molecular and cellular mechanisms that prevent mammals from regenerating limbs and organs, as planarians, newts, zebrafish, and salamanders do. PMID:28070194

  5. MSc Science Communication, Science Communication Unit, UWE, Bristol

    Directory of Open Access Journals (Sweden)

    C. Wilkinson

    2009-03-01

    Full Text Available The MSc in Science Communication offered by the University of the West of England is taught in short three day blocks, designed specifically to cater for both full and part time students wishing to combine work and study effectively. Started in 2004, the programme emphasises the development of practical skills as well as developing a wider understanding of the key issues facing science communicators today. With this in mind, workshops explore theory and practice, considering the potential of a range of creative, targeted and innovative opportunities to enable greater community participation in scientific issues.

  6. Sarcomas as a mise en abyme of mesenchymal stem cells: exploiting interrelationships for cell mediated anticancer therapy

    DEFF Research Database (Denmark)

    Burns, Jorge S; Safwat, Akmal; Grisendi, Giulia;

    2012-01-01

    Mise en abyme meaning "placed into abyss or infinite recurrence" is an apt paradigm for the relentless growth of sarcoma cells. Its alternative meaning, "self-reflexive embedding" fits the central role attributed to cancer stem cells (CSCs). Diversely sourced and defined, mesenchymal stem cells...... (MSCs) may be the cells of sarcoma origin, evolve a CSC phenotype and/or contribute to tumor growth through inherent qualities for homing, neovascularization, paracrine cross-feeding, microvesicle secretion, cell fusion, entosis and immune modulation. Exploiting these qualities, MSC expressing modified...

  7. 基于MSC POOL实现SERVER容灾的方案研究

    Institute of Scientific and Technical Information of China (English)

    徐萍

    2014-01-01

    本文简要介绍了MSC POOL的演进背景、MSC POOL的概念、容灾,并以新疆移动为例,着重从容灾实现方案的组网、数据准备、实施验证等三方面介绍了基于MSC POOL实现SERVER容灾的方案研究。

  8. Research on Load Transfer Method and Application of MSC Pool%MSC Pool负荷迁移机制及应用研究

    Institute of Scientific and Technical Information of China (English)

    黄华生

    2011-01-01

    针对常规MSC Pool负荷迁移后存在的MSC Pool中各MSC间负荷仍不均衡的情况,创立了基于话务模型的数据预测和多次迭代算法的迁移流程,实现了MSC Pool内的负荷均衡,并通过网管程序实现了负荷不均衡自动监测和负荷自动调整.

  9. M.Sc. in Civil and Structural Engineering

    DEFF Research Database (Denmark)

    Clausen, Johan Christian

    The following pages contain a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short master projects as well as regular 3rd...... semester projects at the M.Sc. programme in Civil and Structural Engineering. Each project description provides a brief overview of the purpose as well as the main activities. Further, a weighting between theoretical analysis, experimental work and computer modelling has been proposed. Usually...... page. Furthermore, other ideas for projects may be discussed with a potential supervisor. Many private engineering companies have a homepage on which they state that they would like to collaborate with students on a master project....

  10. A New Paradigm for African American Breast Cancer Involving Stem Cell Differentiation in a Novel Cell Culture System

    Science.gov (United States)

    2006-10-01

    alization of chemotherapy based on some aspect of NER expression is being pursued in colon [42], testicular [43,44] and ovarian cancer [45]. Conclusion... glutathione S-transferase polymorphisms: a case-control study. Cancer Res 2001, 61:8465-8469. 16. Kennedy DO, Agrawal M, Shen J, Terry MB, Zhang FF...damage caused by reduced XPA pro- tein in testicular germ cell tumours. Curr Biol 1999, 9:273-276. 45. Selvakumaran M, Pisarcik DA, Bao R, Yeung AT

  11. Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice.

    Directory of Open Access Journals (Sweden)

    Silvia Mora-Lee

    Full Text Available Stroke represents an attractive target for stem cell therapy. Although different types of cells have been employed in animal models, a direct comparison between cell sources has not been performed. The aim of our study was to assess the effect of human multipotent adult progenitor cells (hMAPCs and human mesenchymal stem cells (hMSCs on endogenous neurogenesis, angiogenesis and inflammation following stroke. BALB/Ca-RAG 2(-/- γC(-/- mice subjected to FeCl(3 thrombosis mediated stroke were intracranially injected with 2 × 10(5 hMAPCs or hMSCs 2 days after stroke and followed for up to 28 days. We could not detect long-term engraftment of either cell population. However, in comparison with PBS-treated animals, hMSC and hMAPC grafted animals demonstrated significantly decreased loss of brain tissue. This was associated with increased angiogenesis, diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced proliferation of cells in the subventricular zone (SVZ and survival of newly generated neuroblasts was observed. Interestingly, these neuroprotective effects were more pronounced in the group of animals treated with hMAPCs in comparison with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a promising strategy for the treatment of stroke.

  12. Physiology and pathophysiology of selectins, integrins, and IgSF cell adhesion molecules focusing on inflammation. A paradigm model on infectious endocarditis.

    Science.gov (United States)

    Golias, Christos; Batistatou, Anna; Bablekos, Georgios; Charalabopoulos, Alexandros; Peschos, Dimitrios; Mitsopoulos, Panagiotis; Charalabopoulos, Konstantinos

    2011-06-01

    The development of adhesion bonds, either among cells or among cells and components of the extracellular matrix, is a crucial process. These interactions are mediated by some molecules collectively known as adhesion molecules (CAMs). CAMs are ubiquitously expressed proteins playing a central role in controlling cell migration, proliferation, survival, and apoptosis. Besides their key function in physiological maintenance of tissue integrity, CAMs play an eminent role in various pathological processes such as cardiovascular disorders, atherogenesis, atherosclerotic plaque progression and regulation of the inflammatory response. CAMs such as selectins, integrins, and immunoglobulin superfamily take part in interactions between leukocyte and vascular endothelium (leukocyte rolling, arrest, firm adhesion, migration). Experimental data and pathologic observations support the assumption that pathogenic microorganisms attach to vascular endothelial cells or sites of vascular injury initiating intravascular infections. In this review a paradigm focusing on cell adhesion molecules pathophysiology and infective endocarditis development is given.

  13. Didaktiske paradigmer og refleksion

    DEFF Research Database (Denmark)

    Christensen, Torben Spanget

    2014-01-01

    this article. A possible utilitarian didactical paradigm, already indicated by Krogh as a historical paradigm prominent in our time, is also discussed. It is suggested that reflection could be seen as a normative response to the utilitarian paradigm, and not as a paradigm in its own right. It is concluded...... that reflection must be understood as an overarching cultural phenomenon and a very important qualification of all Nielsen’s paradigms, and also a possible utilitarian paradigm, because it has the potential to add dynamic elements to the more or less static didactic paradigms. Thus the semiotic analysis may...

  14. Molecular Mechanisms Involved in Mesenchymal Stem Cell Migration to the Site of Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Katarina Kollar

    2009-01-01

    Full Text Available Mesenchymal stem cells or multipotent mesenchymal stromal cells (both referred to as MSC have been shown in some studies to have a beneficial effect on myocardial recovery after infarct. Current strategies for MSC delivery to heart involve intravenous, intraarterial, and intramuscular delivery. Different routes of MSC delivery and a lack of knowledge of the mechanisms that MSC utilise to migrate in vivo has most likely led to the marked variations in results that have been found. This review aims to summarise the current knowledge of MSC migratory mechanisms and looks to future methods of MSC manipulation prior to delivery in order to enhance MSC migration and engraftment.

  15. Curriculum (Study Programme) for the M.Sc., Medialogy, at Aalborg University in Copenhagen

    DEFF Research Database (Denmark)

    Serafin, Stefania; Nordahl, Rolf; Lavatino, Salvatore

    2004-01-01

    Defining and describing the education, M.Sc., Medialogy. The curriculum (Study Programme) describes semesters, themes, projectunits, courses and contents of the eduation. offered at Aalborg University in Copenhagen.......Defining and describing the education, M.Sc., Medialogy. The curriculum (Study Programme) describes semesters, themes, projectunits, courses and contents of the eduation. offered at Aalborg University in Copenhagen....

  16. The ‘devils triangle’ of MSC certification: Balancing credibility, accessibility and continuous improvement

    NARCIS (Netherlands)

    Bush, S.R.; Toonen, H.M.; Oosterveer, P.J.M.; Mol, A.P.J.

    2013-01-01

    The Marine Stewardship Council (MSC) has continued to strengthen its position in the market based on its credibility as a transparent, accountable and science-based third party certification scheme. However, the consolidation of MSC's credibility risks being undermined by the poor representation of

  17. 基于lu_flex的MSC Pool技术分析

    Institute of Scientific and Technical Information of China (English)

    杨波; 樊自甫; 万晓榆

    2008-01-01

    MSC池(MSCin Pool)是由3GPP规范定义的,能优化整个移动网络的组网。本文简要介绍了MSC Pool技术的基本原理及其组网特点,分析了MSC Pool所用到的关键技术(NRI路由机制和负荷分担),重点讨论了核心网D接口信令的流量,根据MSC Pool的技术特点,提出了组网规划的前提条件和规划时需要注意的问题,最后总结了MSC Pool技术的特点,在结论部分给出了MSC Pool可能存在的安全隐患。

  18. CNN a paradigm for complexity

    CERN Document Server

    Chua, Leon O

    1998-01-01

    Revolutionary and original, this treatise presents a new paradigm of EMERGENCE and COMPLEXITY, with applications drawn from numerous disciplines, including artificial life, biology, chemistry, computation, physics, image processing, information science, etc.CNN is an acronym for Cellular Neural Networks when used in the context of brain science, or Cellular Nonlinear Networks, when used in the context of emergence and complexity. A CNN is modeled by cells and interactions: cells are defined as dynamical systems and interactions are defined via coupling laws. The CNN paradigm is a universal Tur

  19. Fetal microchimeric cells in a fetus-treats-its-mother paradigm do not contribute to dystrophin production in serially parous mdx females.

    Science.gov (United States)

    Seppanen, Elke Jane; Hodgson, Samantha Susan; Khosrotehrani, Kiarash; Bou-Gharios, George; Fisk, Nicholas M

    2012-10-10

    Throughout every pregnancy, genetically distinct fetal microchimeric stem/progenitor cells (FMCs) engraft in the mother, persist long after delivery, and may home to damaged maternal tissues. Phenotypically normal fetal lymphoid progenitors have been described to develop in immunodeficient mothers in a fetus-treats-its-mother paradigm. Since stem cells contribute to muscle repair, we assessed this paradigm in the mdx mouse model of Duchenne muscular dystrophy. mdx females were bred serially to either ROSAeGFP males or mdx males to obtain postpartum microchimeras that received either wild-type FMCs or dystrophin-deficient FMCs through serial gestations. To enhance regeneration, notexin was injected into the tibialis anterior of postpartum mice. FMCs were detected by qPCR at a higher frequency in injected compared to noninjected side muscle (P=0.02). However, the number of dystrophin-positive fibers was similar in mothers delivering wild-type compared to mdx pups. In addition, there was no correlation between FMC detection and percentage dystrophin, and no GFP+ve FMCs were identified that expressed dystrophin. In 10/11 animals, GFP+ve FMCs were detected by immunohistochemistry, of which 60% expressed CD45 with 96% outside the basal lamina defining myofiber contours. Finally we confirmed lack of FMC contribution to statellite cells in postpartum mdx females mated with Myf5-LacZ males. We conclude that the FMC contribution to regenerating muscles is insufficient to have a functional impact.

  20. Molecular characterization of heterogeneous mesenchymal stem cells with single-cell transcriptomes.

    Science.gov (United States)

    Li, Zhongjun; Zhang, Chao; Weiner, Leslie P; Zhang, Yiqiang; Zhong, Jiang F

    2013-01-01

    Mesenchymal stem cells (MSC) are heterogeneous cell populations with promising therapeutic potentials in regenerative medicine. The therapeutic values of MSC in various clinical situations have been reported. Clonal assays (expansion of MSC from a single cell) demonstrated that multiple types of cells with different developmental potential exist in a MSC population. Due to the heterogeneous nature of MSC, molecular characterization of MSC in the absence of known biomarkers is a challenge for cell therapy with MSC. Here, we review potential therapeutic applications of MSC and discuss a systematic approach for molecular characterization of heterogeneous cell population using single-cell transcriptome analysis. Differentiation/maturation of cells is orchestrated by sequential expression of a series of genes within a cell. Therefore, single-cell mRNA expression (transcriptome) profiles from consecutive developmental stages are more similar than those from disparate stages. Bioinformatic analysis can cluster single-cell transcriptome profiles from consecutive developmental stages into a dendrogram based on the similarity matrix of these profiles. Because a single-cell is an ultimately "pure" sample in expression profiling, these dendrograms can be used to classify individual cells into molecular subpopulations within a heterogeneous cell population without known biomarkers. This approach is especially powerful in studying cell populations with little molecular information and few known biomarkers, for example the MSC populations. The molecular understanding will provide novel targets for manipulating MSC differentiation with small molecules and other drugs to enable safer and more effective therapeutic applications of MSC.

  1. 包头联通核心网MSC POOL规划案例

    Institute of Scientific and Technical Information of China (English)

    宇文广

    2014-01-01

    通过对MSC POOL原理简要介绍,根据MSC POOL的实施目标及原则,以包头联通网络为例,将包头联通的网络现状作为基础,阐述CS域中MSS设备组POOL的具体实施方案.根据该方案的具体描述可以指导包头联通MSC POOL的建设.

  2. Positioning Theory in Paradigms

    Institute of Scientific and Technical Information of China (English)

    FU Xiao-qiu

    2015-01-01

    This article discusses the importance of theory and paradigm to a researcher. It starts from introducing and analyzing the definition of the two terms, by using the theories in the field of intercultural communication as examples. To a good researcher, he needs not only clarifying the paradigm his research is positioned, but also integrating the theories in his paradigm.

  3. Paradigms of polyamory.

    Science.gov (United States)

    Zambrano, M

    1999-01-01

    SUMMARY The paradigm theory of Thomas Kuhn is used as a framework to discuss alternative ways of intimacy. The author discusses the implications of structuring actual lesbian relationships by a paradigm of monogamy among Latin-American women. The author proposes that creating alternative paradigms of multiple relationships would be useful for many lesbians as models for alternative life patterns.

  4. The impact of the C-terminal domain on the gating properties of MscCG from Corynebacterium glutamicum.

    Science.gov (United States)

    Nakayama, Yoshitaka; Becker, Michael; Ebrahimian, Haleh; Konishi, Tomoyuki; Kawasaki, Hisashi; Krämer, Reinhard; Martinac, Boris

    2016-01-01

    The mechanosensitive (MS) channel MscCG from the soil bacterium Corynebacterium glutamicum functions as a major glutamate exporter. MscCG belongs to a subfamily of the bacterial MscS-like channels, which play an important role in osmoregulation. To understand the structural and functional features of MscCG, we investigated the role of the carboxyl-terminal domain, whose relevance for the channel gating has been unknown. The chimeric channel MscS-(C-MscCG), which is a fusion protein between the carboxyl terminal domain of MscCG and the MscS channel, was examined by the patch clamp technique. We found that the chimeric channel exhibited MS channel activity in Escherichia coli spheroplasts characterized by a lower activation threshold and slow closing compared to MscS. The chimeric channel MscS-(C-MscCG) was successfully reconstituted into azolectin liposomes and exhibited gating hysteresis in a voltage-dependent manner, especially at high pipette voltages. Moreover, the channel remained open after releasing pipette pressure at membrane potentials physiologically relevant for C. glutamicum. This contribution to the gating hysteresis of the C-terminal domain of MscCG confers to the channel gating properties highly suitable for release of intracellular solutes.

  5. Chemotaxis in densely populated tissue determines germinal center anatomy and cell motility: a new paradigm for the development of complex tissues.

    Directory of Open Access Journals (Sweden)

    Jared B Hawkins

    Full Text Available Germinal centers (GCs are complex dynamic structures that form within lymph nodes as an essential process in the humoral immune response. They represent a paradigm for studying the regulation of cell movement in the development of complex anatomical structures. We have developed a simulation of a modified cyclic re-entry model of GC dynamics which successfully employs chemotaxis to recapitulate the anatomy of the primary follicle and the development of a mature GC, including correctly structured mantle, dark and light zones. We then show that correct single cell movement dynamics (including persistent random walk and inter-zonal crossing arise from this simulation as purely emergent properties. The major insight of our study is that chemotaxis can only achieve this when constrained by the known biological properties that cells are incompressible, exist in a densely packed environment, and must therefore compete for space. It is this interplay of chemotaxis and competition for limited space that generates all the complex and biologically accurate behaviors described here. Thus, from a single simple mechanism that is well documented in the biological literature, we can explain both higher level structure and single cell movement behaviors. To our knowledge this is the first GC model that is able to recapitulate both correctly detailed anatomy and single cell movement. This mechanism may have wide application for modeling other biological systems where cells undergo complex patterns of movement to produce defined anatomical structures with sharp tissue boundaries.

  6. Bacterial mechanosensitive channels--MscS: evolution's solution to creating sensitivity in function.

    Science.gov (United States)

    Naismith, James H; Booth, Ian R

    2012-01-01

    The discovery of mechanosensing channels has changed our understanding of bacterial physiology. The mechanosensitive channel of small conductance (MscS) is perhaps the most intensively studied of these channels. MscS has at least two states: closed, which does not allow solutes to exit the cytoplasm, and open, which allows rapid efflux of solvent and solutes. The ability to appropriately open or close the channel (gating) is critical to bacterial survival. We briefly review the science that led to the isolation and identification of MscS. We concentrate on the structure-function relationship of the channel, in particular the structural and biochemical approaches to understanding channel gating. We highlight the troubling discrepancies between the various models developed to understand MscS gating.

  7. Bacterial Mechanosensitive Channels—MscS: Evolution’s Solution to Creating Sensitivity in Function

    Science.gov (United States)

    Naismith, James H.; Booth, Ian R.

    2012-01-01

    The discovery of mechanosensing channels has changed our understanding of bacterial physiology. The mechanosensitive channel of small conductance (MscS) is perhaps the most intensively studied of these channels. MscS has at least two states: closed, which does not allow solutes to exit the cytoplasm, and open, which allows rapid efflux of solvent and solutes. The ability to appropriately open or close the channel (gating) is critical to bacterial survival. We briefly review the science that led to the isolation and identification of MscS. We concentrate on the structure-function relationship of the channel, in particular the structural and biochemical approaches to understanding channel gating. We highlight the troubling discrepancies between the various models developed to understand MscS gating. PMID:22404681

  8. Evidence for Transfer of Membranes from Mesenchymal Stem Cells to HL-1 Cardiac Cells.

    Science.gov (United States)

    Boomsma, Robert A; Geenen, David L

    2014-01-01

    This study examined the interaction of mouse bone marrow mesenchymal stem cells (MSC) with cardiac HL-1 cells during coculture by fluorescent dye labeling and then flow cytometry. MSC were layered onto confluent HL-1 cell cultures in a 1 : 4 ratio. MSC gained gap junction permeant calcein from HL-1 cells after 4 hours which was partially reduced by oleamide. After 20 hours, 99% MSC gained calcein, unaffected by oleamide. Double-labeling HL-1 cells with calcein and the membrane dye DiO resulted in transfer of both calcein and DiO to MSC. When HL-1 cells were labeled with calcein and MSC with DiO, MSC gained calcein while HL-1 cells gained DiO. Very little fusion was observed since more than 90% Sca-1 positive MSC gained DiO from HL-1 cells while less than 9% gained gap junction impermeant CMFDA after 20 hours with no Sca-1 transfer to HL-1 cells. Time dependent transfer of membrane DiD was observed from HL-1 cells to MSC (100%) and vice versa (50%) after 20 hours with more limited transfer of CMFDA. These results demonstrate that MSC and HL-1 cells exchange membrane components which may account for some of the beneficial effect of MSC in the heart after myocardial infarction.

  9. Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats

    OpenAIRE

    2014-01-01

    Background Several lines of evidence have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSC) release bioactive factors and provide neuroprotection for CNS injury. However, it remains elusive whether BM-MSC derived from healthy donors or stroke patients provides equal therapeutic potential. The present work aims to characterize BM-MSC prepared from normal healthy rats (NormBM-MSC) and cerebral ischemia rats (IschBM-MSC), and examine the effects of their conditioned medium (C...

  10. Human mesenchymal stem cells promote survival of T cells in a quiescent state.

    Science.gov (United States)

    Benvenuto, Federica; Ferrari, Stefania; Gerdoni, Ezio; Gualandi, Francesca; Frassoni, Francesco; Pistoia, Vito; Mancardi, Gianluigi; Uccelli, Antonio

    2007-07-01

    Mesenchymal stem cells (MSC) are part of the bone marrow that provides signals supporting survival and growth of bystander hematopoietic stem cells (HSC). MSC modulate also the immune response, as they inhibit proliferation of lymphocytes. In order to investigate whether MSC can support survival of T cells, we investigated MSC capacity of rescuing T lymphocytes from cell death induced by different mechanisms. We observed that MSC prolong survival of unstimulated T cells and apoptosis-prone thymocytes cultured under starving conditions. MSC rescued T cells from activation induced cell death (AICD) by downregulation of Fas receptor and Fas ligand on T cell surface and inhibition of endogenous proteases involved in cell death. MSC dampened also Fas receptor mediated apoptosis of CD95 expressing Jurkat leukemic T cells. In contrast, rescue from AICD was not associated with a significant change of Bcl-2, an inhibitor of apoptosis induced by cell stress. Accordingly, MSC exhibited a minimal capacity of rescuing Jurkat cells from chemically induced apoptosis, a process disrupting the mitochondrial membrane potential regulated by Bcl-2. These results suggest that MSC interfere with the Fas receptor regulated process of programmed cell death. Overall, MSC can inhibit proliferation of activated T cells while supporting their survival in a quiescent state, providing a model of their activity inside the HSC niche. Disclosure of potential conflicts of interest is found at the end of this article.

  11. Chimeras Reveal a Single Lipid-Interface Residue that Controls MscL Channel Kinetics as well as Mechanosensitivity

    Directory of Open Access Journals (Sweden)

    Li-Min Yang

    2013-02-01

    Full Text Available MscL, the highly conserved bacterial mechanosensitive channel of large conductance, serves as an osmotic “emergency release valve,” is among the best-studied mechanosensors, and is a paradigm of how a channel senses and responds to membrane tension. Although all homologs tested thus far encode channel activity, many show functional differences. We tested Escherichia coli and Staphylococcus aureus chimeras and found that the periplasmic region of the protein, particularly E. coli I49 and the equivalent S. aureus F47 at the periplasmic lipid-aqueous interface of the first transmembrane domain, drastically influences both the open dwell time and the threshold of channel opening. One mutant shows a severe hysteresis, confirming the importance of this residue in determining the energy barriers for channel gating. We propose that this site acts similarly to a spring for a clasp knife, adjusting the resistance for obtaining and stabilizing an open or closed channel structure.

  12. The Investment Paradigm

    Science.gov (United States)

    Perna, Mark C.

    2005-01-01

    Is marketing an expense or an investment? Most accountants will claim that marketing is an expense, and clearly that seems true when cutting the checks to fund these efforts. When it is done properly, marketing is the best investment. A key principle to Smart Marketing is the Investment Paradigm. The Investment Paradigm is understanding that every…

  13. Effect of Intrinsic Noise on the Phenotype of Cell Populations Featuring Solution Multiplicity: An Artificial lac Operon Network Paradigm.

    Directory of Open Access Journals (Sweden)

    Ioannis G Aviziotis

    Full Text Available Heterogeneity in cell populations originates from two fundamentally different sources: the uneven distribution of intracellular content during cell division, and the stochastic fluctuations of regulatory molecules existing in small amounts. Discrete stochastic models can incorporate both sources of cell heterogeneity with sufficient accuracy in the description of an isogenic cell population; however, they lack efficiency when a systems level analysis is required, due to substantial computational requirements. In this work, we study the effect of cell heterogeneity in the behaviour of isogenic cell populations carrying the genetic network of lac operon, which exhibits solution multiplicity over a wide range of extracellular conditions. For such systems, the strategy of performing solely direct temporal solutions is a prohibitive task, since a large ensemble of initial states needs to be tested in order to drive the system--through long time simulations--to possible co-existing steady state solutions. We implement a multiscale computational framework, the so-called "equation-free" methodology, which enables the performance of numerical tasks, such as the computation of coarse steady state solutions and coarse bifurcation analysis. Dynamically stable and unstable solutions are computed and the effect of intrinsic noise on the range of bistability is efficiently investigated. The results are compared with the homogeneous model, which neglects all sources of heterogeneity, with the deterministic cell population balance model, as well as with a stochastic model neglecting the heterogeneity originating from intrinsic noise effects. We show that when the effect of intrinsic source of heterogeneity is intensified, the bistability range shifts towards higher extracellular inducer concentration values.

  14. Targeting P38 Pathway Regulates Bony Formation via MSC Recruitment during Mandibular Distraction Osteogenesis in Rats

    Science.gov (United States)

    Yang, Zi-hui; Wu, Bao-lei; Ye, Chen; Jia, Sen; Yang, Xin-jie; Hou, Rui; Lei, De-lin; Wang, Lei

    2016-01-01

    Distraction osteogenesis (DO) is a widely used self-tissue engineering. However, complications and discomfort due to the long treatment period are still the bottleneck of DO. Novel strategies to accelerate bone formation in DO are still needed. P38 is capable of regulating the osteogenic differentiation of both mesenchymal stem cells (MSCs) and osteoblasts, which are crucial to bone regeneration. However, it is not clear whether targeting p38 could regulate bony formation in DO. The purpose of the current work was to investigate the effects of local application of either p38 agonist anisomycin or p38 inhibitor SB203580 in a rat model of DO. 30 adult rats were randomly divided into 3 groups: (A) rats injected with DMSO served as the control group; (B) rats injected with p38 agonist anisomycin; (C) rats injected with p38 inhibitor SB203580. All the rats were subjected to mandibular distraction and the injection was performed daily during this period. The distracted mandibles were harvested on days 15 and 30 after surgery and subjected to the following analysis. Micro-computed tomography and histological evaluation results showed that local application of p38 agonist anisomycin increased new bone formation in DO, whereas p38 inhibitor SB203580 decreased it. Immunohistochemical analysis suggested that anisomycin promoted MSC recruitment in the distraction gap. In conclusion, this study demonstrated that local application of p38 agonist anisomycin can increase new bone formation during DO. This study may lead to a novel cell-based strategy for the improvement of bone regeneration. PMID:27766028

  15. The Marine Stewardship Council (MSC) and the Making of a Market for ‘Sustainable Fish’

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2012-01-01

    Market-based instruments of fishery governance have been promoted in the past two decades on the basis of two widespread expectations: that complying with sustainability standards will lead to environmental benefits; and that certifications will not discriminate against specific social groups......, countries or regions. This paper assesses whether these assumptions hold through the analysis of how the Marine Stewardship Council (MSC) label for capture fisheries has managed ‘supply’, ‘demand’ and ‘civic’ concerns in the market for sustainability certifications. The MSC has created and now dominates...... the market for ‘sustainable fish’, but success has been accompanied by serious challenges. The MSC has so far failed to convincingly show that its certification system has positive environmental impacts, and it has marginalized Southern fisheries, especially in low-income countries. As an institutional...

  16. Defending the future: An MSc module in End User Computing Risk Management

    CERN Document Server

    Thorne, Simon

    2010-01-01

    This paper describes the rationale, curriculum and subject matter of a new MSc module being taught on an MSc Finance and Information Management course at the University of Wales Institute in Cardiff. Academic research on spreadsheet risks now has some penetration in academic literature and there is a growing body of knowledge on the subjects of spreadsheet error, human factors, spreadsheet engineering, "best practice", spreadsheet risk management and various techniques used to mitigate spreadsheet errors. This new MSc module in End User Computing Risk Management is an attempt to pull all of this research and practitioner experience together to arm the next generation of finance spreadsheet champions with the relevant knowledge, techniques and critical perspective on an emerging discipline.

  17. Force transduction and lipid binding in MscL: a continuum-molecular approach.

    Directory of Open Access Journals (Sweden)

    Juan M Vanegas

    Full Text Available The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, and identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10-13 kT per lipid to actuate the channel (by applying forces on protein-bound lipids and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin.

  18. 肿瘤干细胞理论的演变%Evolution of Cancer Stem Cell Paradigm

    Institute of Scientific and Technical Information of China (English)

    张雁

    2012-01-01

    肿瘤干细胞(CSC)是存存于肿瘤组织或肿瘤细胞群中具有干细胞特性的亚群.CSC具有自我更新和分化能力,可以分化为特性各异的细胞.CSC因其强大的起始肿瘤能力和抵抗治疗的特性而成为关注的焦点.肿瘤干细胞理论从起初的单向等级分化模式,发展到现在的随机和等级分化交互模式,较好地解释了肿瘤在形态和功能方面的多样性,是研究肿瘤的发生和发展的理想模型.本文通过对近年来在肿瘤干细胞研究领域的部分卓越成就的解析,阐述了肿瘤干细胞在分化模式、微环境调控和动态变化等方面的特性.%Cancer stem cells (CSC) are a subset of cancer cells that share the characteristics of self-renewal capacity and multipotency with stem cells. CSC produces daughter cells with differential nature and thus contributes to tumor. The presence of CSC is associated with tumor initiation and therapy-resistance. The hierarchical and stochastic CSC model can explain the phenotypic and functional heterogeneity in various types of cancer. In this paper, recent excellent observations in CSC, including cell-lineage, regulation of microenvironment and dynamic equilibrium between CSC and non-CSC are reviewed.

  19. Reimplementing the Mathematical Subject Classification (MSC) as a Linked Open Dataset

    CERN Document Server

    Lange, Christoph; Dimou, Anastasia; Bratsas, Charalampos; Corneli, Joseph; Sperber, Wolfram; Kohlhase, Michael; Antoniou, Ioannis

    2012-01-01

    The Mathematics Subject Classification (MSC) is a widely used scheme for classifying documents in mathematics by subject. Its traditional, idiosyncratic conceptualization and representation makes the scheme hard to maintain and requires custom implementations of search, query and annotation support. This limits uptake e.g. in semantic web technologies in general and the creation and exploration of connections between mathematics and related domains (e.g. science) in particular. This paper presents the new official implementation of the MSC2010 as a Linked Open Dataset, building on SKOS (Simple Knowledge Organization System). We provide a brief overview of the dataset's structure, its available implementations, and first applications.

  20. MSC POOL相邻池区切换自动均衡实现

    Institute of Scientific and Technical Information of China (English)

    陈鑫

    2014-01-01

    本文针对MSC POOL大规模组网部署后出现的相邻池区间跨POOL切换不均衡导致用户分布不均匀、话务不均衡问题,介绍了如何实现跨POOL切换的自动均衡、可控、可调,对MSC POOL多池区组网规划优化有一定参考应用价值。

  1. Supervising M.Sc. Students working in the 100 Gigabit Ethernet field using OPNET Modeler

    DEFF Research Database (Denmark)

    Ruepp, Sarah Renée; Berger, Michael Stübert; Wessing, Henrik

    2010-01-01

    This paper deals with supervision methods for M.Sc. students who are using OPNET Modeler for their thesis work within the field of 100 Gigabit Ethernet. We detail how we use OPNET Modeler in our M.Sc. projects at the Technical University of Denmark. In particular, we discuss on how we teach...... students to learn OPNET independently and in a short timeframe, and we outline what students find challenging and rewarding by using OPNET Modeler. Furthermore, we show some cases on how OPNET was applied in specific projects within the field of 100 Gigabit Ethernet....

  2. ANALYSIS WITH MSC ADAMS OF A 5-FINGER AND 3-PHALANX /FINGER UNDER-ACTUATEDMECHANICAL HAND

    Directory of Open Access Journals (Sweden)

    Gheorghe POPESCU

    2013-05-01

    Full Text Available This paper studies the analysis with MSC ADAMS of a 5-fingered and 3-phalanx/finger underactuatedmechanical hand, designed by the author to work on industrial robots. Moreover, in order to increasegrasping safety in the automated handling process, the author has fitted each finger with a locking sequence inthe final phase of grasping. Thus, the mechanism of mechanical hand is considered to be a mechanical systemand is treated like a set of rigid bodies connected by mechanical linkages and elastic elements. To model andsimulate this mechanism with MSC ADAMS programme, the author covered the following stages: constructionof the model, testing-simulation, validation, finishing, parameterization, and optimization

  3. Education of MSc and PhD Students in Fluid Power and Mechatronics at DTU

    DEFF Research Database (Denmark)

    Conrad, Finn

    1996-01-01

    The paper deals with education of MSc and PhD students in engineering areas fluid power and mechatronics at the Technical Univ of Denmark, DTU, Lyngby. The new education structure and programs for MSc and PhD students adapted to the change and development of technologies. Focus is on two of twenty...... engineering profilies:(1) Engineeing Design and Product Development and (2)Control Engineering which give possibilitie for specialisation in fluid power and mechatronics design and productdevelopment. Synthesis, design and self-learning competency have a high priority taking the importance of training...

  4. Post-thaw non-cultured and post-thaw cultured equine cord blood mesenchymal stromal cells equally suppress lymphocyte proliferation in vitro.

    Directory of Open Access Journals (Sweden)

    Lynn B Williams

    Full Text Available Multipotent mesenchymal stromal cells (MSC are receiving increased attention for their non-progenitor immunomodulatory potential. Cryopreservation is commonly used for long-term storage of MSC. Post-thaw MSC proliferation is associated with a lag-phase in vitro. How this lag-phase affect MSC immunomodulatory properties is unknown. We hypothesized that in vitro there is no difference in lymphocyte suppression potential between quick-thawed cryopreserved equine cord blood (CB MSC immediately included in mixed lymphocyte reaction (MLR and same MSC allowed post-thaw culture time prior to inclusion in MLR. Cryopreserved CB-MSC from five unrelated foals were compared using two-way MLR. For each of the five unrelated MSC cultures, paired MLR assays of MSC allowed five days of post-thaw culture and MSC included in MLR assay immediately post-thawing were evaluated. We report no difference in the suppression of lymphocyte proliferation by CB-MSC that had undergone post-thaw culture and MSC not cultured post-thaw (p<0.0001. Also, there was no inter-donor variability between the lymphocyte suppressive properties of MSC harvested from the five different donors (p = 0.13. These findings suggest that cryopreserved CB-MSC may have clinical utility immediately upon thawing. One implication hereof is the possibility of using cryopreserved CB-MSC at third party locations without the need for cell culture equipment or competencies.

  5. Parallel Programming Paradigms

    Science.gov (United States)

    1987-07-01

    GOVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER 4, TITL.: td Subtitle) S. TYPE OF REPORT & PERIOD COVERED Parallel Programming Paradigms...studied. 0A ITI is Jt, t’i- StCUI-eASSIICATION OFvrHIS PAGFrm".n Def. £ntered, Parallel Programming Paradigms Philip Arne Nelson Department of Computer...8416878 and by the Office of Naval Research Contracts No. N00014-86-K-0264 and No. N00014-85- K-0328. 8 ?~~ O .G 1 49 II Parallel Programming Paradigms

  6. Current view of mesenchymal stem cells biology (brief review

    Directory of Open Access Journals (Sweden)

    Maslova O. A.

    2012-06-01

    Full Text Available Although mesenchymal stem cells (MSC are in a focus of attention, some aspects of their biology are still unclear. This paper is a review of current research on MSC biology. The use of MSC in regenerative medicine is also briefly discussed.

  7. In situ tissue regeneration: chemoattractants for endogenous stem cell recruitment.

    Science.gov (United States)

    Vanden Berg-Foels, Wendy S

    2014-02-01

    Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration.

  8. Comparison of composite rotor blade models: A coupled-beam analysis and an MSC/NASTRAN finite-element model

    Science.gov (United States)

    Hodges, Robert V.; Nixon, Mark W.; Rehfield, Lawrence W.

    1987-01-01

    A methodology was developed for the structural analysis of composite rotor blades. This coupled-beam analysis is relatively simple to use compared with alternative analysis techniques. The beam analysis was developed for thin-wall single-cell rotor structures and includes the effects of elastic coupling. This paper demonstrates the effectiveness of the new composite-beam analysis method through comparison of its results with those of an established baseline analysis technique. The baseline analysis is an MSC/NASTRAN finite-element model built up from anisotropic shell elements. Deformations are compared for three linear static load cases of centrifugal force at design rotor speed, applied torque, and lift for an ideal rotor in hover. A D-spar designed to twist under axial loading is the subject of the analysis. Results indicate the coupled-beam analysis is well within engineering accuracy.

  9. Dynamics of self-directed learning in M.Sc. nursing students: A qualitative research

    Directory of Open Access Journals (Sweden)

    FATEMEH SHIRAZI

    2017-01-01

    Full Text Available Introduction: Working in the complex and ever changing healthcare settings forces the nurses and nursing students to be equipped with lifelong learning skills. One of the lifelong learning skills is self-directed learning. This study aimed to explore the M.Sc. nursing students’ self-directed learning activities. Methods: A qualitative design using conventional content analysis approach was used in this study. Semi-structured interviews were conducted with twelve Iranian M.Sc. nursing students who were selected using purposive sampling. Results: Data analysis indicated that the M.Sc. nursing students performed different activities in their self-directed learning. These activities were categorized into four main themes and ten subthemes. The main themes were “sensory perceptions”, “knowledge construction”, “problem-centered orientation”, and “interaction with others”. Conclusion: According to the findings, the M.Sc. nursing students performed different intellectual and experiential self-directed activities for promoting their learning. Besides, the students’ perseverance and inquisitiveness played an important role in their self-directed learning in the challenging clinical environments.

  10. Competencies of BSc and MSc programmes in electrical engineering and student portfolios

    NARCIS (Netherlands)

    Mouthaan, Ton J.; Brink, R.W.; Vos, H.

    2002-01-01

    General goals of a BSc and MSc in electrical engineering are formulated, leading to a 'mission' statement clarifying the rationale behind the programmes in relation to the needs of society. These goals are made operational in terms of competencies that engineers educated through our programmes are r

  11. Studies on sensitivity to tension and gating pathway of MscL by molecular dynamic simulation

    Institute of Scientific and Technical Information of China (English)

    Jun-Yu Xie; Guang-Hong Ding

    2013-01-01

    Mechanosensitive (MS) ion channels play an important role in various physiological processes.Although the determination of the structure of mechanosensitive channel of large conductance (MscL) makes the simulation study possible,it has not so far been possible to directly simulate the gating mechanism of MscL in atomic detail.In this article,MscL has been studied via molecular dynamic (MD)simulations to gain a detailed description of the sensitivity to lateral tension and the gating pathway.MscL undergoes conformational rearrangement in sustaining lateral tension,and the open state is obtained when 2.0 MPa lateral tension is directly applied on the pure protein.During the opening process,Loop region responds to tension first,and the mechanical sensitivity is followed by S1 domain.Transmembrane (TM) bundle is the key position for channel opening,and the motion of TM1 helices finally realizes the significant expansion of the constricted gating pore.C-terminus domain presents expansion later during the TM opening.In our study,return of the whole protein to the initial closed state is achieved only in the early opening stage.During the relaxation from the open state,the TM helices are the most mobile domain,which is different from the opening process.

  12. New MSc programme in Sustainable Energy at Risø DTU

    DEFF Research Database (Denmark)

    Ryde, M.

    2007-01-01

    In September 2008, the fi rst batch of students will start a new MSc programme which is based at Risø DTU. It is a two-year study programme, so the students will be well into their studies when the UN’s climate conference is held in Copenhagen in 2009...

  13. Dynamics of self-directed learning in M.Sc. nursing students: A qualitative research

    Science.gov (United States)

    SHIRAZI, FATEMEH; SHARIF, FARKHONDEH; MOLAZEM, ZAHRA; ALBORZI, MAHBOOBEH

    2017-01-01

    Introduction: Working in the complex and ever changing healthcare settings forces the nurses and nursing students to be equipped with lifelong learning skills. One of the lifelong learning skills is self-directed learning. This study aimed to explore the M.Sc. nursing students’ self-directed learning activities. Methods: A qualitative design using conventional content analysis approach was used in this study. Semi-structured interviews were conducted with twelve Iranian M.Sc. nursing students who were selected using purposive sampling. Results: Data analysis indicated that the M.Sc. nursing students performed different activities in their self-directed learning. These activities were categorized into four main themes and ten subthemes. The main themes were “sensory perceptions”, “knowledge construction”, “problem-centered orientation”, and “interaction with others”. Conclusion: According to the findings, the M.Sc. nursing students performed different intellectual and experiential self-directed activities for promoting their learning. Besides, the students’ perseverance and inquisitiveness played an important role in their self-directed learning in the challenging clinical environments. PMID:28124019

  14. Erythropoietin Modification Enhances the Protection of Mesenchymal Stem Cells on Diabetic Rat-Derived Schwann Cells: Implications for Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Shuyun Zhang

    2017-01-01

    Full Text Available Diabetes-triggered apoptosis of Schwann cells (SC contributes to the degradation of diabetic peripheral neuropathy (DNP. In recent years, mesenchymal stem cells (MSC were applied to DPN repair and it was demonstrated that paracrine secretion played a key role in neuroprotection exerted by MSC. Erythropoietin (EPO is a potent cytokine capable of reducing apoptosis of SC. However, the expression of EPO in MSC is limited. In this study, we hypothesized that overexpression of EPO in MSC (EPO-MSC may significantly improve their neuroprotective potentials. The EPO overexpression in MSC was achieved by lentivirus transduction. SC derived from the periphery nerve of diabetic rats were cocultured with MSC or EPO-MSC in normal or high glucose culture condition, respectively. In normal glucose culture condition, the overexpression of EPO in MSC promoted the MSC-induced restoration of SC from diabetic rats, including increases in GSH level and cell viability, decrease in TUNEL apoptosis, upregulation of antiapoptotic proteins, p-Akt, and Bcl-2, and downregulation of proapoptotic proteins, cleaved caspase-3, and Bax. The subsequent results in high glucose culture condition showed similar promotions achieved by EPO-MSC. Thus, it could be concluded that EPO-MSC possessed a potent potential in hampering apoptosis of SC, and the suppression was probably attributed to attenuating oxidative stress and regulating apoptosis related protein factors.

  15. Erythropoietin Modification Enhances the Protection of Mesenchymal Stem Cells on Diabetic Rat-Derived Schwann Cells: Implications for Diabetic Neuropathy

    Science.gov (United States)

    Zhang, Shuyun

    2017-01-01

    Diabetes-triggered apoptosis of Schwann cells (SC) contributes to the degradation of diabetic peripheral neuropathy (DNP). In recent years, mesenchymal stem cells (MSC) were applied to DPN repair and it was demonstrated that paracrine secretion played a key role in neuroprotection exerted by MSC. Erythropoietin (EPO) is a potent cytokine capable of reducing apoptosis of SC. However, the expression of EPO in MSC is limited. In this study, we hypothesized that overexpression of EPO in MSC (EPO-MSC) may significantly improve their neuroprotective potentials. The EPO overexpression in MSC was achieved by lentivirus transduction. SC derived from the periphery nerve of diabetic rats were cocultured with MSC or EPO-MSC in normal or high glucose culture condition, respectively. In normal glucose culture condition, the overexpression of EPO in MSC promoted the MSC-induced restoration of SC from diabetic rats, including increases in GSH level and cell viability, decrease in TUNEL apoptosis, upregulation of antiapoptotic proteins, p-Akt, and Bcl-2, and downregulation of proapoptotic proteins, cleaved caspase-3, and Bax. The subsequent results in high glucose culture condition showed similar promotions achieved by EPO-MSC. Thus, it could be concluded that EPO-MSC possessed a potent potential in hampering apoptosis of SC, and the suppression was probably attributed to attenuating oxidative stress and regulating apoptosis related protein factors.

  16. Photo-irradiation paradigm: Mapping a remarkable facile technique used for advanced drug, gene and cell delivery.

    Science.gov (United States)

    Shaker, Mohamed A; Younes, Husam M

    2015-11-10

    Undoubtedly, the progression of photo-irradiation technique has provided a smart engineering tool for the state-of-the-art biomaterials that guide the biomedical and therapeutic domains for promoting the modern pharmaceutical industry. Many investigators had exploited such a potential technique to create/ameliorate numerous pharmaceutical carriers. These carriers show promising applications that vary from small drug to therapeutic protein delivery and from gene to living cell encapsulation design. Harmony between the properties of precisely engineered precursors and the formed network structure broadens the investigator's intellect for both brilliant creations and effective applications. As well, controlling photo-curing at the formulation level, through manipulating the absorption of light stimuli, photoinitiator system and photo-responsive precursor, facilitates the exploration of novel distinctive biomaterials. Discussion of utilizing different photo-curing procedures in designing/formulation of different pharmaceutical carriers is the main emphasis of this review. In addition, recent applications of these intelligent techniques in targeted, controlled, and sustained drug delivery with understanding of photo-irradiation concept and mechanism are illustrated.

  17. Characterization of Human Mesenchymal Stem Cells from Ewing Sarcoma Patients. Pathogenetic Implications

    Science.gov (United States)

    Amaral, Ana Teresa; Manara, Maria Cristina; Berghuis, Dagmar; Ordóñez, José Luis; Biscuola, Michele; Lopez-García, Maria Angeles; Osuna, Daniel; Lucarelli, Enrico; Alviano, Francesco; Lankester, Arjan; Scotlandi, Katia; de Álava, Enrique

    2014-01-01

    Background Ewing Sarcoma (EWS) is a mesenchymal-derived tumor that generally arises in bone and soft tissue. Intensive research regarding the pathogenesis of EWS has been insufficient to pinpoint the early events of Ewing sarcomagenesis. However, the Mesenchymal Stem Cell (MSC) is currently accepted as the most probable cell of origin. Materials and Methods In an initial study regarding a deep characterization of MSC obtained specifically from EWS patients (MSC-P), we compared them with MSC derived from healthy donors (MSC-HD) and EWS cell lines. We evaluated the presence of the EWS-FLI1 gene fusion and EWSR1 gene rearrangements in MSC-P. The presence of the EWS transcript was confirmed by q-RT-PCR. In order to determine early events possibly involved in malignant transformation, we used a multiparameter quantitative strategy that included both MSC immunophenotypic negative/positive markers, and EWS intrinsic phenotypical features. Markers CD105, CD90, CD34 and CD45 were confirmed in EWS samples. Results We determined that MSC-P lack the most prevalent gene fusion, EWSR1-FLI1 as well as EWSR1 gene rearrangements. Our study also revealed that MSC-P are more alike to MSC-HD than to EWS cells. Nonetheless, we also observed that EWS cells had a few overlapping features with MSC. As a relevant example, also MSC showed CD99 expression, hallmark of EWS diagnosis. However, we observed that, in contrast to EWS cells, MSC were not sensitive to the inhibition of CD99. Conclusions In conclusion, our results suggest that MSC from EWS patients behave like MSC-HD and are phenotypically different from EWS cells, thus raising important questions regarding MSC role in sarcomagenesis. PMID:24498265

  18. European MSc Programs in Nuclear Sciences—To meet the Need of Stakeholders

    Science.gov (United States)

    Salbu, Brit; Skipperud, Lindis; Priest, Nick; Garelick, Hemda; Tamponnet, Christian; Mitchell, Peter

    2009-08-01

    A stakeholder needs assessment, carried out under the EU-EURAC and EU-ENEN II projects, clearly showed that, at the European level, there are a significant and constant need for post-graduates with skills in radiochemistry, radioecology, radiation dosimetry and environmental modelling and a smaller, but still important, demand for radiobiologists and bio-modellers. Most of these needs are from government organizations. If only the nuclear industry is considered, then the largest demand is for radiochemists and radiation protection dosimetrists. Given this spectrum of need and existing capacity in the areas of radiobiology it was concluded that the needs identified would be most efficiently met by three new degree programs: • European MSc Radiation Protection • European MSc Analytical Radiochemistry • European MSc Radioecology. All three master programs would be developed using the framework provided by the Bologna Convention and the lecturing could be shared among specialist Scientists within a network of collaborating universities. Therefore, educational plans have been developed for the above MSc degrees. These plans envisage each degree comprising three modules that are common to all the degrees (3×10 ECTS credits), three specialist modules (3×10 ECTS credits) and a research project (1×60 ECTS credits). The courses should be aimed, not only to fill the identified European postgraduate education gap in radiological sciences, but also to provide a modular structure that is easily accessed by stakeholders for CPD training. It is anticipated that the European Masters will meet the academic training requirements of qualified experts", as defined by the European Commission and the IAEA. At the Norwegian University of Life Sciences (UMB) a pilot MSc in Radioecology has successfully been initiated in collaboration with UK and France.

  19. Strength Evaluation System for Aircraft Panel Structures Based on MSC.Patran%基于MSC.Patran的飞机壁板结构强度校核系统

    Institute of Scientific and Technical Information of China (English)

    汤超; 乔玉炜

    2012-01-01

    After getting the result from FEA in the aircraft panel structure model, one should add the engineering calculate method into this result to get the final strength evaluation for this panel structures. To implement the strength evaluation system for aircraft panel structures by modularization method, a program based on commercial software MSC. Patran is developed by using PCL language provided by MSC. Patran and journal file. The program is accomplished with start-up file, user self-defined menu and graphical interface, automatically running the analysis and reading results methods. Several typical cases are analyzed by the program and the results showed that the program can not only meet the variety requirement of aircraft panel structure evaluation, but also improve the efficiencies.%在得到飞机璧板结构的有限元分析结果之后,需要利用工程方法对此计算结果进行评估,最终得到壁板结构的强度评估结果.以有限元软件MSC.Patran为平台,利用其二次开发语言PCL( PATRAN Command Language),通过自动加载编译函数文件、用户自定义菜单和图形界面和读取结果等技术,开发了飞机壁板结构强度校核系统.使用此系统对某些典型的壁板结构案例进行了分析,结果表明该程序不仅能够满足较大范围内的各种飞机壁板结构的强度校核要求,而且还可以大大提高飞机设计者的工作效率.

  20. Simulation of Air Suspension and Full-vehicle with MSC Adams/Car%基于MSC Adams/Car的空气悬架及整车仿真

    Institute of Scientific and Technical Information of China (English)

    王登峰; 郎锡泽; 马天飞

    2006-01-01

    利用MSC Adams/Car软件建立载货汽车后空气悬架系统多体动力学模型,仿真计算了悬架垂直刚度特性,证明模型的正确性. 建立Adams/Car的整车模型,进行稳态回转试验的仿真分析. 将仿真结果与道路试验结果进行比较,验证虚拟样机模型的正确性.

  1. Winnicott's paradigm outlined

    Directory of Open Access Journals (Sweden)

    Zeljko Loparic

    Full Text Available The main objective of this paper is to present a unified view of Winnicott’s contribution to psychoanalysis. Part I (Sections 1-4 starts off by recalling that, according to some important commentators, Winnicott introduced a change in paradigms in psychoanalysis. In order to show that this change can be viewed as an overall “switch in paradigms”, in the sense given by T. S. Kuhn, this paper presents an account of the Kuhn’s view of science and offers a reconstruction of Freud’s Oedipal, Triangular or “Toddler-in-the-Mother’s-Bed” Paradigm. Part II (Sections 5-13 shows that as early as the 1920’s Winnicott encountered insurmountable anomalies in the Oedipal paradigm and, for that reason, started what can be called revolutionary research for a new framework of psychoanalysis. This research led Winnicott, especially during the last period of his life, to produce an alternative dual or “Baby-on-the-Mother’s-Lap” Paradigm. This new paradigm is described in some detail, especially the paradigmatic dual mother-baby relation and Winnicott’s dominant theory of maturation. Final remarks are made regarding Winnicott’s heritage and the future of psychoanalysis.

  2. Three paradigms of horror

    Directory of Open Access Journals (Sweden)

    Dejan Ognjanović

    2016-07-01

    Full Text Available Starting with the definition of horror as a literary genre the core story of which is based on a meeting with threatening Otherness whose influx into consensual reality and it’s tacit normality creates unrest and awakens fear in the protagonists and the audience, this paper defines the three key paradigms of the horror genre, based on the causes of fear, or rather the “monstrous” Otherness in them. Paradigm 1 concerns the “fear of one’s own self”: the root of the fear is inside, in the individual psyche, in the split, deceived, or in some other way unreliable self which is, consciously or unconsciously, harmful to others, and ultimately to itself. Paradigm 2 deals with the “Fear of others”: the root of fear is outside and is concerned with other people and other creatures which have an urge to occupy a certain human microcosm. Paradigm 3 is concerned with the “Fear of the numinous”: the root of the fear is mostly situated on the outside; however its shape is amorphous, ambivalent and unknowable. The “monster” is faceless; it touches on primary forces of the divine/demonic, and as such is situated on the very border between inside/outside. All three paradigms, with their main approaches and constitutive elements, are modulated through two basic possible treatments: the conservative and the progressive (liberal, which affords a total of six basic variations of horror. Starting from definitions given by John Carpenter, Robin Wood and his own, the author analyzes representative examples from horror literature and film for each paradigm and its variation, with a special accent on the image of Otherness and its connection to the norm, its intrusion into the status quo, anthropocentrism and the presence or absence of a happy ending. The paper demonstrates the richness of connotative potential within the horror genre and provides a basis for its taxonomy.

  3. Mesenchymal stem cells directly interact with breast cancer cells and promote tumor cell growth in vitro and in vivo.

    Science.gov (United States)

    Mandel, Katharina; Yang, Yuanyuan; Schambach, Axel; Glage, Silke; Otte, Anna; Hass, Ralf

    2013-12-01

    Cellular interactions were investigated between human mesenchymal stem cells (MSC) and human breast cancer cells. Co-culture of the two cell populations was associated with an MSC-mediated growth stimulation of MDA-MB-231 breast cancer cells. A continuous expansion of tumor cell colonies was progressively surrounded by MSC(GFP) displaying elongated cell bodies. Moreover, some MSC(GFP) and MDA-MB-231(cherry) cells spontaneously generated hybrid/chimeric cell populations, demonstrating a dual (green fluorescent protein+cherry) fluorescence. During a co-culture of 5-6 days, MSC also induced expression of the GPI-anchored CD90 molecule in breast cancer cells, which could not be observed in a transwell assay, suggesting the requirement of direct cellular interactions. Indeed, MSC-mediated CD90 induction in the breast cancer cells could be partially blocked by a gap junction inhibitor and by inhibition of the notch signaling pathway, respectively. Similar findings were observed in vivo by which a subcutaneous injection of a co-culture of primary MSC with MDA-MB-231(GFP) cells into NOD/scid mice exhibited an about 10-fold increased tumor size and enhanced metastatic capacity as compared with the MDA-MB-231(GFP) mono-culture. Flow cytometric evaluation of the co-culture tumors revealed more than 90% of breast cancer cells with about 3% of CD90-positive cells, also suggesting an MSC-mediated in vivo induction of CD90 in MDA-MB-231 cells. Furthermore, immunohistochemical analysis demonstrated an elevated neovascularization and viability in the MSC/MDA-MB-231(GFP)-derived tumors. Together, these data suggested an MSC-mediated growth stimulation of breast cancer cells in vitro and in vivo by which the altered MSC morphology and the appearance of hybrid/chimeric cells and breast cancer-expressing CD90(+) cells indicate mutual cellular alterations.

  4. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion

    Directory of Open Access Journals (Sweden)

    Elke eEggenhofer

    2012-09-01

    Full Text Available Mesenchymal stem cells (MSC are under investigation as a therapy for a variety of disorders. Although animal models show long term regenerative and immunomodulatory effects of MSC, the fate of MSC after infusion remains to be elucidated. In the present study the localization and viability of MSC was examined by isolation and re-culture of intravenously infused MSC. C57BL/6 MSC (500,000 constitutively expressing DsRed-fluorescent protein and radioactively labeled with Cr-51 were infused via the tail vein in wild type C57BL/6 mice. After 5min, 1h, 24h or 72h, mice were sacrificed and blood, lungs, liver, spleen, kidneys and bone marrow removed. One hour after MSC infusion the majority of Cr-51 was found in the lungs, whereas after 24h Cr-51 was mainly found in the liver. Tissue cultures demonstrated that viable donor MSC were present in the lungs up to 24h after infusion, after which they disappeared. No viable MSC were found in the other organs examined at any time. The induction of ischemia-reperfusion injury in the liver did not trigger the migration of viable MSC to the liver. These results demonstrate that MSC are short-lived after i.v. infusion and that viable MSC do not pass the lungs. Cell debris may be transported to the liver. Long term immunomodulatory and regenerative effects of infused MSC must therefore be mediated via other cell types.

  5. Nuclear receptors Nur77 and Nurr1 modulate mesenchymal stromal cell migration

    NARCIS (Netherlands)

    Maijenburg, M.W.; Gilissen, C.; Melief, S.M.; Kleijer, M.; Weijer, K.; Ten Brinke, A.; Roelofs, H.; Tiel, C.M. van; Veltman, J.A.; Vries, C.J. de; Schoot, C.E. van der; Voermans, C.

    2012-01-01

    Detailed understanding of mesenchymal stromal cells (MSC) migration is imperative for future cellular therapies. To identify genes involved in the process of MSC migration, we generated gene expression profiles of migrating and nonmigrating fetal bone marrow MSC (FBMSC). Only 12 genes showed differe

  6. The Application of MSC Pool Technology in Soft Switch Equipment Disaster Recovery%MSC Pool技术在软交换设备容灾中的应用

    Institute of Scientific and Technical Information of China (English)

    刘扬

    2008-01-01

    重点对MSC Pool技术进行了介绍,并对该技术应用在软交换设备容灾时的优势和可能出现的问题进行了分析,提出了在现网中软交换设备采用MSC Pool组网问题的解决思路并对MSC Pool方式组网建设的应用前景进行了展望.

  7. Alternative Evaluation Research Paradigm.

    Science.gov (United States)

    Patton, Michael Quinn

    This monograph is one of a continuing series initiated to provide materials for teachers, parents, school administrators, and governmental decision-makers that might encourage reexamination of a range of evaluation issues and perspectives about schools and schooling. This monograph is a description and analysis of two contrasting paradigms: one…

  8. Antagonism of the Met5-enkephalin-opioid growth factor receptor-signaling axis promotes MSC to differentiate into osteoblasts.

    Science.gov (United States)

    Thakur, Nikhil A; DeBoyace, Sean D; Margulies, Bryan S

    2016-07-01

    Chronic opioid therapy is associated with bone loss. This led us to hypothesize that the opioid antagonists, that include naloxone, would stimulate bone formation by regulating MSC differentiation. The opioid growth factor receptor (OGFR) is a non-canonical opioid receptor that binds naloxone with high affinity whereas the native opioid growth factor, met5-enkephalin (met5), binds both the OGFR and the canonical delta opioid receptor (OPRD). Naloxone and an shRNA OGFR lentivirus were employed to disrupt the OGFR-signaling axis in cultured MSC. In parallel, naloxone was administered to bone marrow using a mouse unicortical defect model. OPRD, OGFR, and the met5-ligand were highly expressed in MSC and osteoblasts. A pulse-dose of naloxone increased mineral formation in MSC cultures in contrast to MSC treated with continuous naloxone or OGFR deficient MSC. Importantly, SMAD1 and SMAD8/9 expression increased after a pulse dose of naloxone whereas SMAD1, SMAD7, and ID1 were increased in the OGFR deficient MSC. Inhibited OGFR signaling decreased proliferation and increased p21 expression. The addition of naloxone to the unicortical defect resulted in increased bone formation within the defect. Our data suggest that novel mechanism through which signaling through the OGFR regulates osteogenesis via negative regulation of SMAD1 and p21. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1195-1205, 2016.

  9. Advanced finite element simulation with MSC Marc application of user subroutines

    CERN Document Server

    Javanbakht, Zia

    2017-01-01

    This book offers an in-depth insight into the general-purpose finite element program MSC Marc, which is distributed by MSC Software Corporation. It is a specialized program for nonlinear problems (implicit solver) which is common in academia and industry. The primary goal of this book is to provide a comprehensive introduction to a special feature of this software: the user can write user-subroutines in the programming language Fortran, which is the language of all classical finite element packages. This subroutine feature allows the user to replace certain modules of the core code and to implement new features such as constitutive laws or new elements. Thus, the functionality of commercial codes (‘black box’) can easily be extended by linking user written code to the main core of the program. This feature allows to take advantage of a commercial software package with the flexibility of a ‘semi-open’ code. .

  10. The finite element analysis program MSC Marc/Mentat a first introduction

    CERN Document Server

    Öchsner, Andreas

    2016-01-01

    Based on simple examples, this book offers a short introduction to the general-purpose finite element program MSC Marc, a specialized program for non-linear problems (implicit solver) distributed by the MSC Software Corporation, which is commonly used in academia and industry. Today the documentation of all finite element programs includes a variety of step-by-step examples of differing complexity, and in addition, all software companies offer professional workshops on different topics. As such, rather than competing with these, the book focuses on providing simple examples, often single-element problems, which can easily be related to the theory that is discussed in finite element lectures. This makes it an ideal companion book to classical introductory courses on the finite element method.

  11. MSc Dissertation

    DEFF Research Database (Denmark)

    Roued-Cunliffe, Henriette

    2008-01-01

    Heritage Portals are in this dissertation defined as deep portals which can give access to external resource contents. This dissertation has developed such a portal which accesses the Swedish SMR, FMIS and the ARK system developed by L – P : Archaeology through web services. The development...... of the web Service for the ARK system was done as a part of this project combined with the creating of a WFS web-mapping service serving the spatial part of the dataset collected as a part of the Sintana project. The textual part of this dataset has been incorporated into an ARK system in the same way...... that the Portus project dataset was. Both these projects are available through the ARK web service. The portal accessed the FMIS and ARK web service and re-maps the XML output to Midas standard formatted XML and combined them. This allows the portal to do a cross-search of the two datasets and return the data...

  12. Allo-reactivity of mesenchymal stem cells in rhesus macaques is dose and haplotype dependent and limits durable cell engraftment in vivo.

    Directory of Open Access Journals (Sweden)

    Iryna A Isakova

    Full Text Available The emerging paradigm that MSCs are immune privileged has fostered the use of "off-the-shelf" allogeneic MSC-based therapies in human clinical trials. However, this approach ignores studies in experimental animals wherein transplantation of MSCs across MHC boundaries elicits measurable allo-immune responses. To determine if MSCs are hypo-immunogeneic, we characterized the immune response in rhesus macaques following intracranial administration of allogeneic vs. autologous MSCs. This analysis revealed unambiguous evidence of productive allo-recognition based on expansion of NK, B and T cell subsets in peripheral blood and detection of allo-specific antibodies in animals administered allogeneic but not autologous MSCs. Moreover, the degree of MHC class I and II mismatch between the MSC donor and recipient significantly influenced the magnitude and nature of the allo-immune response. Consistent with these findings, real-time PCR analysis of brain tissue from female recipients administered varying doses of male, allogeneic MSCs revealed a significant inverse correlation between MSC engraftment levels and cell dose. Changes in post-transplant neutrophil and lymphocyte counts also correlated with dose and were predictive of overall MSC engraftment levels. However, secondary antigen challenge failed to elicit a measurable immune response in allogeneic recipients. Finally, extensive behavior testing of animals revealed no main effect of cell dose on motor skills, social development, or temperament. Collectively, these data indicate that allogeneic MSCs are weakly immunogenic when transplanted across MHC boundaries in rhesus macaques and this negatively impacts durable engraftment levels. Therefore the use of unrelated donor MSCs should be carefully evaluated in human patients.

  13. 探讨MSC Pool技术在移动软交换网络的研究和应用

    Institute of Scientific and Technical Information of China (English)

    丁中华

    2014-01-01

    MSC Pool技术在移动软交换网络中起到了十分重要的作用,本文对MSC Pool技术的概念和工作原理做了介绍,并分析了MSC Pool技术的要点,以及组建MSC Pool的前提条件。

  14. Hypoxic culture conditions for Mesenchymal Stromal/Stem Cells from Wharton's jelly: a critical parameter to consider in a therapeutic context.

    Science.gov (United States)

    Reppel, Loic; Margossian, Talar; Yaghi, Layale; Moreau, Philippe; Mercier, Nathalie; Leger, Leonore; Hupont, Sebastien; Stoltz, Jean-Francois; Bensoussan, Daniele; Huselstein, Celine

    2014-01-01

    Mesenchymal Stromal/Stem Cells from human Wharton's jelly (WJ-MSC) are an abundant and interesting source of stem cells for applications in cell and tissue engineering. Their fetal origin confers specific characteristics compared to Mesenchymal Stromal/Stem Cells isolated from human bone marrow (BM-MSC). The aim of this work was to optimize WJ-MSC culture conditions for their subsequent clinical use. We focused on the influence of oxygen concentration during monolayer expansion on several parameters to characterize MSC. Our work distinguished WJ-MSC from BM-MSC in terms of proliferation, telomerase activity and adipogenic differentiation. We also showed that hypoxia had a beneficial effect on proliferation potential, clonogenic capacity and to a lesser extent, on HLA-G expression of WJ-MSC during their expansion. Moreover, we reported for the first time an increase in chondrogenic differentiation when WJ-MSC were expanded under hypoxia. In an allogeneic therapeutic context, production of clinical batches requires generating high numbers of MSC whilst maintaining the cells' properties. Considering our results, hypoxia will be an important parameter to take into account. In addition, the clinical use of WJ-MSC would provide significant numbers of cells with maintenance of their proliferation and differentiation potential, particularly their chondrogenic potential. Due to their chondrogenic differentiation potential, WJ-MSC promise to be an interesting source of MSC for cell therapy or tissue engineering for cartilage repair and/or regeneration.

  15. Application Progress of MSC-stents Complex in Bone Repair%间充质干细胞-支架复合体运用于骨修复的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘印

    2013-01-01

    Bone defect is a common complication after fracture, and how to effectively repair it is the hot topic in the current medical study. The clinical application of bone tissue engineering technology is gradually rising,and MSC-stents complex can effectively combine their advantages,which is beneficial to the treatment of bone defect. Here is to summarize the MSC-stents requirements, such as cell number, microenvironment simulation and related growth factor function etc. ,to provide a reference basis for further studies.%骨缺损是骨折后的常见并发症,如何有效地进行骨修复是当前医学研究的热点.骨组织工程技术在临床上应用逐渐兴起,间充质干细胞(MSC)-支架复合体可有效结合干细胞与支架的骨修复优势,利于骨缺损的治疗.该文总结分析有关MSC-支架复合体条件需求,如细胞数量,微环境模拟,相关生长因子作用等,为今后的深入研究提供参考.

  16. Research on MSC Pool Tecnology and the Solution of Called Recovery for Huawei Enterprise%MSC Pool技术与华为被叫恢复方案

    Institute of Scientific and Technical Information of China (English)

    马欢

    2010-01-01

    MSC Pool是3G核心网建设中最受关注的技术之一,其理论优势在移动现网中有充分表现.使用该技术可满足网络容灾的需要,解决移动网络中的"潮汐效应",减少局间切换及局问位置更新.华为被叫快速恢复方案采用SCCP信令点负荷分担方式实现对PRN信令的备份处理,可用于解决MSC容灾故障.

  17. MSC POOL Technology Risk Analysis of Migration Patterns of Different Users%MSC POOL技术中不同用户迁移方式风险分析

    Institute of Scientific and Technical Information of China (English)

    陈巍

    2011-01-01

    该文介绍了MSC POOL的解决方案与技术优势,然后针对MSC POOL中用户迁移的两种方案做了重点阐述,并对不同方案进行风险分析,分析出对不同组网方式下对现网用户的影响.

  18. Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation.

    Science.gov (United States)

    Yang, Zijiang; Concannon, John; Ng, Kelvin S; Seyb, Kathleen; Mortensen, Luke J; Ranganath, Sudhir; Gu, Fangqi; Levy, Oren; Tong, Zhixiang; Martyn, Keir; Zhao, Weian; Lin, Charles P; Glicksman, Marcie A; Karp, Jeffrey M

    2016-07-26

    Pre-treatment or priming of mesenchymal stem cells (MSC) prior to transplantation can significantly augment the immunosuppressive effect of MSC-based therapies. In this study, we screened a library of 1402 FDA-approved bioactive compounds to prime MSC. We identified tetrandrine as a potential hit that activates the secretion of prostaglandin E2 (PGE2), a potent immunosuppressive agent, by MSC. Tetrandrine increased MSC PGE2 secretion through the NF-κB/COX-2 signaling pathway. When co-cultured with mouse macrophages (RAW264.7), tetrandrine-primed MSC attenuated the level of TNF-α secreted by RAW264.7. Furthermore, systemic transplantation of primed MSC into a mouse ear skin inflammation model significantly reduced the level of TNF-α in the inflamed ear, compared to unprimed cells. Screening of small molecules to pre-condition cells prior to transplantation represents a promising strategy to boost the therapeutic potential of cell therapy.

  19. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion

    NARCIS (Netherlands)

    E. Eggenhofer (Elke); V. Benseler (Volker); H.K. Kroemer (Heyo); F. Popp (Felix); E.K. Geissler (Edward); H.J. Schlitt (Hans); C.C. Baan (Carla); M.H. Dahlke (Marc); M.J. Hoogduijn (Martin)

    2012-01-01

    textabstractMesenchymal stem cells (MSC) are under investigation as a therapy for a variety of disorders. Although animal models show long term regenerative and immunomodulatory effects of MSC, the fate of MSC after infusion remains to be elucidated. In the present study the localization and viabili

  20. Inactivated Mesenchymal Stem Cells Maintain Immunomodulatory Capacity

    NARCIS (Netherlands)

    Luk, Franka; de Witte, Samantha F. H.; Korevaar, Sander S.; Roemeling, Marieke; Franquesa, Marcella; Strini, Tanja; van den Engel, Sandra; Gargesha, Madhusudhana; Roy, Debashish; Dor, Frank J. M. F.; Horwitz, Edwin M.; de Bruin, Ron W. F.; Betjes, Michiel G. H.; Baan, Carla C.; Hoogduijn, Martin J.

    2016-01-01

    Mesenchymal stem cells (MSC) are studied as a cell therapeutic agent for treatment of various immune diseases. However, therapy with living culture-expanded cells comes with safety concerns. Furthermore, development of effective MSC immunotherapy is hampered by lack of knowledge of the mechanisms of

  1. Composite scaffolds for osteochondral repair obtained by combination of additive manufacturing, leaching processes and hMSC-CM functionalization.

    Science.gov (United States)

    Díaz Lantada, Andrés; Alarcón Iniesta, Hernán; García-Ruíz, Josefa Predestinación

    2016-02-01

    Articular repair is a relevant and challenging area for the emerging fields of tissue engineering and biofabrication. The need of significant gradients of properties, for the promotion of osteochondral repair, has led to the development of several families of composite biomaterials and scaffolds, using different effective approaches, although a perfect solution has not yet been found. In this study we present the design, modeling, rapid manufacturing and in vitro testing of a composite scaffold aimed at osteochondral repair. The presented composite scaffold stands out for having a functional gradient of density and stiffness in the bony phase, obtained in titanium by means of computer-aided design combined with additive manufacture using selective laser sintering. The chondral phase is obtained by sugar leaching, using a PDMS matrix and sugar as porogen, and is joined to the bony phase during the polymerization of PDMS, therefore avoiding the use of supporting adhesives or additional intermediate layers. The mechanical performance of the construct is biomimetic and the stiffness values of the bony and chondral phases can be tuned to the desired applications, by means of controlled modifications of different parameters. A human mesenchymal stem cell (h-MSC) conditioned medium (CM) is used for improving scaffold response. Cell culture results provide relevant information regarding the viability of the composite scaffolds used.

  2. Applications of Recombinant DNA Technology in Gastrointestinal Medicine and Hepatology: Basic Paradigms of Molecular Cell Biology. Part C: Protein Synthesis and Post-Translational Processing in Eukaryotic Cells

    Directory of Open Access Journals (Sweden)

    Gary E Wild

    2000-01-01

    Full Text Available The translation of mRNA constitutes the first step in the synthesis of a functional protein. The polypeptide chain is subsequently folded into the appropriate three-dimensional configuration and undergoes a variety of processing steps before being converted into its active form. These processing steps are intimately related to the cellular events that occur in the endoplasmic reticulum and Golgi compartments, and determine the sorting and transport of different proteins to their appropriate destinations within the cell. While the regulation of gene expression occurs primarily at the level of transcription, the expression of many genes can also be controlled at the level of translation. Most proteins can be regulated in response to extracellular signals. In addition, intracellular protein levels can be controlled by differential rates of protein degradation. Thus, the regulation of both the amounts and activities of intracellular proteins ultimately determines all aspects of cell behaviour.

  3. Perivascular cells for regenerative medicine

    NARCIS (Netherlands)

    M. Crisan (Mihaela); M. Corselli (Mirko); W.C. Chen (William); B. Péault (Bruno)

    2012-01-01

    textabstractMesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We an

  4. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demuth, Christina; Safwat, Akmal;

    2016-01-01

    ) treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI...... growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8...

  5. HCELL Expression on Murine MSC Licenses Pancreatotropism and Confers Durable Reversal of Autoimmune Diabetes in NOD Mice.

    Science.gov (United States)

    Abdi, Reza; Moore, Robert; Sakai, Shinobu; Donnelly, Conor B; Mounayar, Marwan; Sackstein, Robert

    2015-05-01

    Type 1 diabetes (T1D) is an immune-mediated disease resulting in destruction of insulin-producing pancreatic beta cells. Mesenchymal stem cells (MSCs) possess potent immunomodulatory properties, garnering increasing attention as cellular therapy for T1D and other immunologic diseases. However, MSCs generally lack homing molecules, hindering their colonization at inflammatory sites following intravenous (IV) administration. Here, we analyzed whether enforced E-selectin ligand expression on murine MSCs could impact their effect in reversing hyperglycemia in nonobese diabetic (NOD) mice. Although murine MSCs natively do not express the E-selectin-binding determinant sialyl Lewis(x) (sLe(x) ), we found that fucosyltransferase-mediated α(1,3)-exofucosylation of murine MSCs resulted in sLe(x) display uniquely on cell surface CD44 thereby creating hematopoietic cell E-/L-selectin ligand (HCELL), the E-selectin-binding glycoform of CD44. Following IV infusion into diabetic NOD mice, allogeneic HCELL(+) MSCs showed threefold greater peri-islet infiltrates compared to buffer-treated (i.e., HCELL(-) ) MSCs, with distribution in proximity to E-selectin-expressing microvessels. Exofucosylation had no effect on MSC immunosuppressive capacity in in vitro assays; however, although engraftment was temporary for both HCELL(+) and HCELL(-) MSCs, administration of HCELL(+) MSCs resulted in durable reversal of hyperglycemia, whereas only transient reversal was observed following administration of HCELL(-) MSCs. Notably, exofucosylation of MSCs generated from CD44(-/-) mice induced prominent membrane expression of sLe(x) , but IV administration of these MSCs into hyperglycemic NOD mice showed no enhanced pancreatotropism or reversal of hyperglycemia. These findings provide evidence that glycan engineering to enforce HCELL expression boosts trafficking of infused MSCs to pancreatic islets of NOD mice and substantially improves their efficacy in reversing autoimmune diabetes. Stem Cells

  6. Novel application of stem cell-derived factors for periodontal regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Inukai, Takeharu, E-mail: t-inukai@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Katagiri, Wataru, E-mail: w-kat@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Yoshimi, Ryoko, E-mail: lianzi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Osugi, Masashi, E-mail: masashi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Kawai, Takamasa, E-mail: takamasa@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Hibi, Hideharu, E-mail: hibihi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Ueda, Minoru, E-mail: mueda@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer Mesenchymal stem cells (MSCs) secrete a variety of cytokines. Black-Right-Pointing-Pointer Cytokines were detected in conditioned medium from cultured MSCs (MSC-CM). Black-Right-Pointing-Pointer MSC-CM enhanced activation of dog MSCs and periodontal ligament cells. Black-Right-Pointing-Pointer MSC-CM significantly promoted alveolar bone and cementum regeneration. Black-Right-Pointing-Pointer Multiple cytokines contained in MSC-CM promote periodontal regeneration. -- Abstract: The effect of conditioned medium from cultured mesenchymal stem cells (MSC-CM) on periodontal regeneration was evaluated. In vitro, MSC-CM stimulated migration and proliferation of dog MSCs (dMSCs) and dog periodontal ligament cells (dPDLCs). Cytokines such as insulin-like growth factor, vascular endothelial growth factor, transforming growth factor-{beta}1, and hepatocyte growth factor were detected in MSC-CM. In vivo, one-wall critical-size, intrabony periodontal defects were surgically created in the mandible of dogs. Dogs with these defects were divided into three groups that received MSC-CM, PBS, or no implants. Absorbable atelo-collagen sponges (TERUPLUG Registered-Sign ) were used as a scaffold material. Based on radiographic and histological observation 4 weeks after transplantation, the defect sites in the MSC-CM group displayed significantly greater alveolar bone and cementum regeneration than the other groups. These findings suggest that MSC-CM enhanced periodontal regeneration due to multiple cytokines contained in MSC-CM.

  7. APPLICATION OF MSC ADAMS – NX NASTRAN/FEMAP INTERFACE IN STRENGTH CALCULATIONS OF TRUCK FRAMES

    Directory of Open Access Journals (Sweden)

    Adam PRZEMYK

    2016-06-01

    Full Text Available In this paper, the finite element method (FEM is used to calculate the strength of truck frames by integrating the MSC Adams software, for dynamics analysis of mechanical systems, and the NX Nastran/Femap software. At the same time, a method for reducing degrees of freedom is been developed based on the Craig–Bampton method. The interface is applied in order to calculate the strength of the frame in the selected truck, which runs on the test track. The selected model of truck can be treated as the virtual prototype that is useful in the design process.

  8. DYNAMIC ANALYSIS OF A CRIMPING DEVICE WITH MULTIPLE CAMS USING MSC ADAMS II

    Directory of Open Access Journals (Sweden)

    Gheorghe Popescu

    2012-05-01

    Full Text Available Through the present paper, the author presents the results of the dynamic analysis with MSC ADAMS of the mechanism with a crimping device with 12 tightening cams, designed and used in the technological process of assembly of the indigenous electrical detonators. In this sense, the mechanism with multiple cams is considered a mechanical system and is treated as an assembly of rigid bodies connected by mechanical connections and elastic elements. For shaping and simulation of the mechanism with multiple cams using ADAMS program, the author got through the following stages: construction of the pattern, its testing and simulation, validation, finishing, parametrization, optimization of the pattern.

  9. Parameters in three-dimensional osteospheroids of telomerized human mesenchymal (stromal) stem cells grown on osteoconductive scaffolds that predict in vivo bone-forming potential

    DEFF Research Database (Denmark)

    Burns, Jorge S; Hansen, Pernille Lund; Larsen, Kenneth H;

    2010-01-01

    Osteoblastic differentiation of human mesenchymal stem cells (hMSC) in monolayer culture is artefactual, lacking an organized bone-like matrix. We present a highly reproducible microwell protocol generating three-dimensional ex vivo multicellular aggregates of telomerized hMSC (hMSC-telomerase re...

  10. Challenging the Innovation Paradigm

    CERN Document Server

    Sveiby, Karl Erik; Segercrantz, Beata

    2012-01-01

    Innovation is almost always seen as a "good thing". Challenging the Innovation Paradigm is a critical analysis of the innovation frenzy and contemporary innovation research. The one-sided focus on desirable effects of innovation misses many opportunities to reduce the undesirable consequences. Authors in this book show how systemic effects outside the innovating firms reduce the net benefits of innovation for individual employees, customers, as well as for society as a whole - also the innovators' own organizations. This book analyzes the dominant discourses that construct and recons

  11. SUSTAINABLE DEVELOPMENT PARADIGM - SYNOPSIS

    Directory of Open Access Journals (Sweden)

    Constantinescu Andreea

    2014-07-01

    Full Text Available Even if sustainable development is a concept that gained quite recently its scientific prestige, through contribution of researchers its content has upgraded to a high degree of conceptual luggage and, through contribution from governance representatives, has gained an impressive good-practice background. Allowing the use of different methodological premises and conceptual tools, sustainable development paradigm is equipped with all the elements that would allow the opening of new horizons of knowledge. Based on the facility which can operate the concept of sustainable development, the European Union aims to develop both a more competitive economy based on environmental protection as well as a new governance of economic policy. This on one hand demonstrates the sustainable development ability to irradiate creativity towards the establishment of interdisciplinary bridges and on the other hand explains the growing interest of researchers interested in the problem of analyzing in detail this fruitful concept. Launched first as a theoretical framework to serve justify actions responsible for weighting economic growth, the concept of Sustainable Development has quickly become a topic of ethical debate circumscribed to the area of perfectibility of human nature to the necessity registry. In this regard, the philosophical content of this paradigm could not remain outside researchers concerns, who want to provide both policy makers and the general public a wide range of evidence to demonstrate the viability of this paradigm. Academia waits until maximization of the contribution of governance to achieve sustainable economic development, which consists in conjunction of this upward path with the momentum given by public policy sync, perfectly adapted for globalization era and all crises to come. However, because this concept based its structure and composition on three pillars, equally important economy, society and environment any attempt to strengthen

  12. Impact of bacteria and bacterial components on osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Fiedler, Tomas, E-mail: tomas.fiedler@med.uni-rostock.de [Institute for Medical Microbiology, Virology, and Hygiene, Rostock University Medical Center, Schillingallee 70, D-18057 Rostock (Germany); Salamon, Achim; Adam, Stefanie; Herzmann, Nicole [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Taubenheim, Jan [Institute for Medical Microbiology, Virology, and Hygiene, Rostock University Medical Center, Schillingallee 70, D-18057 Rostock (Germany); Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Peters, Kirsten [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany)

    2013-11-01

    Adult mesenchymal stem cells (MSC) are present in several tissues, e.g. bone marrow, heart muscle, brain and subcutaneous adipose tissue. In invasive infections MSC get in contact with bacteria and bacterial components. Not much is known about how bacterial pathogens interact with MSC and how contact to bacteria influences MSC viability and differentiation potential. In this study we investigated the impact of three different wound infection relevant bacteria, Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes, and the cell wall components lipopolysaccharide (LPS; Gram-negative bacteria) and lipoteichoic acid (LTA; Gram-positive bacteria) on viability, proliferation, and osteogenic as well as adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (adMSC). We show that all three tested species were able to attach to and internalize into adMSC. The heat-inactivated Gram-negative E. coli as well as LPS were able to induce proliferation and osteogenic differentiation but reduce adipogenic differentiation of adMSC. Conspicuously, the heat-inactivated Gram-positive species showed the same effects on proliferation and adipogenic differentiation, while its cell wall component LTA exhibited no significant impact on adMSC. Therefore, our data demonstrate that osteogenic and adipogenic differentiation of adMSC is influenced in an oppositional fashion by bacterial antigens and that MSC-governed regeneration is not necessarily reduced under infectious conditions. - Highlights: • Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli bind to and internalize into adMSC. • Heat-inactivated cells of these bacterial species trigger proliferation of adMSC. • Heat-inactivated E. coli and LPS induce osteogenic differentiation of adMSC. • Heat-inactivated E. coli and LPS reduce adipogenic differentiation of adMSC. • LTA does not influence adipogenic or osteogenic differentiation of adMSC.

  13. Comparison of hematopoietic supportive capacity between human fetal and adult bone marrow mesenchymal stem cells in vitro.

    Science.gov (United States)

    Liu, Meng; Yang, Shao-Guang; Xing, Wen; Lu, Shi-Hong; Zhao, Qin-Jun; Ren, Hong-Ying; Chi, Ying; Ma, Feng-Xia; Han, Zhong-Chao

    2011-08-01

    Hematopoietic stem cells (HSC) shift from fetal liver and spleen to bone marrow at neonatal stages and this movement may be due to inductive signals from different microenvironments. Mesenchymal stem cells (MSC) are the precursors of stromal cells in bone marrow microenvironments such as osteoblasts and endothelial cells. Some researchers speculated that fetal bone marrow before birth might be not perfectly suit HSC growth. However, it is still lack of direct evidence to prove this hypothesis. This study was aimed to compare the hematopoietic supportive capacity between human fetal and adult bone marrow MSC in vitro. Adult bone marrow MSC (ABM-MSC) were isolated from three healthy donors and fetal bone marrow MSC (FBM-MSC) were isolated from three fetuses between gestations of 19 to 20 weeks. After irradiation, MSC were co-cultured with CD34(+) cells isolated from umbilical cord blood in long-term culture-initiating cell (LTC-IC) assay. The colony number of colony forming cells (CFC) was counted and the phenotypic changes of co-cultured CD34(+) cells were analyzed by flow cytometry. Cytokine expressions in both kinds of MSC were detected by reverse transcription polymerase chain reaction (RT-PCR). The results showed that ABM-MSC had a stronger hematopoietic supportive capacity than FBM-MSC. Both of them enhanced the differentiation of CD34(+) cells into myeloid lineages. Cytokines were expressed differently in ABM-MSC and FBM-MSC. It is concluded that ABM-MSC possess more potential application in some treatments than FBM-MSC, especially in hematopoietic reconstitution.

  14. Cellulose-based porous scaffold for bone tissue engineering applications: Assessment of hMSC proliferation and differentiation.

    Science.gov (United States)

    Demitri, Christian; Grazia Raucci, Maria; Giuri, Antonella; De Benedictis, Vincenzo Maria; Giugliano, Daniela; Calcagnile, Paola; Sannino, Alessandro; Ambrosio, Luigi

    2015-10-31

    Physical foaming combined with microwave-induced curing was used in this study to develop an innovative device for bone tissue regeneration. In the first step of the process, a stable physical foaming was induced using a surfactant (i.e. pluronic) as blowing agent of a homogeneous blend of Sodium salt of carboxymethylcellulose (CMCNa) and polyethylene glycol diacrylate (PEGDA700) solution. In the second step, the porous structure of the scaffold was chemically stabilized by radical polymerization induced by a homogeneous rapid heating of the sample in a microwave reactor. In this step 2,2-Azobis[2-(2-imidazolin-2 yl)propane]Dihydrochloride was used as thermoinitiator (TI). CMCNa and PEGDA were mixed with different blends to correlate the properties of final product with the composition. The chemical properties of each sample were evaluated by spectroscopy analysis ATR-IR (before and after curing) in order to maximize reaction yield, and optimize kinetic parameters (i.e. time curing, microwave power). The stability of the materials was evaluated in vitro by degradation test in Phosphate Buffered Saline (PBS). Biological analyses were performed to evaluate the effect of scaffold materials on cellular behaviour in terms of proliferation and early osteogenic differentiation of human Mesenchymal Stem Cells (hMSC). This article is protected by copyright. All rights reserved.

  15. Marketing! Where is Paradigm?

    Directory of Open Access Journals (Sweden)

    Deosir Flávio Lobo de Castro Júnior

    2015-09-01

    Full Text Available The quantitative- qualitative debate is not a new discussion. The aim of this study therefore is to check through the concept of paradigm, new perspectives to understand the academic research in marketing, developments of marketing thinking and methodologies used in the studies of quality of service. Without pretending to exhaust the subject and present a final conclusion, studies that point to the need and importance of qualitative research, as it helps the researcher to better understand the complex nature of the social world in which we live are presented. According to Santana and Gomes (2007, after examining the discussion of Hegel and Kant, reason and conclude that epistemology itself are historical buildings and evolve from contradictions. This article is divided into five moments. The first part presents besides introducing the constitution of the goals of this theoretical essay. The second part presents a brief discussion of the concept of paradigm and marketing. The third part presents a historical retrospective of marketing and its evolution from its schools from studies of Miranda and Arruda (2004. The fourth part presents the methodology of the studies on quality of services and finally the fifth part presents the final considerations.

  16. Structural and magnetic properties of Ti12M clusters (M=Sc to Zn)

    Science.gov (United States)

    Sun, Houqian; Xu, Ning

    2016-12-01

    The geometries, electronic, and magnetic properties of the 3d atom doped icosahedron (ICO) Ti12M (M=Sc to Zn), where a dopant atom replaces either the centra l(Ti12Mc) or surface (Ti12Ms) Ti atom in ICO Ti13 cluster, have been systematically investigated by using the density functional theory. The structures of all the optimized Ti12Mc and Ti12Ms clusters are distorted ICO. Sc, Ni, Cu, and Zn atoms prefer to displace surface Ti atom, V, Cr, Mn, and Fe atoms prefer to displace central Ti atom. The position of impurity atom depends on the strength of the interaction between the central atom and the surface atoms. As compared to the pure Ti13 cluster, Ti12Mc and Ti12Ms (M=V, Fe, Co, and Ni) clusters are more stable, Ti12Mc and Ti12Ms (M=Sc, Cr, Mn, Cu, and Zn) are less stable. Both Ti12Nis and Ti12Nic are magic clusters, which originate from their electronic as well as geometric closed shells. Because the exchange interaction prevails over the crystal field in Ti12M clusters, the valence electrons fill molecular orbitals in terms of Hund's rule of maximum spin.

  17. Transient Analysis of Thermal Protection System for X-33 Aircraft using MSC/NASTRAN

    Science.gov (United States)

    Miura, Hirokazu; Chargin, M. K.; Bowles, J.; Tam, T.; Chu, D.; Chainyk, M.; Green, Michael J. (Technical Monitor)

    1997-01-01

    X-33 is an advanced technology demonstrator vehicle for the Reusable Launch Vehicle (RLV) program. The thermal protection system (TPS) for the X-33 is composed of complex layers of materials to protect internal components, while withstanding severe external temperatures induced by aerodynamic heating during high speed flight. It also serves as the vehicle aeroshell in some regions using a stand-off design. MSC/NASTRAN thermal analysis capability was used to predict transient temperature distribution (within the TPS) throughout a mission, from launch through the cool-off period after landing. In this paper, a typical analysis model, representing a point on the vehicle where the liquid oxygen tank is closest to the outer mold line, is described. The maximum temperature difference between the outer mold line and the internal surface of the liquid oxygen tank can exceed 1500 F. One dimensional thermal models are used to select the materials and determine the thickness of each layer for minimum weight while insuring that all materials remain within the allowable temperature range. The purpose of working with three dimensional (3D) comprehensive models using MSC/NASTRAN is to assess the 3D radiation effects and the thermal conduction heat shorts of the support fixtures.

  18. Efficacy of immunotherapy with mesenchymal stem cells in man: a systematic review.

    Science.gov (United States)

    Luk, Franka; de Witte, Samantha F H; Bramer, Wichor M; Baan, Carla C; Hoogduijn, Martin J

    2015-05-01

    Mesenchymal stem cells (MSC) are widely studied for their immunomodulatory properties. Data from in vitro and pre-clinical models demonstrate that MSC suppress activated immune cells and ameliorate the severity of experimental immune disease. In complex human studies, the immunomodulatory efficacy of MSC therapy is not well established. We conducted a systematic review of clinical studies which used MSC with the purpose of immunomodulation and included at least 10 patients to investigate the efficacy of MSC therapy. Sixty-two studies comprising 10 different immune disorders were included in the analysis, of which 18 studies represented controlled trials. Although several of the studies reported an amelioration of disease severity, other studies failed to observe a beneficial effect of MSC. The low number of randomized controlled trials, small number of studies per disease category and limited immunological readout parameters made it difficult to draw a definitive conclusion on the efficacy of MSC immune therapy.

  19. Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study.

    Science.gov (United States)

    Moodley, Yuben; Vaghjiani, Vijesh; Chan, James; Baltic, Svetlana; Ryan, Marisa; Tchongue, Jorge; Samuel, Chrishan S; Murthi, Padma; Parolini, Ornella; Manuelpillai, Ursula

    2013-01-01

    Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.

  20. Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study.

    Directory of Open Access Journals (Sweden)

    Yuben Moodley

    Full Text Available Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC, bone marrow MSC (BM-MSC and human amniotic epithelial cells (hAEC in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC, IL-6 (AM-MSC, BM-MSC, hAEC and TNF-α (AM-MSC. The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC. IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.

  1. Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice

    DEFF Research Database (Denmark)

    Niemeyer, P; Vohrer, J; Schmal, H

    2008-01-01

    INTRODUCTION: Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose...... of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice. METHODS: Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were...... osteogenic-induced MSC (group B) could be detected in only three of 24 cases. Quantification of lymphocytes and macrophages revealed significantly higher cell numbers in group B compared with group A (Pcell...

  2. Human Adipose Tissue-Derived Mesenchymal Stem Cells Abrogate Plasmablast Formation and Induce Regulatory B Cells Independently of T Helper Cells

    NARCIS (Netherlands)

    Franquesa, M.; Mensah, F. K.; Huizinga, R.; Strini, T.; Boon, L.; Lombardo, E.; DelaRosa, O.; Laman, J. D.; Grinyo, J. M.; Weimar, W.; Betjes, M. G. H.; Baan, C. C.; Hoogduijn, M. J.

    2015-01-01

    Mesenchymal or stromal stem cells (MSC) interact with cells of the immune system in multiple ways. Modulation of the immune system by MSC is believed to be a therapeutic option for autoimmune disease and transplant rejection. In recent years, B cells have moved into the focus of the attention as tar

  3. Avoidance of Maternal Cell Contamination and Overgrowth in Isolating Fetal Chorionic Villi Mesenchymal Stem Cells from Human Term Placenta.

    Science.gov (United States)

    Sardesai, Varda S; Shafiee, Abbas; Fisk, Nicholas M; Pelekanos, Rebecca A

    2017-04-01

    Human placenta is rich in mesenchymal stem/stromal cells (MSC), with their origin widely presumed fetal. Cultured placental MSCs are confounded by a high frequency of maternal cell contamination. Our recent systematic review concluded that only a small minority of placental MSC publications report fetal/maternal origin, and failed to discern a specific methodology for isolation of fetal MSC from term villi. We determined isolation conditions to yield fetal and separately maternal MSC during ex vivo expansion from human term placenta. MSCs were isolated via a range of methods in combination; selection from various chorionic regions, different commercial media, mononuclear cell digest and/or explant culture. Fetal and maternal cell identities were quantitated in gender-discordant pregnancies by XY chromosome fluorescence in situ hybridization. We first demonstrated reproducible maternal cell contamination in MSC cultures from all chorionic anatomical locations tested. Cultures in standard media rapidly became composed entirely of maternal cells despite isolation from fetal villi. To isolate pure fetal cells, we validated a novel isolation procedure comprising focal dissection from the cotyledonary core, collagenase/dispase digestion and explant culture in endothelial growth media that selected, and provided a proliferative environment, for fetal MSC. Comparison of MSC populations within the same placenta confirmed fetal to be smaller, more osteogenic and proliferative than maternal MSC. We conclude that in standard media, fetal chorionic villi-derived MSC (CV-MSC) do not grow readily, whereas maternal MSC proliferate to result in maternal overgrowth during culture. Instead, fetal CV-MSCs require isolation under specific conditions, which has implications for clinical trials using placental MSC. Stem Cells Translational Medicine 2017;6:1070-1084.

  4. The Peter Pan paradigm

    Directory of Open Access Journals (Sweden)

    Larson Janet E

    2008-01-01

    Full Text Available Abstract Genetic and environmental agents that disrupt organogenesis are numerous and well described. Less well established, however, is the role of delay in the developmental processes that yield functionally immature tissues at birth. Evidence is mounting that organs do not continue to develop postnatally in the context of these organogenesis insults, condemning the patient to utilize under-developed tissues for adult processes. These poorly differentiated organs may appear histologically normal at birth but with age may deteriorate revealing progressive or adult-onset pathology. The genetic and molecular underpinning of the proposed paradigm reveals the need for a comprehensive systems biology approach to evaluate the role of maternal-fetal environment on organogenesis. You may delay, but time will not Benjamin Franklin USA Founding Father

  5. The Peter Pan paradigm.

    Science.gov (United States)

    Cohen, J Craig; Larson, Janet E

    2008-01-08

    Genetic and environmental agents that disrupt organogenesis are numerous and well described. Less well established, however, is the role of delay in the developmental processes that yield functionally immature tissues at birth. Evidence is mounting that organs do not continue to develop postnatally in the context of these organogenesis insults, condemning the patient to utilize under-developed tissues for adult processes. These poorly differentiated organs may appear histologically normal at birth but with age may deteriorate revealing progressive or adult-onset pathology. The genetic and molecular underpinning of the proposed paradigm reveals the need for a comprehensive systems biology approach to evaluate the role of maternal-fetal environment on organogenesis."You may delay, but time will not" Benjamin Franklin, USA Founding Father.

  6. PARADIGM OF ACCOUNTING CHANGE

    Directory of Open Access Journals (Sweden)

    Constanta Iacob

    2016-12-01

    Full Text Available The words and phrases swop with each other and the apparent stability of a word’s meaning sometimes change in time. This explains why the generic term of accounting is used when referring to the qualities attributed to accounting,but also when it comes to organizing financial accounting function within the entity, and when referring concretely to keeping a double record with its specific means, methods and tools specific, respectively seen as a technical accounting.Speaking about the qualities of accounting, but also about the organizational form it takes, we note that there is a manifold meaning of the word accounting, which is why the purpose of this article is to demonstrate that the paradigm shift aimed at a new set of rules and if the rules changes, then we can change the very purpose of accounting.

  7. Paradigms for parasite conservation.

    Science.gov (United States)

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  8. Mesenchymal Stem Cell-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Ameliorate Diabetic Polyneuropathy in Mice

    Directory of Open Access Journals (Sweden)

    Tatsuhito Himeno

    2013-01-01

    Full Text Available Background. Although pathological involvements of diabetic polyneuropathy (DPN have been reported, no dependable treatment of DPN has been achieved. Recent studies have shown that mesenchymal stem cells (MSCs ameliorate DPN. Here we demonstrate a differentiation of induced pluripotent stem cells (iPSCs into MSC-like cells and investigate the therapeutic potential of the MSC-like cell transplantation on DPN. Research Design and Methods. For induction into MSC-like cells, GFP-expressing iPSCs were cultured with retinoic acid, followed by adherent culture for 4 months. The MSC-like cells, characterized with flow cytometry and RT-PCR analyses, were transplanted into muscles of streptozotocin-diabetic mice. Three weeks after the transplantation, neurophysiological functions were evaluated. Results. The MSC-like cells expressed MSC markers and angiogenic/neurotrophic factors. The transplanted cells resided in hindlimb muscles and peripheral nerves, and some transplanted cells expressed S100β in the nerves. Impairments of current perception thresholds, nerve conduction velocities, and plantar skin blood flow in the diabetic mice were ameliorated in limbs with the transplanted cells. The capillary number-to-muscle fiber ratios were increased in transplanted hindlimbs of diabetic mice. Conclusions. These results suggest that MSC-like cell transplantation might have therapeutic effects on DPN through secreting angiogenic/neurotrophic factors and differentiation to Schwann cell-like cells.

  9. Adult Stromal (Skeletal, Mesenchymal) Stem Cells: Advances Towards Clinical Applications

    DEFF Research Database (Denmark)

    Kermani, Abbas Jafari; Harkness, Linda; Zaher, Walid;

    2014-01-01

    Mesenchymal Stem Cells (MSC) are non-hematopoietic adult stromal cells that reside in a perivascular niche in close association with pericytes and endothelial cells and possess self-renewal and multi-lineage differentiation capacity. The origin, unique properties, and therapeutic benefits of MSC ...

  10. 基于MSC.fatigue的某轻型客车车架疲劳寿命分析%Fatigue Analysis for Light-bus Frame Based on MSC.fatigue

    Institute of Scientific and Technical Information of China (English)

    惠延波; 王宏晓; 冯兰芳; 夏兆义; 王瞧; 邢志伟

    2013-01-01

    Based upon the fatigue crack problems of a light-bus hybrid vehicle frame after run 5 ,000 km, a fatigue crack simulation is done for this with the comprehensive application of multi-body dynamics, finite element analysis and fatigue analysis. A multi-body model is set up in MSC. Adams/Car with load spectra of B-grade road acquired, a static analysis is conducted by using inertia relief technique in MSC. Nastran, a fatigue life analysis is performed in MSC. Fatigue, the main reasons that lead to fatigue breach is analyzed to find out. One measure is proposed to pick out according to demand. In the end, the verification of the modified model and the comparison of the fatigue life between the prior and the modified project was done.%针对某轻型客车杂合车在路试5 000 km时车架出现疲劳裂纹的问题,综合采用多体动力学、有限元和疲劳分析方法对其进行疲劳破坏仿真.在MSC.Adams/Car中建立该车的多体动力学模型得到其在B级路面的载荷历程,在MSC.Nastran中采用惯性释放方法对其进行静力学分析,在MSC.Fatigue中对其进行疲劳寿命分析,通过对结果深入研究,找到该车架产生疲劳裂纹的主要原因,提出了合理的改进方案,最后对改进后的车架结构进行了寿命对比验证.

  11. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demuth, Christina; Safwat, Akmal;

    2016-01-01

    growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI....... However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin....

  12. The Consumption Paradigm in Marketing

    OpenAIRE

    Ardianto, Eka

    2003-01-01

    This article elaborates consumption paradigm in marketing. In background, this paper reviews different perspectives of consumption: economic perspective and marketing perspective. In ontology, this work describes various issues regarding consumption view. In epistemology, this article demonstrates how marketers especially researches explore the consumption phenomena. In methodology, the article describes experiential marketing –one of applied consumption paradigm in marketing, which could be ...

  13. Overexpression of Heme Oxygenase-1 in Mesenchymal Stem Cells Augments Their Protection on Retinal Cells In Vitro and Attenuates Retinal Ischemia/Reperfusion Injury In Vivo against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Li Li

    2017-01-01

    Full Text Available Retinal ischemia/reperfusion (I/R injury, involving several ocular diseases, seriously threatens human ocular health, mainly treated by attenuating I/R-induced oxidative stress. Currently, mesenchymal stem cells (MSCs could restore I/R-injured retina through paracrine secretion. Additionally, heme oxygenase-1 (HO-1 could ameliorate oxidative stress and thus retinal apoptosis, but the expression of HO-1 in MSC is limited. Here, we hypothesized that overexpression of HO-1 in MSC (MSC-HO-1 may significantly improve their retina-protective potentials. The overexpression of HO-1 in MSC was achieved by lentivirus transduction. Then, MSC or MSC-HO-1 was cocultured with retinal ganglion cells (RGC-5 in H2O2-simulated oxidative condition and their protection on RGC-5 was systemically valuated in vitro. Compared with MSC, MSC-HO-1 significantly attenuated H2O2-induced injury of RGC-5, including decrease in cellular ROS level and apoptosis, activation of antiapoptotic proteins p-Akt and Bcl-2, and blockage of proapoptotic proteins cleaved caspase 3 and Bax. In retinal I/R rats model, compared with control MSC, MSC-HO-1-treated retina significantly retrieved its structural thickness, reduced cell apoptosis, markedly attenuated retinal oxidative stress level, and largely regained the activities of typical antioxidant enzymes, SOD and CAT. Therefore, it could be concluded that overexpression of HO-1 provides a promising strategy to enhance the MSC-based therapy for I/R-related retinal injury.

  14. Effect of mitochondrial genome rearrangement on respiratory activity, photosynthesis, photorespiration and energy status of MSC16 cucumber (Cucumis sativus) mutant.

    Science.gov (United States)

    Juszczuk, Izabela M; Flexas, Jaume; Szal, Bozena; Dabrowska, Zofia; Ribas-Carbo, Miquel; Rychter, Anna M

    2007-12-01

    The effects of changes in mitochondrial DNA in cucumber (Cucumis sativus L.) mosaic mutant (MSC16) on respiration, photosynthesis and photorespiration were analyzed under non-stressed conditions. Decreased respiratory capacity of complex I in MSC16 mitochondria was indicated by lower respiration rates of intact mitochondria with malate and by rotenone-inhibited NADH or malate oxidation in the presence of alamethicin. Moreover, blue native PAGE indicated decreased intensity of protein bands of respiratory chain complex I in MSC16 leaves. Concerning the redox state, complex I impairment could be compensated to some extent by increased external NADH dehydrogenases (ND(ex)NADH) and alternative oxidase (AOX) capacity, the latter presenting differential expression in the light and in the dark. Although MSC16 mitochondria have a higher AOX protein level and an increased capacity, the AOX activity measured in the dark conditions by oxygen discrimination technique is similar to that in wild-type (WT) plants. Photosynthesis induction by light followed different patterns in WT and MSC16, suggesting changes in feedback chloroplast DeltapH caused by different adenylate levels. At steady-state, net photosynthesis was only slightly impaired in MSC16 mutants, while photorespiration rate (PR) was significantly increased. This was the result of large decreases in both stomatal and mesophyll conductance to CO2, which resulted in a lower CO2 concentration in the chloroplasts. The observed changes on CO2 diffusion caused by mitochondrial mutations open a whole new view of interaction between organelle metabolism and whole tissue physiology. The sum of all the described changes in photosynthetic and respiratory metabolism resulted in a lower ATP availability and a slower plant growth.

  15. Prenatal transplantation of mesenchymal stem cells to treat osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Jerry KY Chan

    2014-10-01

    Full Text Available Osteogenesis Imperfecta (OI can be a severe disorder that can be diagnosed before birth. Transplantation of mesenchymal stem cells (MSC has the potential to improve the bone structure, growth and fracture healing. In this review we give an introduction to OI and MSC, and the basis for prenatal and postnatal transplantation in OI. We also summarize the two patients with OI who has received prenatal and postnatal transplantation of MSC.The findings suggest that prenatal transplantation of allogeneic MSC in OI is safe. The cell therapy is of likely clinical benefit with improved linear growth, mobility and reduced fracture incidence. Unfortunately, the effect is transient. For this reason postnatal booster infusions using same-donor MSC have been performed with clinical benefit, and without any adverse events.So far there is limited experience in this specific field and proper studies are required to accurately conclude on clinical benefits of MSC transplantation to treat OI.

  16. Stem cell technology for bone regeneration: current status and potential applications

    Directory of Open Access Journals (Sweden)

    Asatrian G

    2015-02-01

    Full Text Available Greg Asatrian,1 Dalton Pham,1,2 Winters R Hardy,3 Aaron W James,1–3 Bruno Peault3,4 1Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, 2Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, 3UCLA/Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, CA, USA; 4Medical Research Council Centre for Regenerative Medicine, Edinburgh, Scotland, UK Abstract: Continued improvements in the understanding and application of mesenchymal stem cells (MSC have revolutionized tissue engineering. This is particularly true within the field of skeletal regenerative medicine. However, much remains unknown regarding the native origins of MSC, the relative advantages of different MSC populations for bone regeneration, and even the biologic safety of such unpurified, grossly characterized cells. This review will first summarize the initial discovery of MSC, as well as the current and future applications of MSC in bone tissue engineering. Next, the relative advantages and disadvantages of MSC isolated from distinct tissue origins are debated, including the MSC from adipose, bone marrow, and dental pulp, among others. The perivascular origin of MSC is next discussed. Finally, we briefly comment on pluripotent stem cell populations and their possible application in bone tissue engineering. While continually expanding, the field of MSC-based bone tissue engineering and regeneration shows potential to become a clinical reality in the not-so-distant future.Keywords: mesenchymal stem cell, pericyte, bone tissue engineering, MSC, ASC, DMSC

  17. Cause of Errors Associated with Application of Drucker-Prager Yield Criterion in MSC/NASTRAN Program%MSC/NASTRAN程序中Drucker-Prager屈服准则引起误差的原因探讨

    Institute of Scientific and Technical Information of China (English)

    王进军

    2000-01-01

    When the Drucker-Prager yield criterion is used, the MSC/NASTRAN program frequently predicts noticeable errors. The relevant part of NASTRAN Handbook was checked and some errors in the elasto-plastics theory used in NASTRAN were detected in this paper. The procurement to prove these errors was verified by numerical calculation.

  18. Stem cells to regenerate the newborn brain

    NARCIS (Netherlands)

    van Velthoven, C.T.J.

    2011-01-01

    Perinatal hypoxia-ischemia (HI) is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. In this thesis we investigate whether mesenchymal stem cells (MSC) regenerate the neonatal brain after HI injury. We show that transplantation of MSC after neonatal brain injury

  19. Human bone-marrow-derived mesenchymal stem cells

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment of a var......Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment...... of a variety of clinical conditions. The aim of this review is to provide an update regarding the biology of MSC, their identification and culture, and mechanisms controlling their proliferation and differentiation. We also review the current status of their clinical use. Areas in which research is needed...

  20. Läätsa Kalatööstus järjekordne MSC sertifikaadi omanik / Alar Mik

    Index Scriptorium Estoniae

    Mik, Alar

    2014-01-01

    MSC (Marine Stewardship Council)-märgis toodetel tõendab, et tegemist on keskkonnaalaselt vastutustundliku ettevõttega, kelle toodangutsükkel on kala püüdmisest kuni valmistoodangu tarbijani jõudmiseni rangelt seaduslik ja keskkonnasäästlik. Vestlusest ettevõtte juhatuse liikme Toomas Auliga

  1. Capacity Building in IWRM: The IWRM MSc Curriculum at the Water and Environment Centre, Republic of Yemen

    NARCIS (Netherlands)

    Soppe, R.W.O.; Babaqi, A.S.; Huibers, F.P.

    2005-01-01

    Integrated Water Resources Management (IWRM) is an interdisciplinary approach to water resources management, as opposed to water resources development. In developing an MSc curriculum at the Water and Environment Centre (WEC) at Sana'a University in the republic of Yemen, three goals were defined. T

  2. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging.

    Science.gov (United States)

    Kidd, Shannon; Spaeth, Erika; Dembinski, Jennifer L; Dietrich, Martin; Watson, Keri; Klopp, Ann; Battula, Venkata Lokesh; Weil, Micheal; Andreeff, Michael; Marini, Frank C

    2009-10-01

    Multipotent mesenchymal stromal/stem cells (MSC) have shown potential clinical utility. However, previous assessments of MSC behavior in recipients have relied on visual detection in host tissue following sacrifice, failing to monitor in vivo MSC dispersion in a single animal and limiting the number of variables that can be observed concurrently. In this study, we used noninvasive, in vivo bioluminescent imaging to determine conditions under which MSC selectively engraft in sites of inflammation. MSC modified to express firefly luciferase (ffLuc-MSC) were injected into healthy mice or mice bearing inflammatory insults, and MSC localization was followed with bioluminescent imaging. The inflammatory insults investigated included cutaneous needle-stick and surgical incision wounds, as well as xenogeneic and syngeneic tumors. We also compared tumor models in which MSC were i.v. or i.p. delivered. Our results demonstrate that ffLuc-expressing human MSC (hMSC) systemically delivered to nontumor-bearing animals initially reside in the lungs, then egress to the liver and spleen, and decrease in signal over time. However, hMSC in wounded mice engraft and remain detectable only at injured sites. Similarly, in syngeneic and xenogeneic breast carcinoma-bearing mice, bioluminescent detection of systemically delivered MSC revealed persistent, specific colocalization with sites of tumor development. This pattern of tropism was also observed in an ovarian tumor model in which MSC were i.p. injected. In this study, we identified conditions under which MSC tropism and selective engraftment in sites of inflammation can be monitored by bioluminescent imaging over time. Importantly, these consistent findings were independent of tumor type, immunocompetence, and route of MSC delivery.

  3. Delivery of human mesenchymal adipose-derived stem cells restores multiple urological dysfunctions in a rat model mimicking radical prostatectomy damages through tissue-specific paracrine mechanisms.

    Science.gov (United States)

    Yiou, René; Mahrouf-Yorgov, Meriem; Trébeau, Céline; Zanaty, Marc; Lecointe, Cécile; Souktani, Richard; Zadigue, Patricia; Figeac, Florence; Rodriguez, Anne-Marie

    2016-02-01

    Urinary incontinence (UI) and erectile dysfunction (ED) are the most common functional urological disorders and the main sequels of radical prostatectomy (RP) for prostate cancer. Mesenchymal stem cell (MSC) therapy holds promise for repairing tissue damage due to RP. Because animal studies accurately replicating post-RP clinical UI and ED are lacking, little is known about the mechanisms underlying the urological benefits of MSC in this setting. To determine whether and by which mechanisms MSC can repair damages to both striated urethral sphincter (SUS) and penis in the same animal, we delivered human multipotent adipose stem cells, used as MSC model, in an immunocompetent rat model replicating post-RP UI and ED. In this model, we demonstrated by using noninvasive methods in the same animal from day 7 to day 90 post-RP injury that MSC administration into both the SUS and the penis significantly improved urinary continence and erectile function. The regenerative effects of MSC therapy were not due to transdifferentiation and robust engraftment at injection sites. Rather, our results suggest that MSC benefits in both target organs may involve a paracrine process with not only soluble factor release by the MSC but also activation of the recipient's secretome. These two effects of MSC varied across target tissues and damaged-cell types. In conclusion, our work provides new insights into the regenerative properties of MSC and supports the ability of MSC from a single source to repair multiple types of damage, such as those seen after RP, in the same individual.

  4. Towards reduction of Paradigm coordination models

    CERN Document Server

    Andova, Suzana; de Vink, Erik; 10.4204/EPTCS.60.1

    2011-01-01

    The coordination modelling language Paradigm addresses collaboration between components in terms of dynamic constraints. Within a Paradigm model, component dynamics are consistently specified at a detailed and a global level of abstraction. To enable automated verification of Paradigm models, a translation of Paradigm into process algebra has been defined in previous work. In this paper we investigate, guided by a client-server example, reduction of Paradigm models based on a notion of global inertness. Representation of Paradigm models as process algebraic specifications helps to establish a property-preserving equivalence relation between the original and the reduced Paradigm model. Experiments indicate that in this way larger Paradigm models can be analyzed.

  5. Unsaturated fatty acids induce mesenchymal stem cells to increase secretion of angiogenic mediators.

    Science.gov (United States)

    Smith, Andria N; Muffley, Lara A; Bell, Austin N; Numhom, Surawej; Hocking, Anne M

    2012-09-01

    Mesenchymal stem cells (MSC) represent emerging cell-based therapies for diabetes and associated complications. Ongoing clinical trials are using exogenous MSC to treat type 1 and 2 diabetes, cardiovascular disease and non-healing wounds due to diabetes. The majority of these trials are aimed at exploiting the ability of these multipotent mesenchymal stromal cells to release soluble mediators that reduce inflammation and promote both angiogenesis and cell survival at sites of tissue damage. Growing evidence suggests that MSC secretion of soluble factors is dependent on tissue microenvironment. Despite the contribution of fatty acids to the metabolic environment of type 2 diabetes, almost nothing is known about their effects on MSC secretion of growth factors and cytokines. In this study, human bone marrow-derived MSC were exposed to linoleic acid, an omega-6 polyunsaturated fatty acid, or oleic acid, a monounsaturated fatty acid, for seven days in the presence of 5.38 mM glucose. Outcomes measured included MSC proliferation, gene expression, protein secretion and chemotaxis. Linoleic and oleic acids inhibited MSC proliferation and altered MSC expression and secretion of known mediators of angiogenesis. Both unsaturated fatty acids induced MSC to increase secretion of interleukin-6, VEGF and nitric oxide. In addition, linoleic acid but not oleic acid induced MSC to increase production of interleukin-8. Collectively these data suggest that exposure to fatty acids may have functional consequences for MSC therapy. Fatty acids may affect MSC engraftment to injured tissue and MSC secretion of cytokines and growth factors that regulate local cellular responses to injury.

  6. Exosome: A Novel and Safer Therapeutic Refinement of Mesenchymal Stem Cell

    OpenAIRE

    Yeo, Ronne Wee Yeh; Lai, Ruenn Chai; Tan, Kok Hian; Lim, Sai Kiang

    2013-01-01

    Mesenchymal stem cell (MSC) has just been approved as the first “off-the-shelf” stem cell pharmaceutical drug with an anticipation of more approvals following completion of numerous rigorous clinical trials. Despite this progress, the rationale for MSC therapeutic efficacy remains tenuous and is increasingly rationalized on a secretion rather than differentiation mechanism. Recent studies identifying exosome as the secreted agent mediating MSC therapeutic efficacy coul...

  7. PARADIGM SHIFT IN ISLAMIC STUDIES

    Directory of Open Access Journals (Sweden)

    Editor Al-Jami'ah: Journal of Islamic Studies

    2008-08-01

    Full Text Available In the early 1990s, there was a heated debate among students ofIAIN (the State Institute for Islamic Studies Sunan KalijagaYogyakarta about the future of Islamic studies, focusing on the possibilityof incorporating Thomas Kuhn’s paradigm to the discourse ofIslamic studies. Kuhn explains in detail the rise and decline of scientificparadigm in his classic work, The Structure of Scientific Revolutions,firstly published in 1970. Paradigm is defined as a set of beliefs thatguides the researchers to address some important problems or issuesunder a certain theoretical framework and provides procedures how tosolve those problems. A paradigm shift is a process whereby a newway of perceiving the world comes into existence and is accepted byscholars in a given time. Kuhn proposed two conditions for paradigmshift; first, the presence of anomalies in ‘normal science’, and secondly,the presence of alternative paradigm.

  8. Long-lasting inhibitory effects of fetal liver mesenchymal stem cells on T-lymphocyte proliferation.

    Directory of Open Access Journals (Sweden)

    Massimo Giuliani

    Full Text Available Human bone marrow mesenchymal stem cells (BM-MSC are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK cells, Dendritic Cells (DC, and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb, cyclins A and D1, as well as up-regulating p27(kip1 expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4(low/CD8(low T subset that had decreased secretion of IFN-γ, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection.

  9. Endothelial cells influence the osteogenic potential of bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Arvidson Kristina

    2009-11-01

    Full Text Available Abstract Background Improved understanding of the interactions between bone cells and endothelial cells involved in osteogenesis should aid the development of new strategies for bone tissue engineering. The aim of the present study was to determine whether direct communication between bone marrow stromal cells (MSC and human umbilical vein endothelial cells (EC could influence the osteogenic potential of MSC in osteogenic factor-free medium. Methods After adding EC to MSC in a direct-contact system, cell viability and morphology were investigated with the WST assay and immnostaining. The effects on osteogenic differentiation of adding EC to MSC was systematically tested by the using Superarray assay and results were confirmed with real-time PCR. Results Five days after the addition of EC to MSC in a ratio of 1:5 (EC/MSC significant increases in cell proliferation and cellular bridges between the two cell types were detected, as well as increased mRNA expression of alkaline phosphatase (ALP. This effect was greater than that seen with addition of osteogenic factors such as dexamethasone, ascorbic acid and β-glycerophosphate to the culture medium. The expression of transcription factor Runx2 was enhanced in MSC incubated with osteogenic stimulatory medium, but was not influenced by induction with EC. The expression of Collagen type I was not influenced by EC but the cells grown in the osteogenic factor-free medium exhibited higher expression than those cultured with osteogenic stimulatory medium. Conclusion These results show that co-culturing of EC and MSC for 5 days influences osteogenic differentiation of MSC, an effect that might be independent of Runx2, and enhances the production of ALP by MSC.

  10. Impact of bacteria and bacterial components on osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells.

    Science.gov (United States)

    Fiedler, Tomas; Salamon, Achim; Adam, Stefanie; Herzmann, Nicole; Taubenheim, Jan; Peters, Kirsten

    2013-11-01

    Adult mesenchymal stem cells (MSC) are present in several tissues, e.g. bone marrow, heart muscle, brain and subcutaneous adipose tissue. In invasive infections MSC get in contact with bacteria and bacterial components. Not much is known about how bacterial pathogens interact with MSC and how contact to bacteria influences MSC viability and differentiation potential. In this study we investigated the impact of three different wound infection relevant bacteria, Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes, and the cell wall components lipopolysaccharide (LPS; Gram-negative bacteria) and lipoteichoic acid (LTA; Gram-positive bacteria) on viability, proliferation, and osteogenic as well as adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (adMSC). We show that all three tested species were able to attach to and internalize into adMSC. The heat-inactivated Gram-negative E. coli as well as LPS were able to induce proliferation and osteogenic differentiation but reduce adipogenic differentiation of adMSC. Conspicuously, the heat-inactivated Gram-positive species showed the same effects on proliferation and adipogenic differentiation, while its cell wall component LTA exhibited no significant impact on adMSC. Therefore, our data demonstrate that osteogenic and adipogenic differentiation of adMSC is influenced in an oppositional fashion by bacterial antigens and that MSC-governed regeneration is not necessarily reduced under infectious conditions.

  11. Conformational state of the MscS mechanosensitive channel in solution revealed by pulsed electron-electron double resonance (PELDOR) spectroscopy.

    Science.gov (United States)

    Pliotas, Christos; Ward, Richard; Branigan, Emma; Rasmussen, Akiko; Hagelueken, Gregor; Huang, Hexian; Black, Susan S; Booth, Ian R; Schiemann, Olav; Naismith, James H

    2012-10-02

    The heptameric mechanosensitive channel of small conductance (MscS) provides a critical function in Escherichia coli where it opens in response to increased bilayer tension. Three approaches have defined different closed and open structures of the channel, resulting in mutually incompatible models of gating. We have attached spin labels to cysteine mutants on key secondary structural elements specifically chosen to discriminate between the competing models. The resulting pulsed electron-electron double resonance (PELDOR) spectra matched predicted distance distributions for the open crystal structure of MscS. The fit for the predictions by structural models of MscS derived by other techniques was not convincing. The assignment of MscS as open in detergent by PELDOR was unexpected but is supported by two crystal structures of spin-labeled MscS. PELDOR is therefore shown to be a powerful experimental tool to interrogate the conformation of transmembrane regions of integral membrane proteins.

  12. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure.

    Directory of Open Access Journals (Sweden)

    Biju Parekkadan

    Full Text Available Modulation of the immune system may be a viable alternative in the treatment of fulminant hepatic failure (FHF and can potentially eliminate the need for donor hepatocytes for cellular therapies. Multipotent bone marrow-derived mesenchymal stem cells (MSCs have been shown to inhibit the function of various immune cells by undefined paracrine mediators in vitro. Yet, the therapeutic potential of MSC-derived molecules has not been tested in immunological conditions in vivo. Herein, we report that the administration of MSC-derived molecules in two clinically relevant forms-intravenous bolus of conditioned medium (MSC-CM or extracorporeal perfusion with a bioreactor containing MSCs (MSC-EB-can provide a significant survival benefit in rats undergoing FHF. We observed a cell mass-dependent reduction in mortality that was abolished at high cell numbers indicating a therapeutic window. Histopathological analysis of liver tissue after MSC-CM treatment showed dramatic reduction of panlobular leukocytic infiltrates, hepatocellular death and bile duct duplication. Furthermore, we demonstrate using computed tomography of adoptively transferred leukocytes that MSC-CM functionally diverts immune cells from the injured organ indicating that altered leukocyte migration by MSC-CM therapy may account for the absence of immune cells in liver tissue. Preliminary analysis of the MSC secretome using a protein array screen revealed a large fraction of chemotactic cytokines, or chemokines. When MSC-CM was fractionated based on heparin binding affinity, a known ligand for all chemokines, only the heparin-bound eluent reversed FHF indicating that the active components of MSC-CM reside in this fraction. These data provide the first experimental evidence of the medicinal use of MSC-derived molecules in the treatment of an inflammatory condition and support the role of chemokines and altered leukocyte migration as a novel therapeutic modality for FHF.

  13. Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Fernando Antonio Fierro

    2015-10-01

    Full Text Available Many therapies using mesenchymal stem cells (MSC rely on their ability to produce and release paracrine signals with chemotactic and pro-angiogenic activity. These characteristics, however, are mostly studied under standard in vitro culture conditions. In contrast, various novel cell-based therapies imply pre-seeding MSC into bio-artificial scaffolds. Here we describe human bone marrow-derived MSC seeded in Integra matrices, a common type of scaffold for dermal regeneration (SDR. We show and measured the distribution of MSC within the SDR, where cells clearly establish physical interactions with the scaffold, exhibiting constant metabolic activity for at least 15 days. In the SDR, MSC secrete VEGF and SDF-1 and induce transwell migration of CD34+ hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1 antagonist. MSC in SDR respond to hypoxia by altering levels of angiogenic signals such as Angiogenin, Serpin-1, uPA and IL-8. Finally, we show that MSC-containing SDR that have been pre-incubated in hypoxia show higher infiltration of endothelial cells after implantation into immune deficient mice. Our data show that MSC are fully functional ex vivo when implanted into SDR. In addition, our results strongly support the notion of hypoxic pre-conditioning MSC-containing SDR, in order to promote angiogenesis in the wounds.

  14. Study of hMSC proliferation and differentiation on Mg and Mg–Sr containing biphasic β-tricalcium phosphate and amorphous calcium phosphate ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Satish S., E-mail: sss42@pitt.edu [Department of Chemical & Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Roy, Abhijit, E-mail: abr20@pitt.edu [Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Lee, Boeun [Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Kumta, Prashant N., E-mail: pkumta@pitt.edu [Department of Chemical & Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Department of Mechanical Engineering and Materials Science, University of Pittsburgh, PA 15261 (United States)

    2016-07-01

    Biphasic mixtures of either Mg{sup 2+} or combined Mg{sup 2+} and Sr{sup 2+} cation substituted β-tricalcium phosphate (β-TCP) and amorphous calcium phosphate (ACP) were prepared using a low temperature chemical phosphatizing and hydrolysis reaction approach. Scaffolds prepared using the cation substituted calcium phosphates were capable of supporting similar levels of human mesenchymal stem cell proliferation in comparison to commercially available β-TCP. The concentrations of Mg{sup 2+}, Sr{sup 2+}, and PO{sub 4}{sup 3−} released from these scaffolds were also within the ranges desired from previous reports to support both hMSC proliferation and osteogenic differentiation. Interestingly, hMSCs cultured directly on scaffolds prepared with only Mg{sup 2+} substituted β-TCP were capable of supporting statistically significantly increased alkaline phosphatase activity, osteopontin, and osteoprotegerin expression in comparison to all compositions containing both Mg{sup 2+} and Sr{sup 2+}, and commercially available β-TCP. hMSCs cultured in the presence of scaffold extracts also exhibited similar trends in the expression of osteogenic markers as was observed during direct culture. Therefore, it was concluded that the enhanced differentiation observed was due to the release of bioactive ions rather than the surface microstructure. The role of these ions on transforming growth factor-β and bone morphogenic protein signaling was also evaluated using a PCR array. It was concluded that the release of these ions may support enhanced differentiation through SMAD dependent TGF-β and BMP signaling. - Highlights: • Synthesis of Mg and Mg-Sr containing biphasic beta tricalcium phosphate ceramics • Magnesium substitution influences ALP activity compared to strontium content. • Solution extract plays a more dominant role on hMSC differentiation. • Direct and indirect Mg and Mg-Sr TCP culture show similar OPG and OPN expression.

  15. Mechano-growth factor induces migration of rat mesenchymal stem cells by altering its mechanical properties and activating ERK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jiamin; Wu, Kewen; Lin, Feng; Luo, Qing; Yang, Li; Shi, Yisong [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Song, Guanbin, E-mail: song@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Sung, Kuo-Li Paul [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412 (United States)

    2013-11-08

    Highlights: •MGF induced the migration of rat MSC in a concentration-dependent manner. •MGF enhanced the mechanical properties of rMSC in inducing its migration. •MGF activated the ERK 1/2 signaling pathway of rMSC in inducing its migration. •rMSC mechanics may synergy with ERK 1/2 pathway in MGF-induced rMSC migration. -- Abstract: Mechano-growth factor (MGF) generated by cells in response to mechanical stimulation has been identified as a mechano effector molecule, playing a key role in regulating mesenchymal stem cell (MSC) function, including proliferation and migration. However, the mechanism(s) underlying how MGF-induced MSC migration occurs is still unclear. In the present study, MGF motivated migration of rat MSCs (rMSCs) in a concentration-dependent manner and optimal concentration of MGF at 50 ng/mL (defined as MGF treatment in this paper) was demonstrated. Notably, enhancement of mechanical properties that is pertinent to cell migration, such as cell traction force and cell stiffness were found to respond to MGF treatment. Furthermore, MGF increased phosphorylation of extracellular signal-regulated kinase (ERK), ERK inhibitor (i.e., PD98059) suppressed ERK phosphorylation, and abolished MGF-induced rMSC migration were found, demonstrating that ERK is involved molecule for MGF-induced rMSC migration. These in vitro evidences of MGF-induced rMSC migration and its direct link to altering rMSC mechanics and activating the ERK pathway, uncover the underlying biomechanical and biological mechanisms of MGF-induced rMSC migration, which may help find MGF-based application of MSC in clinical therapeutics.

  16. Analysis of SMA Hybrid Composite Structures in MSC.Nastran and ABAQUS

    Science.gov (United States)

    Turner, Travis L.; Patel, Hemant D.

    2005-01-01

    A thermoelastic constitutive model for shape memory alloy (SMA) actuators and SMA hybrid composite (SMAHC) structures was recently implemented in the commercial finite element codes MSC.Nastran and ABAQUS. The model may be easily implemented in any code that has the capability for analysis of laminated composite structures with temperature dependent material properties. The model is also relatively easy to use and requires input of only fundamental engineering properties. A brief description of the model is presented, followed by discussion of implementation and usage in the commercial codes. Results are presented from static and dynamic analysis of SMAHC beams of two types; a beam clamped at each end and a cantilever beam. Nonlinear static (post-buckling) and random response analyses are demonstrated for the first specimen. Static deflection (shape) control is demonstrated for the cantilever beam. Approaches for modeling SMAHC material systems with embedded SMA in ribbon and small round wire product forms are demonstrated and compared. The results from the commercial codes are compared to those from a research code as validation of the commercial implementations; excellent correlation is achieved in all cases.

  17. Evaluation of different Project Based Learning designs in an MSc degree

    Directory of Open Access Journals (Sweden)

    Carmen García Berdonés

    2014-03-01

    Full Text Available The design and implementation of different Project Based Learning (PBL approaches are presented in this paper. All of them were carried out in the framework of the MSc degree in Electronic Systems for Smart Environments from the University of Malaga. Four subjects were developed using different values of the three main parameters of PBL: teamwork, self-guided learning and project complexity. During two academic years, several indicators were used to evaluate these experiences: compliance with subject time schedules, scores obtained for the students, interaction of each student in his team and satisfaction of students with the experiences. Our results encourage the use of PBL in bachelor degrees but, at the same time, confirm that PBL implementation is not a trivial task when projects are complex or when a high level of autonomous learning is required from students. Teamwork difficulties have also been found. So, we discuss the need of reaching a minimum level of proficiency in some key competencies before using PBL.

  18. Transient analysis mode participation for modal survey target mode selection using MSC/NASTRAN DMAP

    Science.gov (United States)

    Barnett, Alan R.; Ibrahim, Omar M.; Sullivan, Timothy L.; Goodnight, Thomas W.

    1994-01-01

    Many methods have been developed to aid analysts in identifying component modes which contribute significantly to component responses. These modes, typically targeted for dynamic model correlation via a modal survey, are known as target modes. Most methods used to identify target modes are based on component global dynamic behavior. It is sometimes unclear if these methods identify all modes contributing to responses important to the analyst. These responses are usually those in areas of hardware design concerns. One method used to check the completeness of target mode sets and identify modes contributing significantly to important component responses is mode participation. With this method, the participation of component modes in dynamic responses is quantified. Those modes which have high participation are likely modal survey target modes. Mode participation is most beneficial when it is used with responses from analyses simulating actual flight events. For spacecraft, these responses are generated via a structural dynamic coupled loads analysis. Using MSC/NASTRAN DMAP, a method has been developed for calculating mode participation based on transient coupled loads analysis results. The algorithm has been implemented to be compatible with an existing coupled loads methodology and has been used successfully to develop a set of modal survey target modes.

  19. Resistance for Genotoxic Damage in Mesenchymal Stromal Cells Is Increased by Hypoxia but Not Generally Dependent on p53-Regulated Cell Cycle Arrest

    Science.gov (United States)

    Wieduwild, Elisabeth; Nerger, Katrin; Lambrecht, Nina; Schmoll, Hans-Joachim; Müller-Tidow, Carsten; Müller, Lutz Peter

    2017-01-01

    Adult stem cells including multipotent mesenchymal stromal cells (MSC) acquire a high amount of DNA-damage due to their prolonged lifespan. MSC may exert specific mechanisms of resistance to avoid loss of functional activity. We have previously shown that resistance of MSC is associated with an induction of p53 and proliferation arrest upon genotoxic damage. Hypoxia may also contribute to resistance in MSC due to the low oxygen tension in the niche. In this study we characterized the role of p53 and contribution of hypoxia in resistance of MSC to genotoxic damage. MSC exhibited increased resistance to cisplatin induced DNA-damage. This resistance was associated with a temporary G2/M cell cycle arrest, induction of p53- and p21-expression and reduced cyclin B / cdk1-levels upon subapoptotic damage. Resistance of MSC to cisplatin was increased at hypoxic conditions i. e. oxygen <0.5%. However, upon hypoxia the cisplatin-induced cell cycle arrest and expression of p53 and p21 were abrogated. MSC with shRNA-mediated p53 knock-down showed a reduced cell cycle arrest and increased cyclin B / cdk1 expression. However, this functional p53 knock down did not alter the resistance to cisplatin. In contrast to cisplatin, functional p53-knock-down increased the resistance of MSC to etoposide. We conclude that resistance of MSC to genotoxic damage is influenced by oxygen tension but is not generally dependent on p53. Thus, p53-dependent and p53-independent mechanisms of resistance are likely to contribute to the life-long functional activity of MSC in vivo. These findings indicate that hypoxia and different resistance pathways contribute to the phenotype that enables the prolonged lifespan of MSC. PMID:28081228

  20. Toward an ideal animal model to trace donor cell fates after stem cell therapy: production of stably labeled multipotent mesenchymal stem cells from bone marrow of transgenic pigs harboring enhanced green fluorescence protein gene.

    Science.gov (United States)

    Hsiao, F S H; Lian, W S; Lin, S P; Lin, C J; Lin, Y S; Cheng, E C H; Liu, C W; Cheng, C C; Cheng, P H; Ding, S T; Lee, K H; Kuo, T F; Cheng, C F; Cheng, W T K; Wu, S C

    2011-11-01

    The discovery of postnatal mesenchymal stem cells (MSC) with their general multipotentiality has fueled much interest in the development of cell-based therapies. Proper identification of transplanted MSC is crucial for evaluating donor cell distribution, differentiation, and migration. Lack of an efficient marker of transplanted MSC has precluded our understanding of MSC-related regenerative studies, especially in large animal models such as pigs. In the present study, we produced transgenic pigs harboring an enhanced green fluorescent protein (EGFP) gene. The pigs provide a reliable and reproducible source for obtaining stable EGFP-labeled MSC, which is very useful for donor cell tracking after transplantation. The undifferentiated EGFP-tagged MSC expressed a greater quantity of EGFP while maintaining MSC multipotentiality. These cells exhibited homogeneous surface epitopes and possessed classic trilineage differentiation potential into osteogenic, adipogenic, and chondrogenic lineages, with robust EGFP expression maintained in all differentiated progeny. Injection of donor MSC can dramatically increase the thickness of infarcted myocardium and improve cardiac function in mice. Moreover, the MSC, with their strong EGFP expression, can be easily distinguished from the background autofluorescence in myocardial infarcts. We demonstrated an efficient, effective, and easy way to identify MSC after long-term culture and transplantation. With the transgenic model, we were able to obtain stem or progenitor cells in earlier passages compared with the transfection of traceable markers into established MSC. Because the integration site of the transgene was the same for all cells, we lessened the potential for positional effects and the heterogeneity of the stem cells. The EGFP-transgenic pigs may serve as useful biomedical and agricultural models of somatic stem cell biology.

  1. Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts.

    Directory of Open Access Journals (Sweden)

    Paola Secchiero

    Full Text Available BACKGROUND: Although multimodality treatment can induce high rate of remission in many subtypes of non-Hodgkin's lymphoma (NHL, significant proportions of patients relapse with incurable disease. The effect of human bone marrow (BM mesenchymal stem cells (MSC on tumor cell growth is controversial, and no specific information is available on the effect of BM-MSC on NHL. METHODOLOGY/PRINCIPAL FINDINGS: The effect of BM-MSC was analyzed in two in vivo models of disseminated non-Hodgkin's lymphomas with an indolent (EBV(- Burkitt-type BJAB, median survival = 46 days and an aggressive (EBV(+ B lymphoblastoid SKW6.4, median survival = 27 days behavior in nude-SCID mice. Intra-peritoneal (i.p. injection of MSC (4 days after i.p. injection of lymphoma cells significantly increased the overall survival at an optimal MSC:lymphoma ratio of 1:10 in both xenograft models (BJAB+MSC, median survival = 58.5 days; SKW6.4+MSC, median survival = 40 days. Upon MSC injection, i.p. tumor masses developed more slowly and, at the histopathological observation, exhibited a massive stromal infiltration coupled to extensive intra-tumor necrosis. In in vitro experiments, we found that: i MSC/lymphoma co-cultures modestly affected lymphoma cell survival and were characterized by increased release of pro-angiogenic cytokines with respect to the MSC, or lymphoma, cultures; ii MSC induce the migration of endothelial cells in transwell assays, but promoted endothelial cell apoptosis in direct MSC/endothelial cell co-cultures. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that BM-MSC exhibit anti-lymphoma activity in two distinct xenograft SCID mouse models of disseminated NHL.

  2. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demouth, Christina; Safwat, Akmal;

    2016-01-01

    growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI....... However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin....

  3. Health Inequities: Evaluation of Two Paradigms

    Science.gov (United States)

    Ashcroft, Rachelle

    2010-01-01

    Social work practice in health is shaped by underlying paradigms. To effectively target health inequities, practitioners need to consider appropriate paradigms. In this exploration of how six health paradigms shape theory and practice, the two health paradigms that most attended to health inequalities are social determinants of health and…

  4. Interfacing Sca-1pos Mesenchymal Stem Cells with Biocompatible Scaffolds with Different Chemical Composition and Geometry

    Directory of Open Access Journals (Sweden)

    G. Forte

    2009-01-01

    Full Text Available An immortalized murine mesenchymal stem cell line (mTERT-MSC enriched for Linneg/Sca-1pos fraction has been obtained through the transfection of MSC with murine TERT and single-cell isolation. Such cell line maintained the typical MSC self-renewal capacity and continuously expressed MSC phenotype. Moreover, mTERT-MSC retained the functional features of freshly isolated MSC in culture without evidence of senescence or spontaneous differentiation events. Thus, mTERT-MSC have been cultured onto PLA films, 30 and 100 μm PLA microbeads, and onto unpressed and pressed HYAFF-11 scaffolds. While the cells adhered preserving their morphology on PLA films, clusters of mTERT-MSC were detected on PLA beads and unpressed fibrous scaffolds. Finally, mTERT-MSC were not able to colonize the inner layers of pressed HYAFF-11. Nevertheless, such cell line displayed the ability to preserve Sca-1 expression and to retain multilineage potential when appropriately stimulated on all the scaffolds tested.

  5. Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Salamon, Achim, E-mail: achim.salamon@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Jonitz-Heincke, Anika, E-mail: anika.jonitz@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Adam, Stefanie, E-mail: stefanie.adam@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Rychly, Joachim, E-mail: joachim.rychly@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Müller-Hilke, Brigitte, E-mail: brigitte.mueller-hilke@med.uni-rostock.de [Institute of Immunology, Rostock University Medical Center, Schillingallee 68, D-18057 Rostock (Germany); Bader, Rainer, E-mail: rainer.bader@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Lochner, Katrin, E-mail: katrin.lochner@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Peters, Kirsten, E-mail: kirsten.peters@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany)

    2013-11-01

    Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, and CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but

  6. Use of a stress-minimisation paradigm in high cell density fed-batch Escherichia coli fermentations to optimise recombinant protein production.

    Science.gov (United States)

    Wyre, Chris; Overton, Tim W

    2014-09-01

    Production of recombinant proteins is an industrially important technique in the biopharmaceutical sector. Many recombinant proteins are problematic to generate in a soluble form in bacteria as they readily form insoluble inclusion bodies. Recombinant protein solubility can be enhanced by minimising stress imposed on bacteria through decreasing growth temperature and the rate of recombinant protein production. In this study, we determined whether these stress-minimisation techniques can be successfully applied to industrially relevant high cell density Escherichia coli fermentations generating a recombinant protein prone to forming inclusion bodies, CheY-GFP. Flow cytometry was used as a routine technique to rapidly determine bacterial productivity and physiology at the single cell level, enabling determination of culture heterogeneity. We show that stress minimisation can be applied to high cell density fermentations (up to a dry cell weight of >70 g L(-1)) using semi-defined media and glucose or glycerol as carbon sources, and using early or late induction of recombinant protein production, to produce high yields (up to 6 g L(-1)) of aggregation-prone recombinant protein in a soluble form. These results clearly demonstrate that stress minimisation is a viable option for the optimisation of high cell density industrial fermentations for the production of high yields of difficult-to-produce recombinant proteins, and present a workflow for the application of stress-minimisation techniques in a variety of fermentation protocols.

  7. The Impact of IBM Cell Technology on the Programming Paradigm in the Context of Computer Systems for Climate and Weather Models

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Shujia; Duffy, Daniel; Clune, Thomas; Suarez, Max; Williams, Samuel; Halem, Milton

    2009-01-10

    The call for ever-increasing model resolutions and physical processes in climate and weather models demands a continual increase in computing power. The IBM Cell processor's order-of-magnitude peak performance increase over conventional processors makes it very attractive to fulfill this requirement. However, the Cell's characteristics, 256KB local memory per SPE and the new low-level communication mechanism, make it very challenging to port an application. As a trial, we selected the solar radiation component of the NASA GEOS-5 climate model, which: (1) is representative of column physics components (half the total computational time), (2) has an extremely high computational intensity: the ratio of computational load to main memory transfers, and (3) exhibits embarrassingly parallel column computations. In this paper, we converted the baseline code (single-precision Fortran) to C and ported it to an IBM BladeCenter QS20. For performance, we manually SIMDize four independent columns and include several unrolling optimizations. Our results show that when compared with the baseline implementation running on one core of Intel's Xeon Woodcrest, Dempsey, and Itanium2, the Cell is approximately 8.8x, 11.6x, and 12.8x faster, respectively. Our preliminary analysis shows that the Cell can also accelerate the dynamics component (~;;25percent total computational time). We believe these dramatic performance improvements make the Cell processor very competitive as an accelerator.

  8. Longitudinal Cell Tracking and Simultaneous Monitoring of Tissue Regeneration after Cell Treatment of Natural Tendon Disease by Low-Field Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Dagmar Berner

    2016-01-01

    Full Text Available Treatment of tendon disease with multipotent mesenchymal stromal cells (MSC is a promising option to improve tissue regeneration. To elucidate the mechanisms by which MSC support regeneration, longitudinal tracking of MSC labelled with superparamagnetic iron oxide (SPIO by magnetic resonance imaging (MRI could provide important insight. Nine equine patients suffering from tendon disease were treated with SPIO-labelled or nonlabelled allogeneic umbilical cord-derived MSC by local injection. Labelling of MSC was confirmed by microscopy and MRI. All animals were subjected to clinical, ultrasonographical, and low-field MRI examinations before and directly after MSC application as well as 2, 4, and 8 weeks after MSC application. Hypointense artefacts with characteristically low signal intensity were identified at the site of injection of SPIO-MSC in T1- and T2∗-weighted gradient echo MRI sequences. They were visible in all 7 cases treated with SPIO-MSC directly after injection, but not in the control cases treated with nonlabelled MSC. Furthermore, hypointense artefacts remained traceable within the damaged tendon tissue during the whole follow-up period in 5 out of 7 cases. Tendon healing could be monitored at the same time. Clinical and ultrasonographical findings as well as T2-weighted MRI series indicated a gradual improvement of tendon function and structure.

  9. Tumor Irradiation Increases the Recruitment of Circulating Mesenchymal Stem Cells into the Tumor Microenvironment

    Science.gov (United States)

    Klopp, Ann H.; Spaeth, Erika L.; Dembinski, Jennifer L.; Woodward, Wendy A.; Munshi, Anupama; Meyn, Raymond E.; Cox, James D.; Andreeff, Michael; Marini, Frank C.

    2011-01-01

    Mesenchymal stem cells (MSC) migrate to and proliferate within sites of inflammation and tumors as part of the tissue remodeling process. Radiation increases the expression of inflammatory mediators that could enhance the recruitment of MSC into the tumor microenvironment. To investigate this, bilateral murine 4T1 breast carcinomas (expressing renilla luciferase) were irradiated unilaterally (1 or 2 Gy). Twenty-four hours later, 2 × 105 MSC-expressing firefly luciferase were injected i.v. Mice were then monitored with bioluminescent imaging for expression of both renilla (tumor) and firefly (MSC) luciferase. Forty-eight hours postirradiation, levels of MSC engraftment were 34% higher in tumors receiving 2 Gy (P = 0.004) than in the contralateral unirradiated limb. Immunohistochemical staining of tumor sections from mice treated unilaterally with 2 Gy revealed higher levels of MSC in the parenchyma of radiated tumors, whereas a higher proportion of MSC remained vasculature-associated in unirradiated tumors. To discern the potential mediators involved in MSC attraction, in vitro migration assays showed a 50% to 80% increase in MSC migration towards conditioned media from 1 to 5 Gy-irradiated 4T1 cells compared with unirradiated 4T1 cells. Irradiated 4T1 cells had increased expression of the cytokines, transforming growth factor-β1, vascular endothelial growth factor, and platelet-derived growth factor-BB, and this up-regulation was confirmed by immunohistochemistry in tumors irradiated in vivo. Interestingly, the chemokine receptor CCR2 was found to be up-regulated in MSC exposed to irradiated tumor cells and inhibition of CCR2 led to a marked decrease of MSC migration in vitro. In conclusion, clinically relevant low doses of irradiation increase the tropism for and engraftment of MSC in the tumor microenvironment. PMID:18089798

  10. Isolation and analysis of SSEA-4 positive cells derived from fetal marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    LIU Daqing; PEI Xuetao; YANG Yinxiang; GAO Yanhong; YUAN Hongfeng; QIN Lipeng; WANG Yunfang; NAN Xue; SHI Shuangshuang; YUE Wen

    2006-01-01

    A big issue in stem cell research is to derive prospective totipotential stem cells. In this study, fMSC-SSEA-4 cells expressing SSEA-4 antigen were isolated from fetal marrow masenchymal stem cells (fMSCs) using immunomagnetic bead sorting technique. The totipotent cells were identified and their biological characteristics were further studied. The expression of Oct-4 and SSEA-4, carcino- genicity, and the ability to differentiation of fMSC- SSEA-4 cells were evaluated to verify the totipotent potential. fMSC-SSEA-4 cells were isolated successfully from fMSCs (2.5% among fMSCs), while no obvious differences were seen in morphology, growth curve, cell cycle and immunophenotype, Oct-4 and SSEA-4 expression between fMSC-SSEA-4 cells and fMSCs. fMSC-SSEA-4 cells showed normal diploid chromosome karyotype and no carcinoma was induced after inoculation into nude mice. fMSC- SSEA-4 cells could be induced to fat cells, osteogenic cells and neuron-like cells in vitro with different induced factors. The results indicated that there may be a few totipotent cells among the fMSCs and it may offer the experimental basis for the further study and application of fMSCs.

  11. Cultural Paradigms in Management Sciences

    Directory of Open Access Journals (Sweden)

    Lukasz Sulkowski

    2013-09-01

    Full Text Available Purpose: The purpose of this paper is to present an idea for understanding cultural processes in the organizational discourse from the perspective of four paradigms in management sciences based on the concept of G. Burrell and G. Morgan.Methodology: The author has elaborated a valuable list of structures of the scientifi c theory based on the respective paradigms and has compared cultural paradigms in management sciences. The methodology involves an analysis of classical and recent world literature. Nowadays there is no consensus on the defi nitions, types or research models of organizational culture.Originality: In the literature on the subject we can fi nd many, sometimes contradictory cultural research studies that require further analysis. Precisely because of the diversity and complexity of cultural issues in management sciences a multi-paradigmatic analysis is necessary. The paper presents a proposal for a pluralistic approach to the theory and methodology of cultural studies in management sciences.

  12. MUSICAL LITERACY AND EDUCATIONAL PARADIGMS

    Directory of Open Access Journals (Sweden)

    Alboni Marisa Dudeque Pianovski Vieira

    2016-04-01

    Full Text Available The article presents us contemporary conceptions of musical literacy and its relation to educational paradigmatic issues, thus exposing different types of paradigms and their modifications. The possibility to relate and discuss issues related to these paradigms and to the contributions from different authors to musical literacy issues, characterizing graduates, are also among the objectives of this work. The relevance of these issues is in the few existing debates on the paradigms within music education as well as within the possibility of such a study being able to provide useful material for educators. Of bibliographical and documentary nature, this study is based on the works of Schafer (1992, 1997 and Swanwick (1979, 2003, 2014. The results point to the new trend of musical literacy, with an inclusive commitment, made accessible not only to the student who aims to be a professional musician, but also to people from different social contexts.

  13. [Characteristics of migration of adipose tissue derived mesenchymal stromal cells after co-cultivation with activated monocytes in vitro].

    Science.gov (United States)

    Grigor'eva, O A; Korovina, I V; Gogia, B Sh; Sysoeva, V Iu

    2014-01-01

    Mesenchymal stromal cells (MSC) are considered to be promising tool of regenerative medicine. Migration of MSC toward damaged inflammatory site is essential for physiological tissue reparation. Therefore we studied modifications of migratory features of adipose tissue derived MSC (AT-MSC) after co-cultivation with activated monocytes derived from THP-1 cell line. As a result, we have observed an increased migration rate of AT-MSC in vitro in the absence of chemoattractant gradient as well as toward the gradient of PDGF BB (platelet-derived growth factor BB), which is well known chemoattractant for the cells of mesenchymal origin. Furthermore, the rate of directional AT-MSC migration through fibronectin was also increased. We have established that signaling from PDGFRβ which is activated through binding of integrin receptors with extracellular matrix may be possible way to stimulate cellular migration under simulated inflammatory conditions.

  14. Direct Evidence of Mesenchymal Stem Cell Tropism for Tumor and Wounding Microenvironments using In Vivo Bioluminescence Imaging

    Science.gov (United States)

    Kidd, Shannon; Spaeth, Erika; Dembinski, Jennifer L.; Dietrich, Martin; Watson, Keri; Klopp, Ann; Battula, Lokesh; Weil, Micheal; Andreeff, Michael; Marini, Frank C.

    2014-01-01

    Multipotent mesenchymal stromal/stem cells (MSC) have shown potential clinical utility. However, previous assessments of MSC behavior in recipients have relied on visual detection in host tissue following sacrifice, failing to monitor in vivo MSC dispersion in a single animal and limiting the number of variables that can be observed concurrently. In this study, we utilized noninvasive, in vivo bioluminescent imaging to determine conditions under which MSC selectively engraft in sites of inflammation. MSC modified to express firefly luciferase (MSC-ffLuc) were injected into healthy mice or mice bearing inflammatory insults, and MSC localization was followed with bioluminescent imaging. Inflammatory insults investigated included cutaneous needle-stick and surgical incision wounds, as well as xenogeneic and syngeneic tumors. We also compared tumor models in which MSC were intraveneously or intraperitoneally delivered. Our results demonstrate hMSC-ffLuc systemically delivered to non-tumor bearing animals initially reside in the lungs, then egress to the liver and spleen and decrease in signal over time. However, hMSC in wounded mice engraft and remain detectable only in injured sites. Similarly, in syngeneic and xenogeneic breast carcinoma-bearing mice, bioluminescent detection of systemically delivered MSC revealed persistent, specific co-localization with sites of tumor development. This pattern of tropism was also observed in an ovarian tumor model in which MSC were IP injected. In this study we have identified conditions under which MSC tropism and selective engraftment in sites of inflammation can be monitored by bioluminescent imaging over time. Importantly, these consistent findings were independent of tumor type, immunocompetence and route of MSC delivery. PMID:19650040

  15. THE ISOLATION OF NOVEL MESENCHYMAL STROMAL CELL CHEMOTACTIC FACTORS FROM THE CONDITIONED MEDIUM OF TUMOR CELLS

    Science.gov (United States)

    Lin, Siang-Yo; Yang, Jun; Everett, Allen D.; Clevenger, Charles V.; Koneru, Mythili; Mishra, Pravin J.; Kamen, Barton; Banerjee, Debabrata; Glod, John

    2008-01-01

    Bone marrow-derived mesenchymal stromal cells (MSCs) localize to solid tumors. Defining the signaling mechanisms that regulate this process is important to understanding the role of MSCs in tumor growth. Using a combination of chromatography and electrospray tandem mass spectrometry we have identified novel soluble signaling molecules that induce MSC chemotaxis present in conditioned medium of the breast carcinoma cell line MDA-MB231. Previous work has employed survey strategies using ELISA assay to identify known chemokines that promote MSC chemotaxis. While these studies provide valuable insights into the intercellular signals that impact MSC behavior, many less well-described, but potentially important soluble signaling molecules could be overlooked using these methods. Through the less directed method of column chromatography we have identified novel candidate MSC chemotactic peptides. Two proteins, cyclophilin B and hepatoma-derived growth factor were then further characterized and shown to promote MSC chemotaxis. PMID:18722367

  16. Human fetal mesenchymal stem cells.

    Science.gov (United States)

    O'Donoghue, Keelin; Chan, Jerry

    2006-09-01

    Stem cells have been isolated at all stages of development from the early developing embryo to the post-reproductive adult organism. However, the fetal environment is unique as it is the only time in ontogeny that there is migration of stem cells in large numbers into different organ compartments. While fetal neural and haemopoietic stem cells (HSC) have been well characterised, only recently have mesenchymal stem cells from the human fetus been isolated and evaluated. Our group have characterised in human fetal blood, liver and bone marrow a population of non-haemopoietic, non-endothelial cells with an immunophenotype similar to adult bone marrow-derived mesenchymal stem cells (MSC). These cells, human fetal mesenchymal stem cells (hfMSC), are true multipotent stem cells with greater self-renewal and differentiation capacity than their adult counterparts. They circulate in first trimester fetal blood and have been found to traffic into the maternal circulation, engrafting in bone marrow, where they remain microchimeric for decades after pregnancy. Though fetal microchimerism has been implicated in the pathogenesis of autoimmune disease, the biological role of hfMSC microchimerism is unknown. Potential downstream applications of hfMSC include their use as a target cell for non-invasive pre-natal diagnosis from maternal blood, and for fetal cellular and gene therapy. Using hfMSC in fetal therapy offers the theoretical advantages of avoidance of immune rejection, increased engraftment, and treatment before disease pathology sets in. Aside from allogeneic hfMSC in utero transplantation, the use of autologous hfMSC has been brought a step forward with the development of early blood sampling techniques, efficient viral transduction and clonal expansion. Work is ongoing to determine hfMSC fate post-transplantation in murine models of genetic disease. In this review we will examine what is known about hfMSC biology, as well as discussing areas for future research. The

  17. Intranasal administration of human MSC for ischemic brain injury in the mouse: in vitro and in vivo neuroregenerative functions.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Intranasal treatment with C57BL/6 MSCs reduces lesion volume and improves motor and cognitive behavior in the neonatal hypoxic-ischemic (HI mouse model. In this study, we investigated the potential of human MSCs (hMSCs to treat HI brain injury in the neonatal mouse. Assessing the regenerative capacity of hMSCs is crucial for translation of our knowledge to the clinic. We determined the neuroregenerative potential of hMSCs in vitro and in vivo by intranasal administration 10 d post-HI in neonatal mice. HI was induced in P9 mouse pups. 1×10(6 or 2×10(6 hMSCs were administered intranasally 10 d post-HI. Motor behavior and lesion volume were measured 28 d post-HI. The in vitro capacity of hMSCs to induce differentiation of mouse neural stem cell (mNSC was determined using a transwell co-culture differentiation assay. To determine which chemotactic factors may play a role in mediating migration of MSCs to the lesion, we performed a PCR array on 84 chemotactic factors 10 days following sham-operation, and at 10 and 17 days post-HI. Our results show that 2×10(6 hMSCs decrease lesion volume, improve motor behavior, and reduce scar formation and microglia activity. Moreover, we demonstrate that the differentiation assay reflects the neuroregenerative potential of hMSCs in vivo, as hMSCs induce mNSCs to differentiate into neurons in vitro. We also provide evidence that the chemotactic factor CXCL10 may play an important role in hMSC migration to the lesion site. This is suggested by our finding that CXCL10 is significantly upregulated at 10 days following HI, but not at 17 days after HI, a time when MSCs no longer reach the lesion when given intranasally. The results described in this work also tempt us to contemplate hMSCs not only as a potential treatment option for neonatal encephalopathy, but also for a plethora of degenerative and traumatic injuries of the nervous system.

  18. Exploring Paradigms of Crime Reduction

    DEFF Research Database (Denmark)

    Soothill, Keith; Christoffersen, Mogens N.; Hussain, Azhar

    2010-01-01

    on offenders with first-time convictions for shoplifting (n = 1,989), for burglary (n = 1,324) and for violence (n = 1,901), all four paradigms made a contribution to risk of first-time offending for all three crimes. The counter-factual analysis indicated that a focus on structural issues within a society may......Using Danish registers for a 1980 birth cohort of 29,944 males with parental information and following up these cases for 25 years, the study considers four paradigms of crime reduction (parental child rearing, structural factors around adolescence, locality and individual resources). Focusing...

  19. The synthesis paradigm in genetics.

    Science.gov (United States)

    Rice, William R

    2014-02-01

    Experimental genetics with model organisms and mathematically explicit genetic theory are generally considered to be the major paradigms by which progress in genetics is achieved. Here I argue that this view is incomplete and that pivotal advances in genetics--and other fields of biology--are also made by synthesizing disparate threads of extant information rather than generating new information from experiments or formal theory. Because of the explosive expansion of information in numerous "-omics" data banks, and the fragmentation of genetics into numerous subdisciplines, the importance of the synthesis paradigm will likely expand with time.

  20. Bayesian test and Kuhn's paradigm

    Institute of Scientific and Technical Information of China (English)

    Chen Xiaoping

    2006-01-01

    Kuhn's theory of paradigm reveals a pattern of scientific progress,in which normal science alternates with scientific revolution.But Kuhn underrated too much the function of scientific test in his pattern,because he focuses all his attention on the hypothetico-deductive schema instead of Bayesian schema.This paper employs Bayesian schema to re-examine Kuhn's theory of paradigm,to uncover its logical and rational components,and to illustrate the tensional structure of logic and belief,rationality and irrationality,in the process of scientific revolution.

  1. Transmission pricing: paradigms and methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Shirmohammadi, Dariush [Pacific Gas and Electric Co., San Francisco, CA (United States); Vieira Filho, Xisto; Gorenstin, Boris [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil); Pereira, Mario V.P. [Power System Research, Rio de Janeiro, RJ (Brazil)

    1994-12-31

    In this paper we describe the principles of several paradigms and methodologies for pricing transmission services. The paper outlines some of the main characteristics of these paradigms and methodologies such as where they may be used for best results. Due to their popularity, power flow based MW-mile and short run marginal cost pricing methodologies will be covered in some detail. We conclude the paper with examples of the application of these two pricing methodologies for pricing transmission services in Brazil. (author) 25 refs., 2 tabs.

  2. Paradigms in Physics Education Research

    CERN Document Server

    Robertson, Amy D; McKagan, Sarah B

    2013-01-01

    Physics education research (PER) includes three distinct paradigms: quantitative research, qualitative research, and question-driven research. Quantitative PER seeks reproducible, representative patterns and relationships; human behavior is seen as dictated by lawful (albeit probabilistic) relationships. Qualitative PER seeks to refine and develop theory by linking theory to cases; human action is seen as shaped by the meanings that participants make of their local environments. Question-driven physics education researchers prioritize questions over the pursuit of local meanings or abstract relationships. We illustrate each paradigm with interviews with physics education researchers and examples of published PER.

  3. Adjustment of students to be future researchers: The importance of a systematic literature review methodology for MSc students

    OpenAIRE

    B. Andres; Poler, R.

    2014-01-01

    The systematic literature review is one of the first steps in any research work. However, MSc students present their limitations when begin conducting their own dissertation, mandatory to certificate. These limitations are justified due to students are not completely conscientious of the importance of this previous work along any research. Introducing the literature review process from the very beginning is a key factor to its correct elaboration. Therefore, to initially guide students in thi...

  4. Shifting the paradigm

    DEFF Research Database (Denmark)

    Kiss, Katalin; Brozik, Anna; Kucsma, Nora

    2012-01-01

    ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticuloc......ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from...... reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis...

  5. Effect of human adipose tissue-derived mesenchymal-stem-cell bioactive materials on porcine embryo development.

    Science.gov (United States)

    Park, Hyo-Young; Kim, Eun-Young; Lee, Seung-Eun; Choi, Hyun-Yong; Moon, Jeremiah Jiman; Park, Min-Jee; Son, Yeo-Jin; Lee, Jun-Beom; Jeong, Chang-Jin; Lee, Dong-Sun; Riu, Key-Jung; Park, Se-Pill

    2013-12-01

    Human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) secrete bioactive materials that are beneficial for tissue repair and regeneration. In this study, we characterized human hAT-MSC bioactive material (hAT-MSC-BM), and examined the effect of hAT-MSC-BM on porcine embryo development. hAT-MSC-BM was enriched with several growth factors and cytokines, including fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA), and interleukin 6 (IL6). Among the various concentrations and days of treatment tested, 10% hAT-MSC-BM treatment beginning on culture Day 4 provided the best environment for the in vitro growth of parthenogenetic porcine embryos. While the addition of 10% fetal bovine serum (FBS) increased the hatching rate and the total cell number of parthenogenetic porcine embryos compared with the control and hAT-MSC culture medium group, the best results were from the group cultured with 10% hAT-MSC-BM. Mitochondrial activity was also higher in the 10% hAT-MSC-BM-treated group. Moreover, the relative mRNA expression levels of development and anti-apoptosis genes were significantly higher in the 10% hAT-MSC-BM-treated group than in control, hAT-MSC culture medium, or 10% FBS groups, whereas the transcript abundance of an apoptosis gene was slightly lower. Treatment with 10% hAT-MSC-BM starting on Day 4 also improved the development rate and the total cell number of in vitro-fertilized embryos. This is the first report on the benefits of hAT-MSC-BM in a porcine embryo in vitro culture system. We conclude that hAT-MSC-BM is a new, alternative supplement that can improve the development of porcine embryos during both parthenogenesis and fertilization in vitro.

  6. Applications of Recombinant DNA Technology in Gastrointestinal Medicine and Hepatology: Basic Paradigms of Molecular Cell Biology. Part A: Eukaryotic Gene Structure and DNA Replication

    Directory of Open Access Journals (Sweden)

    Gary E Wild

    2000-01-01

    Full Text Available Progress in the basic sciences of cell and molecular biology has provided an exciting dimension that has translated into clinically relevant information in every medical subspecialty. Importantly, the application of recombinant DNA technology has played a major role in unravelling the intricacies related to the molecular pathophysiology of disease. This series of review articles constitutes a framework for the integration of the database of new information into the core knowledge base of concepts related to the pathogenesis of gastrointestinal disorders and liver disease. The goal of this series of three articles is to review the basic principles of eukaryotic gene expression. The first article examines the role of DNA in directing the flow of genetic information in eukaryotic cells.

  7. Applications of Recombinant Dna Technology in Gastrointestinal Medicine and Hepatology: Basic Paradigms of Molecular Cell Biology. Part B: Eukaryotic Gene Transcription and Post-Transcripional Rna Processing

    Directory of Open Access Journals (Sweden)

    Gary E Wild

    2000-01-01

    Full Text Available The transcription of DNA into RNA is the primary level at which gene expression is controlled in eukaryotic cells. Eukaryotic gene transcription  involves several different RNA polymerases that interact with a host of transcription factors to initiate transcription. Genes that encode proteins are transcribed into messenger RNA (mRNA by RNA polymerase II. Ribosomal RNAs (rRNAs and transfer RNAs (tRNAs are transcribed by RNA polymerase I and III, respectively.  The production of each mRNA in human cells involves complex interactions of proteins (ie, trans-acting factors with specific sequences on the DNA (ie, cis-acting elements. Cis-acting elements are short base sequences adjacent to or within a particular gene. While the regulation of transcription is a pivotal step in the control of gene expression, a variety of molecular events, collectively known as ’RNA processing’  add an additional level of control of gene expression in eukaryotic cells.

  8. Human mesenchymal stem cells: from basic biology to clinical applications

    DEFF Research Database (Denmark)

    Abdallah, B M; Kassem, M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  9. Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer.

    Science.gov (United States)

    Ji, Runbi; Zhang, Bin; Zhang, Xu; Xue, Jianguo; Yuan, Xiao; Yan, Yongmin; Wang, Mei; Zhu, Wei; Qian, Hui; Xu, Wenrong

    2015-08-01

    Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer.

  10. Paradigm Statements of Educational Objectives.

    Science.gov (United States)

    Gray, Peter J.

    Five distinct format categories are used in this study to describe the form of educational objectives: clarity, range, level of abstractness, behavioralness, and observability. These form concepts are used to describe paradigm statements of three kinds of educational objectives: goals, intended learning outcomes, and behavioral evidence. Goals are…

  11. Hypoxia Created Human Mesenchymal Stem Cell Sheet for Prevascularized 3D Tissue Construction.

    Science.gov (United States)

    Zhang, Lijun; Xing, Qi; Qian, Zichen; Tahtinen, Mitchell; Zhang, Zhaoqiang; Shearier, Emily; Qi, Shaohai; Zhao, Feng

    2016-02-01

    3D tissue based on human mesenchymal stem cell (hMSC) sheets offers many interesting opportunities for regenerating multiple types of connective tissues. Prevascularizing hMSC sheets with endothelial cells (ECs) will improve 3D tissue performance by supporting cell survival and accelerating integration with host tissue. It is hypothesized that hypoxia cultured hMSC sheets can promote microvessel network formation and preserve stemness of hMSCs. This study investigates the vascularization of hMSC sheets under different oxygen tensions. It is found that the HN condition, in which hMSC sheets formed under physiological hypoxia (2% O2 ) and then cocultured with ECs under normoxia (20% O2 ), enables longer and more branched microvessel network formation. The observation is corroborated by higher levels of angiogenic factors in coculture medium. Additionally, the hypoxic hMSC sheet is more uniform and less defective, which facilitates fabrication of 3D prevascularized tissue construct by layering the prevascularized hMSC sheets and maturing in rotating wall vessel bioreactor. The hMSCs in the 3D construct still maintain multilineage differentiation ability, which indicates the possible application of the 3D construct for various connective tissues regeneration. These results demonstrate that hypoxia created hMSC sheets benefit the microvessel growth and it is feasible to construct 3D prevascularized tissue construct using the prevascularized hMSC sheets.

  12. Prospectively defined murine mesenchymal stem cells inhibit Klebsiella pneumoniae-induced acute lung injury and improve pneumonia survival

    OpenAIRE

    Hackstein, Holger; Lippitsch, Anne; Krug, Philipp; Schevtschenko, Inna; Kranz, Sabine; Hecker, Matthias; Dietert, Kristina; Achim D Gruber; Bein, Gregor; Brendel, Cornelia; Baal, Nelli

    2015-01-01

    Background Numerous studies have described the immunosuppressive capacity of mesenchymal stem cells (MSC) but these studies use mixtures of heterogeneous progenitor cells for in vitro expansion. Recently, multipotent MSC have been prospectively identified in murine bone marrow (BM) on the basis of PDFGRa+ SCA1+ CD45− TER119− (PαS) expression but the immunomodulatory capacity of these MSC is unknown. Methods We isolated PαS MSC by high-purity FACS sorting of murine BM and after in vitro expans...

  13. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients.

    Science.gov (United States)

    Zhang, Zheng; Lin, Hu; Shi, Ming; Xu, Ruonan; Fu, Junliang; Lv, Jiyun; Chen, Liming; Lv, Sa; Li, Yuanyuan; Yu, Shuangjie; Geng, Hua; Jin, Lei; Lau, George K K; Wang, Fu-Sheng

    2012-03-01

    Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC.

  14. [Recent Advances on the Immunoregulation of MicroRNA-155 in Mesenchymal Stem Cells--Review].

    Science.gov (United States)

    Han, Xiao; Wang, Lei; Wu, Tao; Bai, Hai

    2016-02-01

    Mesenchymal stem cells (MSC) are capable of immunosuppression and differentiating into multiple cell lineages. MSC, which are accessed easily and less side-effects, have been a source of seed cells in tissue-engineering and cell-therapy. However, the application of MSC are limited by their differentiation of instability and easy aging. MicroRNA-155 (miR-155) is one of microRNA, which has powerful regulatory potential in a wide variety of immune cells through degrading specific mRNA after transcription and inhibiting translation of the target genes. Following the research of miR-155 deeply, it has an indispensable role in the proliferation, differentiation and immunoregulation of MSC. This review discusses the current understandings for the role of miR-155 in MSC.

  15. Treatment paradigms for patients with metastatic non small cell lung cancer (NSCLC, squamous lung cancer: first, second and third-line

    Directory of Open Access Journals (Sweden)

    Abdulaziz eAl Farsi

    2014-06-01

    Full Text Available Historically, the treatment algorithm applied to non small cell lung cancer (NSCLC was the same for all histologic subtypes. However, recent advances in our understanding of the molecular profiles of squamous and non-squamous NSCLC have changed this perspective. Histologic subtype and the presence of specific molecular abnormalities have predictive value for response to and toxicity from therapy, as well as overall survival. For patients with squamous NSCLC, a platinum agent plus gemcitabine, or paclitaxel is recommended as first-line therapy. The role of EGFR monoclonal antibodies is uncertain. Maintenance therapy is not widely recommended, although data exist for the use of erlotinib. The standard recommendation for second-line therapy is docetaxel and erlotinib should be considered as second or third-line therapy. There is ongoing research identifying molecular targets in squamous NSCLC and many agents are in early phase clinical trials. Immunotherapeutic approaches targeting programmed death 1 receptor (PD-1 and its ligand (PD-L1 appear promising.

  16. Do FY antigens act as minor histocompatibility antigens in the graft-versus-host disease paradigm after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation?

    Science.gov (United States)

    Sellami, Mohamed Hichem; Chaabane, Manel; Kaabi, Houda; Torjemane, Lamia; Ladeb, Saloua; Ben Othmane, Tarek; Hmida, Slama

    2012-03-01

    FY antigens are candidate minor histocompatibility antigens relevant to renal allograft rejection, but no data have been reported about their role in graft-versus-host disease (GVHD) incidence after human leukocyte antigen (HLA)-identical siblings hematopoietic stem cell transplantation (HSCT). The aim of this study was to examine the effect of donor/recipient disparity at FY antigens on the incidence of GVHD in Tunisian patients receiving an HLA-identical HSCT. This work enrolled 105 Tunisian pairs of recipients and their HLA-identical sibling donors of HSCs. FY genotyping was performed with the polymerase chain reaction-sequence-specific primer method and donor/recipient disparity for these antigens was analyzed at two levels: incompatibility and nonidentity. The case-control analyses showed no significant correlation between FY disparity and the incidence of either acute or chronic GVHD. Sample size calculation showed that 572 cases and 1716 controls would be necessary to be able to detect a significant association with 80% power and two-sided type I error level of 5% (α=0.05). The lack of association in the studied cohort may be explained by the low immunogenicity of FY antigens in HSCT context, compared with other antigens such as HA-1 and CD31.

  17. Cardiomyocyte protection by GATA-4 gene engineered mesenchymal stem cells is partially mediated by translocation of miR-221 in microvesicles.

    Directory of Open Access Journals (Sweden)

    Bin Yu

    Full Text Available INTRODUCTION: microRNAs (miRs, a novel class of small non-coding RNAs, are involved in cell proliferation, differentiation, development, and death. In this study, we found that miR-221 translocation by microvesicles (MVs plays an important role in cardioprotection mediated by GATA-4 overexpressed mesenchymal stem cells (MSC. METHODS AND RESULTS: Adult rat bone marrow MSC and neonatal rat ventricle cardiomyocytes (CM were harvested as primary cultures. MSC were transduced with GATA-4 (MSC(GATA-4 using the murine stem cell virus (pMSCV retroviral expression system. Empty vector transfection was used as a control (MSC(Null. The expression of miRs was assessed by real-time PCR and localized using in situ hybridization (ISH. MVs collected from MSC cultures were characterized by expression of CD9, CD63, and HSP70, and photographed with electron microscopy. Cardioprotection during hypoxia afforded by conditioned medium (CdM from MSC cultures was evaluated by lactate dehydrogenase (LDH release, MTS uptake by CM, and caspase 3/7 activity. Expression of miR-221/222 was significantly higher in MSC than in CM and miR-221 was upregulated in MSC(GATA-4. MSC overexpression of miR-221 significantly enhanced cardioprotection by reducing the expression of p53 upregulated modulator of apoptosis (PUMA. Moreover, expression of PUMA was significantly decreased in CM co-cultured with MSC. MVs derived from MSC expressed high levels of miR-221, and were internalized quickly by CM as documented in images obtained from a Time-Lapse Imaging System. CONCLUSIONS: Our results demonstrate that cardioprotection by MSC(GATA-4 may be regulated in part by a transfer of anti-apoptotic miRs contained within MVs.

  18. Mitochondrial Transfer via Tunneling Nanotubes is an Important Mechanism by Which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the In Vitro and In Vivo Models of ARDS.

    Science.gov (United States)

    Jackson, Megan V; Morrison, Thomas J; Doherty, Declan F; McAuley, Daniel F; Matthay, Michael A; Kissenpfennig, Adrien; O'Kane, Cecilia M; Krasnodembskaya, Anna D

    2016-08-01

    Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in preclinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the antimicrobial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC antimicrobial effect in the in vivo model of Escherichia coli pneumonia. Furthermore, we showed that MSC administration was associated with enhanced AM phagocytosis in vivo. We showed that direct coculture of MSC with monocyte-derived macrophages enhanced their phagocytic capacity. By fluorescent imaging and flow cytometry we demonstrated extensive mitochondrial transfer from MSC to macrophages which occurred at least partially through tunneling nanotubes (TNT)-like structures. We also detected that lung macrophages readily acquire MSC mitochondria in vivo, and macrophages which are positive for MSC mitochondria display more pronounced phagocytic activity. Finally, partial inhibition of mitochondrial transfer through blockage of TNT formation by MSC resulted in failure to improve macrophage bioenergetics and complete abrogation of the MSC effect on macrophage phagocytosis in vitro and the antimicrobial effect of MSC in vivo. Collectively, this work for the first time demonstrates that mitochondrial transfer from MSC to innate immune cells leads to enhancement in phagocytic activity and reveals an important novel mechanism for the antimicrobial effect of MSC in ARDS. Stem Cells 2016;34:2210-2223.

  19. M-Learning: A New Paradigm of Learning Mathematics in Malaysia

    CERN Document Server

    Mahamad, Saipunidzam; Taib, Shakirah Mohd; 10.5121/ijcsit.2010.2407

    2010-01-01

    M-Learning is a new learning paradigm of the new social structure with mobile and wireless technologies.Smart school is one of the four flagship applications for Multimedia Super Corridor (MSC) under Malaysian government initiative to improve education standard in the country. With the advances of mobile devices technologies, mobile learning could help the government in realizing the initiative. This paper discusses the prospect of implementing mobile learning for primary school students. It indicates significant and challenges and analysis of user perceptions on potential mobile applications through a survey done in primary school context. The authors propose the m-Learning for mathematics by allowing the extension of technology in the traditional classroom in term of learning and teaching.

  20. M-Learning: A New Paradigm of Learning Mathematics in Malaysia

    Directory of Open Access Journals (Sweden)

    Saipunidzam Mahamad

    2010-09-01

    Full Text Available M-Learning is a new learning paradigm of the new social structure with mobile and wireless technologies.Smart school is one of the four flagship applications for Multimedia Super Corridor (MSC underMalaysian government initiative to improve education standard in the country. With the advances ofmobile devices technologies, mobile learning could help the government in realizing the initiative. Thispaper discusses the prospect of implementing mobile learning for primary school students. It indicatessignificant and challenges and analysis of user perceptions on potential mobile applications through asurvey done in primary school context. The authors propose the m-Learning for mathematics by allowingthe extension of technology in the traditional classroom in term of learning and teaching

  1. Partial suppression of the respiratory defect of qrs1/her2 glutamyl-tRNA amidotransferase mutants by overexpression of the mitochondrial pentatricopeptide Msc6p.

    Science.gov (United States)

    Moda, Bruno S; Ferreira-Júnior, José Ribamar; Barros, Mario H

    2016-08-01

    Recently, a large body of evidences indicates the existence in the mitochondrial matrix of foci that contain different proteins involved in mitochondrial RNA metabolism. Some of these proteins have a pentatricopeptide repeat motif that constitutes their RNA-binding structures. Here we report that MSC6, a mitochondrial pentatricopeptide protein of unknown function, is a multi copy suppressor of mutations in QRS1/HER2 a component of the trimeric complex that catalyzes the transamidation of glutamyl-tRNAQ to glutaminyl-tRNAQ. This is an essential step in mitochondrial translation because of the lack of a specific mitochondrial aminoacyl glutaminyl-tRNA synthetase. MSC6 over-expression did not abolish translation of an aberrant variant form of Cox2p detected in QRS1/HER2 mutants, arguing against a suppression mechanism that bypasses Qrs1p function. A slight decrement of the mitochondrial translation capacity as well as diminished growth on respiratory carbon sources media for respiratory activity was observed in the msc6 null mutant. Additionally, the msc6 null mutant did not display any impairment in RNA transcription, processing or turnover. We concluded that Msc6p is a mitochondrial matrix protein and further studies are required to indicate the specific function of Msc6p in mitochondrial translation.

  2. MSC Adams在双前桥转向机构设计中的应用%Application of MSC Adams in Design of Steering Mechanism of Double-Front Axle

    Institute of Scientific and Technical Information of China (English)

    吕召全; 华从波; 周福庚

    2006-01-01

    本论文对双前桥载货汽车的转向机构进行了全新的设计,在理论计算的基础上利用MSC Adams软件分别对转向梯形和转向摇臂机构进行了运动学仿真,并对其转向特性进行了优化. 随后的道路试验结果表明新设计的转向机构性能符合设计要求.

  3. Understanding the land management paradigm

    DEFF Research Database (Denmark)

    Enemark, Stig

    2006-01-01

    There is a worldwide need to build understanding of the land management paradigm and for institutional development to establish sustainable national concepts. This includes creation and adoption of a policy on land development, and an approach that combines the land administration/cadastre/land r......There is a worldwide need to build understanding of the land management paradigm and for institutional development to establish sustainable national concepts. This includes creation and adoption of a policy on land development, and an approach that combines the land administration....../cadastre/land registration function with topographic mapping. The author seeks to awaken more awareness of global trends in this area, recognising that the systems design involved is always unique....

  4. Explaining (Missing) Regulator Paradigm Shifts

    DEFF Research Database (Denmark)

    Wigger, Angela; Buch-Hansen, Hubert

    2014-01-01

    The global financial and economic crisis has prompted some scholars to suggest that a fundamental regulatory shift away from neoliberalism will take place – both in general and in the field of EU competition regulation. This paper shows that so far no radical break with the neoliberal type...... of competition regulation is heaving into sight. It sets out to explain this from the vantage point of a critical political economy perspective, which identifies the circumstances under which a crisis can result in a regulatory paradigm shift. Contrasting the current situation with the shift in EC/EU competition...... capitalism; the social power configuration underpinning the neoliberal order remains unaltered; no clear counter-project has surfaced; the European Commission has been (and remains) in a position to oppose radical changes; and finally, there are no signs of a wider paradigm shift in the EU's regulatory...

  5. Chemical engineering of mesenchymal stem cells to induce a cell rolling response.

    Science.gov (United States)

    Sarkar, Debanjan; Vemula, Praveen Kumar; Teo, Grace S L; Spelke, Dawn; Karnik, Rohit; Wee, Le Y; Karp, Jeffrey M

    2008-11-19

    Covalently conjugated sialyl Lewis X (SLeX) on the mesenchymal stem cell (MSC) surface through a biotin-streptavidin bridge imparts leukocyte-like rolling characteristics without altering the cell phenotype and the multilineage differentiation potential. We demonstrate that the conjugation of SLeX on the MSC surface is stable, versatile, and induces a robust rolling response on P-selectin coated substrates. These results indicate the potential to increase the targeting efficiency of any cell type to specific tissue.

  6. [Distribution of compact bone mesenchymal stem cells in lung tissue and bone marrow of mouse].

    Science.gov (United States)

    Wang, Rui-Ping; Wu, Ren-Na; Guo, Yu-Qing; Zhang, Bin; Chen, Hu

    2014-02-01

    This study was aimed to investigate the distribution of compact bone mesenchymal stem cells(MSC) marked with lentiviral plasmid pGC FU-RFP-LV in lung tissue and bone marrow of mouse. The MSC were infected by lentivirus with infection efficiency 78%, the infected MSC were injected into BALB/c mice via tail veins in concentration of 1×10(6) /mouse. The mice were randomly divided into 4 group according to 4 time points as 1, 2, 5 and 7 days. The lung tissue and bone marrow were taken and made of frozen sections and smears respectively in order to observed the distributions of MSC. The results indicated that the lentiviral infected MSC displayed phenotypes and biological characteristics which conformed to MSC by immunophenotyping analysis and induction differentiation detection. After the MSC were infected with optimal viral titer MOI = 50, the cell growth no significantly changed; the fluorescent microscopy revealed that the distributions of MSC in bone marrow on day 1, 2, 5 and 7 were 0.50 ± 0.20, 0.67 ± 0.23, 0.53 ± 0.14, 0.33 ± 0.16; those in lung tissue were 0.55 ± 0.15, 0.47 ± 0.13, 0.29 ± 0.13, 0.26 ± 0.08. It is concluded that the distribution of MSC in lung tissue reaches a peak on day 1, while distribution of MSC in bone marrow reaches a peak on day 2. The distribution of mouse MSC relates with RFP gene expression and implantation of MSC in lung tissue and bone marrow.

  7. [Role of Bone Marrow Mesenchymal Stem Cells in Resistance of Chronic Myeloid Leukemia to Tyrosine Kinase Inhibitors -Review].

    Science.gov (United States)

    Zhang, Xiao-Yan; Wan, Qian; Fang, Li-Jun; Li, Jian

    2016-12-01

    Chronic myeloid leukemia (CML) is a disease originated from malignant hematopoietic stem cell disorder. In CML, mesenchymal stem cells(MSC) have been changed in the bone marrow microenvironment, which can protect the leukemia cells from apoptosis induced by tyrosine kinase inhibitors (TKI) and lead to the resistance to TKI by the secretion of soluble factors, involvement in cell-cell adhesion, and so on. This review mainly focuses on the changes of the bone marrow mesenchymal stem cells in CML, as well as the role and mechanism of MSC in the CML resistance of TKI. The concrete probrems dicussing in this review are role of MSC in bone marrow microenviroment, characteristics of MSC in CML, the related mechanisms of MSC in drug resistance and so on.

  8. Employee discipline: a changing paradigm.

    Science.gov (United States)

    Raper, J L; Myaya, S N

    1993-12-01

    To increase the receptiveness of health care supervisors to a broader meaning of discipline and to simulate investigation of nontraditional methods of encouragement to employees who fail to meet minimum standards of conduct and thereby negatively affect the quality of patient care, a subjectively realistic view of the implications of the traditional punitive disciplinary paradigm is presented. Through the use of a case study, the authors present, explain, and apply the contemporary concept of discipline without punishment as first described by J. Huberman.

  9. Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Sassoli, Chiara; Nosi, Daniele; Tani, Alessia; Chellini, Flaminia [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Mazzanti, Benedetta [Dept. of Experimental and Clinical Medicine—Section of Haematology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Quercioli, Franco [CNR-National Institute of Optics (INO), Largo Enrico Fermi 6, 50125 Arcetri-Florence (Italy); Zecchi-Orlandini, Sandra [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Formigli, Lucia, E-mail: formigli@unifi.it [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy)

    2014-05-01

    Recent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the single muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7{sup +} satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration. - Highlights: • MSC-CM contains paracrine factors that up-regulate MMP expression and function in different skeletal muscle cells. • MSC-CM promotes myoblast and satellite cell migration, proliferation and differentiation. • MSC-CM negatively interferes with fibroblast-myoblast transition in primary skeletal fibroblasts. • Paracrine factors from MSCs modulate the fibrotic response and improve the endogenous mechanisms of muscle regeneration.

  10. The Afrocentric Paradigm: Contours and Definitions.

    Science.gov (United States)

    Mazama, Ama

    2001-01-01

    Defines and describes Afrocentricity, suggesting that Afrocentricity within the academic context is best understood as a paradigm. Explains how Afrocentricity meets the definition of a paradigm, examining the affective, cognitive, and conative aspects of the Afrocentric paradigm (metaphysical and sociological) and looking at the structural and…

  11. Orphism as a scientific paradigm

    Directory of Open Access Journals (Sweden)

    Biernat Przemyslaw

    2012-01-01

    Full Text Available In my essay I would like to examine current interpretative paradigm, which western scholarship cast on heterogenous and ambiguous data first to create and then to modify the notion of ‘orphism’. In case of paradigms preceding the actual one, the role which ‘orphism’ played in contemporary theories and controversies centered around the question of its significance for emergence of Christianity is well known. That is why in my work I would like to focus on deconstruction of interpretative consensus, elaborated in recent years, which is to be found in such works as Martin West’s The Orphic Poems (1983, Ritual Texts for the Afterlife. Orpheus and the Bacchic Gold Tablets by Fritz Graf and Sarah Iles-Johnston (2007 or monumental Orfeo y la tradición órfica. Un reencuentro (2008 edited by Alberto Bernabé. What is significant, inasmuch as we can write the history of Athenian religion or the history of Hellenistic kings’ worship, we still cannot write the history of orphism. In formulation of all these scholars it is an ahistorical phenomenon, a hidden constant in the sphere of Greek religion, never expressed directly and entirely, but always alluded to y ancient authors. I find difficult to agree with such a statement. The aim of my inquiry is to reveal assumptions of current paradigm, which are hidden in it, but leave a distinct impression on data.

  12. Poverty eradication: a new paradigm.

    Science.gov (United States)

    Pethe, V P

    1998-08-01

    This article offers a new paradigm for eradicating poverty in India. It was assumed incorrectly by Mahatma Gandhi that a good society without mass poverty would follow after independence. India copied Western models of development and developed giant factories, big dams, and megacities. Agriculture did not expand the number of jobs for people. The Western paradigm failed in India because of the false assumption of "trickle down" of income to the masses. The targeted programs to the poor did not directly benefit enough of the poor. Mega-industrialization led to reduced employment and higher skill needs. The model failed mainly because it was a proxy and relied on indirect ways of reaching the poor. The models failed to be adapted to conditions in India. The Swadeshi paradigm is a direct model for addressing mass poverty. Poverty is affected by immediate, intermediate, and ultimate determinants. Poverty begets social and economic problems, such as ignorance, ill health, high fertility, unemployment, and crime. In India and developing countries, mass poverty results from under use of human resources; lack of equal opportunities; and an outdated non-egalitarian social structure, an unjust global economic order, human cruelty, and erosion of ethical values. Indians are squandering their precious resources mimicking Western consumerism. Poverty leads to rapid population growth. People become productive assets with universal literacy, compulsory and free education, health services and sanitation, vocational training, and work ethics. India needs people-oriented policies with less emphasis on capital accumulation.

  13. Comprehensive Characterization of Mesenchymal Stem Cells from Human Placenta and Fetal Membrane and Their Response to Osteoactivin Stimulation

    Directory of Open Access Journals (Sweden)

    C. M. Raynaud

    2012-01-01

    Full Text Available Mesenchymal stem cells (MSCs are the most promising seed cells for cell therapy and can be isolated from various sources of human adult tissues such as bone marrow (BM-MSC and adipose tissue. However, cells from these tissues must be obtained through invasive procedures. We, therefore, characterized MSCs isolated from fresh placenta (Pl-MSC and fetal membrane (Mb-MSC through morphological and fluorescent-activated cell sorting (FACS. MSC frequency is higher in membrane than placenta (2.14%  ± 0.65 versus 15.67%  ± 0.29%. Pl/Mb-MSCs in vitro expansion potential was significantly higher than BM-MSCs. We demonstrated that one of the MSC-specific marker is sufficient for MSC isolation and that culture in specific media is the optimal way for selecting very homogenous MSC population. These MSCs could be differentiated into mesodermal cells expressing cell markers and cytologic staining consistent with mature osteoblasts and adipocytes. Transcriptomic analysis and cytokine arrays demonstrated broad similarity between placenta- and membrane-derived MSCs and only discrete differences with BM-MSCs with enrichment of networks involved in bone differentiation. Pl/Mb-MSCs displayed higher osteogenic differentiation potential than BM-MSC when their response to osteoactivin was evaluated. Fetal-tissue-derived mesenchymal cells may, therefore, be considered as a major source of MSCs to reach clinical scale banking in particular for bone regeneration.

  14. Serial in vivo imaging of the porcine heart after percutaneous, intramyocardially injected 111In-labeled human mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Lyngbaek, Stig; Ripa, Rasmus S; Haack-Sørensen, Mandana;

    2010-01-01

    This pilot trial aimed to investigate the utilization of (111)In-labeling of mesenchymal stromal cells (MSC) for in vivo tracking after intramyocardial transplantation in a xenotransplantation model with gender mismatched cells. Human male MSC were expanded ex vivo and labeled with (111)In...

  15. Serial in vivo imaging of the porcine heart after percutaneous, intramyocardially injected (111)In-labeled human mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Lyngbæk, Stig; Ripa, Rasmus Sejersten; Haack-Sørensen, Mandana;

    2009-01-01

    This pilot trial aimed to investigate the utilization of (111)In-labeling of mesenchymal stromal cells (MSC) for in vivo tracking after intramyocardial transplantation in a xenotransplantation model with gender mismatched cells. Human male MSC were expanded ex vivo and labeled with (111)In...

  16. Long Period Variables: questioning the pulsation paradigm

    CERN Document Server

    Berlioz-Arthaud, Paul

    2016-01-01

    Long period variables, among them Miras, are thought to be pulsating. Under this approach the whole star inflates and deflates along a period that can vary from 100 to 900 days; that pulsation is assumed to produce shock waves on the outer layers of the star that propagate into the atmosphere and could account for the increase in luminosity and the presence of emission lines in the spectra of these stars. However, this paradigm can seriously be questioned from a theoretical point of view. First, in order to maintain a radial pulsation, the spherical symmetry of the star must be preserved: how can it be reconciled with the large convective cells present in these stars? or when close companions are detected? Secondly, how different radial and non-radial pulsation modes of a sphere could be all damped except one radial mode? These problems have no solution and significantly weigh on the pulsation paradigm. Acknowledging this inconsistency, we show that a close companion around these stars could account for the s...

  17. [Effects of human mesenchymal stem cells and fibroblastoid cell line as feeder layers on expansion of umbilical cord blood CD34(+) cells in vitro].

    Science.gov (United States)

    Ma, Li-Jun; Gao, Lei; Zhou, Hong; Qiu, Hui-Ying; Hu, Xiao-Xia; Xie, Lin-Na; Wang, Jian-Min

    2006-10-01

    To investigate the effects of human mesenchymal stem cells (MSC) and human fibroblastoid cell line (HFCL) as feeder layer on expansion of umbilical cord blood CD34(+) cells in vitro, (60)Co gamma-ray irradiated MSC and HFCL were used as feeder layer to expand cord blood CD34(+) cells in culture. The efficiencies of MSC and HFCL on expansion of CD34(+) cells in culture with or without cytokines were compared. The results showed that no matter whether cytokines (rhFL, rhSCF, rhTPO) were added, the proliferation of nucleated cells after expansion for 12 days in HFCL group was statistically higher than that in MSC group, i.e. with cytokines (9797 +/- 361)% vs (7061 +/- 418)%; without cytokines (5305 +/- 354)% vs (1992 +/- 247)%, when the cell numbers at day 0 was accounted as 100%), P 0.05. However, in the presence of cytokines, the propagating rate of MSC group was lower than that of HFCL group (939 +/- 212)% vs (1617 +/- 222)%, P < 0.01. MSC was better than HFCL in maintaining the LTC-IC of UCB CD34(+) cells, i.e. the number of CFU-GM colonies in the fifth week was (129.95 +/- 8.73) /10(5) seeded cells vs (89.81 +/- 10.29) colonies/10(5) cells, P < 0.05; with addition of cytokines, the effect was more obvious, i.e. the number of CFU-GM colonies in the fifth week (192.93 +/- 4.95)/10(5) seeded cells vs (90.47 +/- 14.28) colonies/10(5) seeded cells, P < 0.01. MSC mixed with a certain proportion of HFCL facilitated maintaining the LTC-IC of UCB CD34(+) cells. When the proportion was 4:1, the number of CFU-GM colonies was the highest (186.89 +/- 11.11)/10(5) seeded cells, which was higher than that of both 3:2 group [(138.92 +/- 14.84) colonies/10(5) seeded cells] and MSC only group, i.e. (64.63 +/- 6.11) colonies/10(5) seeded cells, both P < 0.01. It is concluded that HFCL is better than MSC in maintaining the expansion of CD34(+) cells and cytokines can enhance this effect, while MSC are stronger than HFCL in maintaining the LTC-IC of UCB CD34(+) cells in vitro. MSC

  18. Mesenchymal stem cell exosomes.

    Science.gov (United States)

    Lai, Ruenn Chai; Yeo, Ronne Wee Yeh; Lim, Sai Kiang

    2015-04-01

    MSCs are an extensively used cell type in clinical trials today. The initial rationale for their clinical testing was based on their differentiation potential. However, the lack of correlation between functional improvement and cell engraftment or differentiation at the site of injury has led to the proposal that MSCs exert their effects not through their differentiation potential but through their secreted product, more specifically, exosomes, a type of extracellular vesicle. We propose here that MSC exosomes function as an extension of MSC's biological role as tissue stromal support cells. Like their cell source, MSC exosomes help maintain tissue homeostasis for optimal tissue function. They target housekeeping biological processes that operate ubiquitously in all tissues and are critical in maintaining tissue homeostasis, enabling cells to recover critical cellular functions and begin repair and regeneration. This hypothesis provides a rationale for the therapeutic efficacy of MSCs and their secreted exosomes in a wide spectrum of diseases. Here, we give a brief introduction of the biogenesis of MSC exosomes, review their physiological functions and highlight some of their biochemical potential to illustrate how MSC exosomes could restore tissue homeostasis leading to tissue recovery and repair.

  19. Software Realization on the MSC nanoRISC Hardware Platform, for Communication according to the IEC61850 Standard

    Directory of Open Access Journals (Sweden)

    A. V. Kabović

    2015-06-01

    Full Text Available This paper describes software realization and its implementation for the communication, according to the IEC61850 standard, between the module for monitoring teleprotection devices and the control/monitoring server in a power substation. Teleprotection devices have an important role in the transmission of messages for power line section tripping. The software is implemented on the “MSC nanoRISC-S3C2416 MB2” hardware platform type, which belongs to the COM (computer on module systems.

  20. Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies?

    DEFF Research Database (Denmark)

    Lepperdinger, Günter; Brunauer, Regina; Jamnig, Angelika

    2008-01-01

    cells, which have been expanded in vitro in the presence of xenogenic compounds, can hardly be anticipated and methods for the culture and manipulation of "safe" MSC ex vivo are being investigated. During in vitro expansion, stem cells experience a long replicative history and are thus subject to damage...... advancement, which applies human serum platelet lysates as an alternative source for growth factors and essential supplements, allows the unimpaired proliferation of MSC in the absence of animal sera. Here, we present an update regarding cellular senescence of MSC and recent insights concerning potential...

  1. Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Burns, Jorge S; Abdallah, Basem M; Guldberg, Per

    2005-01-01

    Long-term cultures of telomerase-transduced adult human mesenchymal stem cells (hMSC) may evolve spontaneous genetic changes leading to tumorigenicity in immunodeficient mice (e.g., hMSC-TERT20). We wished to clarify whether this unusual phenotype reflected a rare but dominant subpopulation...... or if the stem cell origin allowed most cells to behave as cancer stem cells. Cultures of the hMSC-TERT20 strain at population doubling 440 were highly clonogenic (94%). From 110 single-cell clones expanded by 20 population doublings, 6 underwent detailed comparison. Like the parental population, each clone had...... tumorigenicity correlated with good viability plus capillary morphogenesis on serum starvation and high cyclin D1 expression. Thus, hMSC-TERT20 clones represent cancer stem cells with hierarchical tumorigenicity, providing new models to explore the stem cell hypothesis for cancer....

  2. On Transferring the Geometric Model of Hull Structure from CATIA to MSC .Patran%关于船体几何模型从 CATIA 到 MSC .Patran 的转换

    Institute of Scientific and Technical Information of China (English)

    向林浩

    2014-01-01

    A method is introduced to transfer the geometric model of ship structure from CATIA to MSC .Patran, so as to form the FE model and extract data about properties and group .A model of CATIA for the hull of 300 000 DWT VLCC is trans-fered to MSC.Patran successfully with complete data .It proves that the method is reliable , practicable and suitable for complex plate-beam model of hull structure by practice .%介绍对CATIA几何模型进行规范化处理,利用CATIA CAE划分网格及优化、提取网格属性及分组信息后转换到MSC.Patran中的方法。以1艘30万t超大型油船( VLCC)舱段结构的CATIA几何模型为例,成功进行转换及计算。验证表明:转换后的信息完整,无需二次加工;该方法可操作性和实用性强,且适用于船体结构复杂的板梁模型。

  3. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self......-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number...

  4. Mesenchymal Stem or Stromal Cells from Amnion and Umbilical Cord Tissue and Their Potential for Clinical Applications

    Directory of Open Access Journals (Sweden)

    Heinz Redl

    2012-11-01

    Full Text Available Mesenchymal stem or stromal cells (MSC have proven to offer great promise for cell-based therapies and tissue engineering applications, as these cells are capable of extensive self-renewal and display a multilineage differentiation potential. Furthermore, MSC were shown to exhibit immunomodulatory properties and display supportive functions through parakrine effects. Besides bone marrow (BM, still today the most common source of MSC, these cells were found to be present in a variety of postnatal and extraembryonic tissues and organs as well as in a large variety of fetal tissues. Over the last decade, the human umbilical cord and human amnion have been found to be a rich and valuable source of MSC that is bio-equivalent to BM-MSC. Since these tissues are discarded after birth, the cells are easily accessible without ethical concerns.

  5. Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration.

    Directory of Open Access Journals (Sweden)

    Ralf Gaebel

    Full Text Available The possible different therapeutic efficacy of human mesenchymal stem cells (hMSC derived from umbilical cord blood (CB, adipose tissue (AT or bone marrow (BM for the treatment of myocardial infarction (MI remains unexplored. This study was to assess the regenerative potential of hMSC from different origins and to evaluate the role of CD105 in cardiac regeneration. Male SCID mice underwent LAD-ligation and received the respective cell type (400.000/per animal intramyocardially. Six weeks post infarction, cardiac catheterization showed significant preservation of left ventricular functions in BM and CD105(+-CB treated groups compared to CB and nontreated MI group (MI-C. Cell survival analyzed by quantitative real time PCR for human GAPDH and capillary density measured by immunostaining showed consistent results. Furthermore, cardiac remodeling can be significantly attenuated by BM-hMSC compared to MI-C. Under hypoxic conditions in vitro, remarkably increased extracellular acidification and apoptosis has been detected from CB-hMSC compared to BM and CD105 purified CB-derived hMSC. Our findings suggests that hMSC originating from different sources showed a different healing performance in cardiac regeneration and CD105(+ hMSC exhibited a favorable survival pattern in infarcted hearts, which translates into a more robust preservation of cardiac function.

  6. Hepatic Stellate Cells Support Hematopoiesis and are Liver-Resident Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Claus Kordes

    2013-02-01

    Full Text Available Background/Aims: Hematopoiesis can occur in the liver, when the bone marrow fails to provide an adequate environment for hematopoietic stem cells. Hepatic stellate cells possess characteristics of stem/progenitor cells, but their contribution to hematopoiesis is not known thus far. Methods: Isolated hepatic stellate cells from rats were characterized with respect to molecular markers of bone marrow mesenchymal stem cells (MSC and treated with adipocyte or osteocyte differentiation media. Stellate cells of rats were further co-cultured with murine stem cell antigen-1+ hematopoietic stem cells selected by magnetic cell sorting. The expression of murine hematopoietic stem cell markers was analyzed by mouse specific quantitative PCR during co-culture. Hepatic stellate cells from eGFP+ rats were transplanted into lethally irradiated wild type rats. Results: Desmin-expressing stellate cells were associated with hematopoietic sites in the fetal rat liver. Hepatic stellate cells expressed MSC markers and were able to differentiate into adipocytes and osteocytes in vitro. Stellate cells supported hematopoietic stem/progenitor cells during co-culture similar to bone marrow MSC, but failed to differentiate into blood cell lineages after transplantation. Conclusion: Hepatic stellate cells are liver-resident MSC and can fulfill typical functions of bone marrow MSC such as the differentiation into adipocytes or osteocytes and support of hematopoiesis.

  7. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    Directory of Open Access Journals (Sweden)

    Ninna Aggerholm-Pedersen

    2016-01-01

    Full Text Available Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

  8. [Paradigm shift in bancroftian filariasis].

    Science.gov (United States)

    Dreyer, Gerusa; Mattos, Denise; Figueredo-Silva, José; Norões, Joaquim

    2009-01-01

    The way a particular subject is understood changes over time as a result of scientific research. In most cases, these changes are minor, with limited effect on the overall knowledge on the subject. Sometimes, however, revolutionary changes occur and not only modify the understanding of the subject but open perspectives that can trigger new interpretations and new ways for expansion of scientific knowledge. The studies of Gregor Johann Mendel were a good example. They led to discovery of the laws of inheritance which, in turn, have revolutionized biology and provided the foundation for genetics. In certain situations, changes not only alter ways of thinking, but have practical implications, also improving the quality of life for many people. In his book The Structure of Scientific Revolutions, Thomas Kuhn refers to discontinuities in scientific development as a 'change of paradigm', a term now used in a generic manner to describe a profound changes in our reference points. For lymphatic filariasis the old paradigm stated that Wuchereria bancrofti at the adult stage causes lymphatic vessel obstruction, triggering an inevitable immune response in predisposed individuals and leading to elephantiasis. This has been replaced by a new paradigm, which offers hope that W. bancrofti infection does not necessarily predispose to the disfiguring outward manifestation of lymphatic dysfunction. Repeated secondary bacterial infections (erysipela-like) are now recognized as the most important factor for initiation and progression of chronic lymphedema in individuals living in filariasis-endemic areas. Most inhabitants of endemic communities can prevent and minimize the acute bacterial episodes by regular use of soap and water, the simplest form of hygiene already well known to human beings.

  9. Straightening and sequential buckling of the pore-lining helices define the gating cycle of MscS.

    Science.gov (United States)

    Akitake, Bradley; Anishkin, Andriy; Liu, Naili; Sukharev, Sergei

    2007-12-01

    We describe a mechanism connecting the adaptive behavior of the bacterial mechanosensitive channel MscS to the flexibility of the pore-lining helix TM3. Simulated expansion of the channel structure revealed straightening of a characteristic kink near Gly113 in the open state; return to the closed state produced an alternative kink at Gly121. Patch-clamp experiments showed that higher helical propensity introduced by a G113A mutation prevented inactivation. A similar mutation, G121A, kinetically impeded both closure and inactivation. Duplicating the glycines at each of these sites to increase flexibility produced directly opposite effects. The severely toxic G113A G121A mutation resulted in channels that could not inactivate or close with the release of tension. These data suggest that the open MscS features straight TM3 helices, which act as collapsible 'struts'. Closure and desensitization rely on buckling at Gly121, whereas the crystal-like kink at Gly113 is a feature of the inactivated state.

  10. International Politics: A Desirable Paradigm

    Institute of Scientific and Technical Information of China (English)

    Xia Aiding; Feng Shuai

    2007-01-01

    This article first traces the origin of four concepts: International Politics (IP), International Relations (IR), World Politics (WP) and Global Politics (GP) and discusses the similarities among these four paradigms. It then analyses their application both at home and abroad. Finally, it argues for the desirability of selecting the concept of IP in academic training, thus facilitating practical application of concepts. It asserts that this will not only enhance academic discussion about IP among different Chinese schools of thought, but also help blazing new ideas.

  11. The Paradigm of Distributed Creativity

    DEFF Research Database (Denmark)

    Glaveanu, Vlad Petre

    This presentation aims to focus on and develop the notion of distributed creativity from a cultural psychological perspective. It will start by outlining the need for a cultural psychological paradigm of creative expression and argue that this perspective is primarily concerned with what can...... be called ‘distributed creativity’. Drawing on related literature on distributed cognition (Hutchins, 2000), I will consider here the three inter-related ways in which creative action is distributed: across people, across people and objects, and across time. This particular understanding of creativity...

  12. Psychiatry beyond the current paradigm.

    LENUS (Irish Health Repository)

    Bracken, Pat

    2012-12-01

    A series of editorials in this Journal have argued that psychiatry is in the midst of a crisis. The various solutions proposed would all involve a strengthening of psychiatry\\'s identity as essentially \\'applied neuroscience\\'. Although not discounting the importance of the brain sciences and psychopharmacology, we argue that psychiatry needs to move beyond the dominance of the current, technological paradigm. This would be more in keeping with the evidence about how positive outcomes are achieved and could also serve to foster more meaningful collaboration with the growing service user movement.

  13. Challenging the Service Cost Paradigm.

    Science.gov (United States)

    Seibert, Sandra

    2015-01-01

    Most healthcare organizations are looking to find more efficient and cost-effective ways of delivering service as they are challenged to assume more risk in order to provide timely and cost effective care. Alternative service with an independent service organization or third party may be an easy and rewarding solution. Serious consideration should be given purchase/service cycle and into a lower cost service paradigm designed to provide excellent service tailored to a facility's specific needs. In this article, an evaluation of all service model options is provided, as well as examples including a CT acquisition, pro formas, and program development.

  14. Mesenchymal stromal cells expressing ErbB-2/neu elicit protective antibreast tumor immunity in vivo, which is paradoxically suppressed by IFN-gamma and tumor necrosis factor-alpha priming.

    Science.gov (United States)

    Romieu-Mourez, Raphaëlle; François, Moïra; Abate, Amanda; Boivin, Marie-Noëlle; Birman, Elena; Bailey, Dana; Bramson, Jonathan L; Forner, Kathy; Young, Yoon-Kow; Medin, Jeffrey A; Galipeau, Jacques

    2010-10-15

    It is unknown whether mesenchymal stromal cells (MSC) can regulate immune responses targeting tumor autoantigens of low immunogenicity. We tested here whether immunization with MSC could break immune tolerance towards the ErbB-2/HER-2/neu tumor antigen and the effects of priming with IFN-γ and tumor necrosis factor-α (TNF-α) on this process. BALB/c- and C57BL/6-derived MSC were lentivirally transduced to express a kinase-inactive rat neu mutant (MSC/Neu). Immunization of BALB/c mice with nontreated or IFN-γ-primed allogeneic or syngeneic MSC/Neu induced similar levels of anti-neu antibody titers; however, only syngeneic MSC/Neu induced protective neu-specific CD8(+) T cell responses. Compared to immunization with nontreated or IFN-γ-primed syngeneic MSC/Neu, the number of circulating neu-specific CD8(+) T cells and titers of anti-neu antibodies were observed to be decreased after immunizations with IFN-γ- plus TNF-α-primed MSC/Neu. In addition, syngeneic MSC/Neu seemed more efficient than IFN-γ-primed MSC/Neu at inducing a protective therapeutic antitumor immune response resulting in the regression of transplanted neu-expressing mammary tumor cells. In vitro antigen-presenting cell assays performed with paraformaldehyde-fixed or live MSC showed that priming with IFN-γ plus TNF-α, compared to priming with IFN-γ alone, increased antigen presentation as well as the production of immunosuppressive factors. These data suggest that whereas MSC could effectively serve as antigen-presenting cells to induce immune responses aimed at tumor autoantigens, these functions are critically regulated by IFN-γ and TNF-α.

  15. Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells

    NARCIS (Netherlands)

    M.J. Crop (Meindert); C.C. Baan (Carla); S.S. Korevaar (Sander); J.N.M. IJzermans (Jan); M. Pescatori (Mario); A. Stubbs (Andrew); W.F.J. van IJcken (Wilfred); M.H. Dahlke (Marc); E. Eggenhofer (Elke); W. Weimar (Willem); M.J. Hoogduijn (Martin)

    2010-01-01

    textabstractThere is emerging interest in the application of mesenchymal stem cells (MSC) for the prevention and treatment of autoimmune diseases, graft-versus-host disease and allograft rejection. It is, however, unknown how inflammatory conditions affect phenotype and function of MSC. Adipose tiss

  16. The effect of marrow mesenchymal stem cell transplantation on pulmonary fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    黄坤

    2012-01-01

    Objective To study the possible mechanisms of marrow mesenchymal stem cells(MSC) in therapy of bleomycin(BLM)-induced pulmonary fibrosis in rats. Methods Fifty-four female Wistar rats were randomly divided into a control group,a BLM group and a MSC group. The control group receivel intratracheal normal

  17. Intranasal mesenchymal stem cell treatment for neonatal brain damage : long-term cognitive and sensorimotor improvement

    NARCIS (Netherlands)

    Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; van Bel, Frank; Kas, Martien J H; Kavelaars, Annemieke; Heijnen, Cobi J

    2013-01-01

    Mesenchymal stem cell (MSC) administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI) brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic wi

  18. Comparison of cellular functionality of human mesenchymal stromal cells and PBMC

    DEFF Research Database (Denmark)

    Schmal, H; Niemeyer, P; Roesslein, M;

    2007-01-01

    .7% of MSC expressed the chemokine receptor CCR-1, as shown by FACS analysis. In contrast, PBMC did not express CCR-1 or CCR-2 but did express CXCR-4 (81.9%) and CCR-7 (42.2%). Setum induced the chemotaxis of both cell types, and zymosan activation increased the migration of PBMC but not of MSC...

  19. Sonic hedgehog mediates the proliferation and recruitment of transformed mesenchymal stem cells to the stomach.

    Directory of Open Access Journals (Sweden)

    Jessica M Donnelly

    Full Text Available Studies using Helicobacter-infected mice show that bone marrow-derived mesenchymal stem cells (MSCs can repopulate the gastric epithelium and promote gastric cancer progression. Within the tumor microenvironment of the stomach, pro-inflammatory cytokine interferon-gamma (IFNγ and Sonic hedgehog (Shh are elevated. IFNγ is implicated in tumor proliferation via activation of the Shh signaling pathway in various tissues but whether a similar mechanism exists in the stomach is unknown. We tested the hypothesis that IFNγ drives MSC proliferation and recruitment, a response mediated by Shh signaling. The current study uses transplantation of an in vitro transformed mesenchymal stem cell line (stMSC(vect, that over-expresses hedgehog signaling, in comparison to non-transformed wild-type MSCs (wtMSCs, wtMSCs transfected to over-express Shh (wtMSC(Shh, and stMSCs transduced with lentiviral constructs containing shRNA targeting the Shh gene (stMSC(ShhKO. The effect of IFNγ on MSC proliferation was assessed by cell cycle analysis in vitro using cells treated with recombinant IFNγ (rmIFNγ alone, or in combination with anti-Shh 5E1 antibody, and in vivo using mice transplanted with MSCs treated with PBS or rmIFNγ. In vitro, IFNγ significantly increased MSC proliferation, a response mediated by Shh that was blocked by 5E1 antibody. The MSC population collected from bone marrow of PBS- or IFNγ-treated mice showed that IFNγ significantly increased the percentage of all MSC cell lines in S phase, with the exception of the stMSCs(ShhKO cells. While the MSC cell lines with intact Shh expression were recruited to the gastric mucosa in response to IFNγ, stMSCs(ShhKO were not. Hedgehog signaling is required for MSC proliferation and recruitment to the stomach in response to IFNγ.

  20. Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction.

    Science.gov (United States)

    Parashurama, Natesh; Ahn, Byeong-Cheol; Ziv, Keren; Ito, Ken; Paulmurugan, Ramasamy; Willmann, Jürgen K; Chung, Jaehoon; Ikeno, Fumiaki; Swanson, Julia C; Merk, Denis R; Lyons, Jennifer K; Yerushalmi, David; Teramoto, Tomohiko; Kosuge, Hisanori; Dao, Catherine N; Ray, Pritha; Patel, Manishkumar; Chang, Ya-Fang; Mahmoudi, Morteza; Cohen, Jeff Eric; Goldstone, Andrew Brooks; Habte, Frezghi; Bhaumik, Srabani; Yaghoubi, Shahriar; Robbins, Robert C; Dash, Rajesh; Yang, Phillip C; Brinton, Todd J; Yock, Paul G; McConnell, Michael V; Gambhir, Sanjiv S

    2016-09-01

    Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.

  1. Hypothesis Formation, Paradigms, and Openness

    Directory of Open Access Journals (Sweden)

    Conrad P. Pritscher

    2008-01-01

    Full Text Available A part of hypothesis formation, while necessary for scientific investigation, is beyond direct observation. Powerful hypothesis formation is more than logical and is facilitated by mind­opening. As Percy Bridgeman, Nobel laureate, said, science is: “Nothing more than doing one's damnedest with one's mind, no holds barred.” This paper suggests more open schooling helps generate more open hypothesizing which helps one do one's damnedest with one's mind. It is hypothesized that a more open process of hypothesis formation may help schools and society forge new ways of living and learning so that more people more often can do their damnedest with their mind. This writing does not offer a new paradigm but rather attempts to elaborate on the notion that new paradigms are difficult to form without openness to what was previously quasi­unthinkable. More on these topics and issues is included in the author's Reopening Einstein's Thought: About What Can't Be Learned From Textbooks ­­to be published by Sense Publishers in June 2008.

  2. Good manufacturing practice-compliant animal-free expansion of human bone marrow derived mesenchymal stroma cells in a closed hollow-fiber-based bioreactor.

    Science.gov (United States)

    Nold, Philipp; Brendel, Cornelia; Neubauer, Andreas; Bein, Gregor; Hackstein, Holger

    2013-01-01

    Mesenchymal stroma cells (MSC) are increasingly recognized for various applications of cell-based therapies such as regenerative medicine or immunomodulatory treatment strategies. Standardized large-scale expansions of MSC under good manufacturing practice (GMP)-compliant conditions avoiding animal derived components are mandatory for further evaluation of these novel therapeutic approaches in clinical trials. We applied a novel automated hollow fiber cell expansion system (CES) for in vitro expansion of human bone marrow derived MSC employing a GMP-compliant culture medium with human platelet lysate (HPL). Between 8 and 32 ml primary bone marrow aspirate were loaded into the hollow fiber CES and cultured for 15-27 days. 2-58 million MSC were harvested after primary culture. Further GMP-compliant cultivation of second passage MSC for 13 days led to further 10-20-fold enrichment. Viability, surface antigen expression, differentiation capacity and immunosuppressive function of MSC cultured in the hollow fiber CES were in line with standard criteria for MSC definition. We conclude that MSC can be enriched from primary bone marrow aspirate in a GMP-conform manner within a closed hollow fiber bioreactor and maintain their T lymphocyte inhibitory capacity. Standardized and reliable conditions for large scale MSC expansion pave the way for safe applications in humans in different therapeutic approaches.

  3. Optimizing patient derived mesenchymal stem cells as virus carriers for a Phase I clinical trial in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Mader Emily K

    2013-01-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSC can serve as carriers to deliver oncolytic measles virus (MV to ovarian tumors. In preparation for a clinical trial to use MSC as MV carriers, we obtained cells from ovarian cancer patients and evaluated feasibility and safety of this approach. Methods MSC from adipose tissues of healthy donors (hMSC and nine ovarian cancer patients (ovMSC were characterized for susceptibility to virus infection and tumor homing abilities. Results Adipose tissue (range 0.16-3.96 grams from newly diagnosed and recurrent ovarian cancer patients yielded about 7.41×106 cells at passage 1 (range 4–9 days. Phenotype and doubling times of MSC were similar between ovarian patients and healthy controls. The time to harvest of 3.0×108 cells (clinical dose could be achieved by day 14 (range, 9–17 days. Two of nine samples tested had an abnormal karyotype represented by trisomy 20. Despite receiving up to 1.6×109 MSC/kg, no tumors were seen in SCID beige mice and MSC did not promote the growth of SKOV3 human ovarian cancer cells in mice. The ovMSC migrated towards primary ovarian cancer samples in chemotaxis assays and to ovarian tumors in athymic mice. Using non-invasive SPECT-CT imaging, we saw rapid co-localization, within 5–8 minutes of intraperitoneal administration of MV infected MSC to the ovarian tumors. Importantly, MSC can be pre-infected with MV, stored in liquid nitrogen and thawed on the day of infusion into mice without loss of activity. MV infected MSC, but not virus alone, significantly prolonged the survival of measles immune ovarian cancer bearing animals. Conclusions These studies confirmed the feasibility of using patient derived MSC as carriers for oncolytic MV therapy. We propose an approach where MSC from ovarian cancer patients will be expanded, frozen and validated to ensure compliance with the release criteria. On the treatment day, the cells will be thawed, washed, mixed with virus, briefly

  4. Mesenchymal Stem Cells Respond to Hypoxia by Increasing Diacylglycerols.

    Science.gov (United States)

    Lakatos, Kinga; Kalomoiris, Stefanos; Merkely, Béla; Nolta, Jan A; Fierro, Fernando A

    2016-02-01

    Mesenchymal stem cells (MSC) are currently being tested clinically for a plethora of conditions, with most approaches relying on the secretion of paracrine signals by MSC to modulate the immune system, promote wound healing, and induce angiogenesis. Hypoxia has been shown to affect MSC proliferation, differentiation, survival and secretory profile. Here, we investigate changes in the lipid composition of human bone marrow-derived MSC after exposure to hypoxia. Using mass spectrometry, we compared the lipid profiles of MSC derived from five different donors, cultured for two days in either normoxia (control) or hypoxia (1% oxygen). Hypoxia induced a significant increase of total triglycerides, fatty acids and diacylglycerols (DG). Remarkably, reduction of DG levels using the phosphatidylcholine-specific phospholipase C inhibitor D609 inhibited the secretion of VEGF and Angiopoietin-2, but increased the secretion of interleukin-8, without affecting significantly their respective mRNA levels. Functionally, incubation of MSC in hypoxia with D609 inhibited the potential of the cells to promote migration of human endothelial cells in a wound/scratch assay. Hence, we show that hypoxia induces in MSC an increase of DG that may affect the angiogenic potential of these cells.

  5. Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model

    Science.gov (United States)

    Tanaka, Yuya; Shirasawa, Bungo; Takeuchi, Yuriko; Kawamura, Daichi; Nakamura, Tamami; Samura, Makoto; Nishimoto, Arata; Ueno, Koji; Morikage, Noriyasu; Hosoyama, Tohru; Hamano, Kimikazu

    2016-01-01

    Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts. PMID:27347329

  6. Mesenchymal bone marrow cell therapy in a mouse model of chagas disease. Where do the cells go?

    Directory of Open Access Journals (Sweden)

    Jasmin

    Full Text Available BACKGROUND: Chagas disease, resulting from infection with the parasite Trypanosoma cruzi (T. cruzi, is a major cause of cardiomyopathy in Latin America. Drug therapy for acute and chronic disease is limited. Stem cell therapy with bone marrow mesenchymal cells (MSCs has emerged as a novel therapeutic option for cell death-related heart diseases, but efficacy of MSC has not been tested in Chagas disease. METHODS AND RESULTS: We now report the use of cell-tracking strategies with nanoparticle labeled MSC to investigate migration of transplanted MSC in a murine model of Chagas disease, and correlate MSC biodistribution with glucose metabolism and morphology of heart in chagasic mice by small animal positron emission tomography (microPET. Mice were infected intraperitoneally with trypomastigotes of the Brazil strain of T. cruzi and treated by tail vein injection with MSC one month after infection. MSCs were labeled with near infrared fluorescent nanoparticles and tracked by an in vivo imaging system (IVIS. Our IVIS results two days after transplant revealed that a small, but significant, number of cells migrated to chagasic hearts when compared with control animals, whereas the vast majority of labeled MSC migrated to liver, lungs and spleen. Additionally, the microPET technique demonstrated that therapy with MSC reduced right ventricular dilation, a phenotype of the chagasic mouse model. CONCLUSIONS: We conclude that the beneficial effects of MSC therapy in chagasic mice arise from an indirect action of the cells in the heart rather than a direct action due to incorporation of large numbers of transplanted MSC into working myocardium.

  7. Glioblastoma-dependent differentiation and angiogenic potential of human mesenchymal stem cells in vitro.

    Science.gov (United States)

    Birnbaum, Tobias; Hildebrandt, Jenna; Nuebling, Georg; Sostak, Petra; Straube, Andreas

    2011-10-01

    Tumor angiogenesis is of central importance in the malignancy of glioblastoma multiforme (GBM). As previously shown, human mesenchymal stem cells (hMSC) migrate towards GBM and are incorporated into tumor microvessels. However, phenotype and function of recruited hMSC remain unclear. We evaluated the differentiation and angiogenic potential of hMSC after stimulation with glioblastoma-conditioned medium in vitro. Immunostaining with endothelial, smooth muscle cell and pericyte markers was used to analyze hMSC differentiation in different concentrations of tumor-conditioned medium (CM), and the angiogenic potential was evaluated by matrigel-based tube-formation assay (TFA). Immunofluorescence staining revealed that tumor-conditioned hMSC (CM-hMSC) expressed CD 151, VE-cadherin, desmin, α-smooth muscle actin, nestin, and nerval/glial antigen 2 (NG2) in a CM concentration-dependent manner, whereas no expression of von-Willebrand factor (vWF) and smooth myosin could be detected. These findings are indicative of GBM-dependent differentiation of hMSC into pericyte-like cells, rather than endothelial or smooth muscle cells. Furthermore, TFA of hMSC and CM-hMSC revealed CM-dependent formation of capillary-like networks, which differed substantially from those formed by human endothelial cells (HUVEC), also implying pericyte-like tube formation. These results are indicative of GBM-derived differentiation of hMSC into pericyte-like mural cells, which might contribute to the neovascularization and stabilization of tumor vessels.

  8. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhao

    2015-01-01

    Full Text Available This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC- derived exosomes (hucMSC-exosomes have a protective effect on acute myocardial infarction (AMI. Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein were intravenously administrated immediately following ligation of the left anterior descending (LAD coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells. The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.

  9. Mesenchymal stem cell subpopulations: phenotype, property and therapeutic potential.

    Science.gov (United States)

    Mo, Miaohua; Wang, Shan; Zhou, Ying; Li, Hong; Wu, Yaojiong

    2016-09-01

    Mesenchymal stem cells (MSC) are capable of differentiating into cells of multiple cell lineages and have potent paracrine effects. Due to their easy preparation and low immunogenicity, MSC have emerged as an extremely promising therapeutic agent in regenerative medicine for diverse diseases. However, MSC are heterogeneous with respect to phenotype and function in current isolation and cultivation regimes, which often lead to incomparable experimental results. In addition, there may be specific stem cell subpopulations with definite differentiation capacity toward certain lineages in addition to stem cells with multi-differentiation potential. Recent studies have identified several subsets of MSC which exhibit distinct features and biological activities, and enhanced therapeutic potentials for certain diseases. In this review, we give an overview of these subsets for their phenotypic, biological and functional properties.

  10. Biofabrication: a 21st century manufacturing paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Mironov, V; Trusk, T; Markwald, R [Medical University of South Carolina, Charleston, SC 29425 (United States); Kasyanov, V [Riga Stradins University, Riga (Latvia); Little, S [South Carolina EPSCoR/IDeA Program, Columbia, SC (United States); Swaja, R [South Carolina Bioengineering Alliance, Charleston, SC 29425 (United States)

    2009-06-01

    Biofabrication can be defined as the production of complex living and non-living biological products from raw materials such as living cells, molecules, extracellular matrices, and biomaterials. Cell and developmental biology, biomaterials science, and mechanical engineering are the main disciplines contributing to the emergence of biofabrication technology. The industrial potential of biofabrication technology is far beyond the traditional medically oriented tissue engineering and organ printing and, in the short term, it is essential for developing potentially highly predictive human cell- and tissue-based technologies for drug discovery, drug toxicity, environmental toxicology assays, and complex in vitro models of human development and diseases. In the long term, biofabrication can also contribute to the development of novel biotechnologies for sustainable energy production in the future biofuel industry and dramatically transform traditional animal-based agriculture by inventing 'animal-free' food, leather, and fur products. Thus, the broad spectrum of potential applications and rapidly growing arsenal of biofabrication methods strongly suggests that biofabrication can become a dominant technological platform and new paradigm for 21st century manufacturing. The main objectives of this review are defining biofabrication, outlining the most essential disciplines critical for emergence of this field, analysis of the evolving arsenal of biofabrication technologies and their potential practical applications, as well as a discussion of the common challenges being faced by biofabrication technologies, and the necessary conditions for the development of a global biofabrication research community and commercially successful biofabrication industry. (topical review)

  11. Mesenchymal Stem Cell Therapy in the Treatment of Acute and Chronic Graft versus Host Disease

    Directory of Open Access Journals (Sweden)

    Partow eKebriaei

    2011-07-01

    Full Text Available Mesenchymal stem cells (MSC are a cellular component of the supportive microenvironment (stroma found in the bone marrow, umbilical cord, placenta and adipose tissues. In addition to providing cellular and extracellular cues to support the proliferation and differentiation of cells that comprise functional tissues, MSC also contribute to tissue repair and have immunomodulatory properties. Their ability to modulate immunologic reactions while themselves not provoking immunologic responses from alloreactive T-lymphocytes and/or other effector cells, make MSC a potentially ideal therapeutic agent with which to treat graft versus host disease (GvHD following hematopoietic transplantation. Despite in vitro experiments confirming that MSC suppress mixed lymphocyte reactions (MLR and in vivo evidence from mouse models that show evidence that MSC can ameliorate GvHD, clinical trials to date using MSC to treat GvHD have shown mixed results. Whether this is a consequence of suboptimal timing and dose of administered MSC remains to be clarified. It is clear that immunomodulatory potential of MSC as a cellular therapy for GvHD remains to be realized in the clinic.

  12. PSYCHOLOGICAL PARADIGMS USED IN TEACHING ANALYSIS

    Directory of Open Access Journals (Sweden)

    Sorin CRISTEA

    2015-11-01

    Full Text Available In this article, teaching as a subject of instruction, will be examined in terms of some actual psychological paradigms of communication: structural-expressive, formal-transactional, relational-systemic, and phenomenal-praxis. Reporting these paradigms, thispaper highlights the importance of psychological processes involved in teaching process. Related to various paradigms described, the author demonstrates the importance of addressing teaching from a high level participation in the elaboration of a mutual action.

  13. Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    宋陆茜

    2013-01-01

    Objective To investigate phenotype,cell differentiation and cytogenetic properties of bone marrow(BM) mesenchymal stem cells(MSC)separated from the myelodysplastic syndrome(MDS) patients,and to analyze cytogenetic

  14. New Paradigms For Asteroid Formation

    CERN Document Server

    Johansen, Anders; Cuzzi, Jeffrey N; Morbidelli, Alessandro; Gounelle, Matthieu

    2015-01-01

    Asteroids and meteorites provide key evidence on the formation of planetesimals in the Solar System. Asteroids are traditionally thought to form in a bottom-up process by coagulation within a population of initially km-scale planetesimals. However, new models challenge this idea by demonstrating that asteroids of sizes from 100 to 1000 km can form directly from the gravitational collapse of small particles which have organised themselves in dense filaments and clusters in the turbulent gas. Particles concentrate passively between eddies down to the smallest scales of the turbulent gas flow and inside large-scale pressure bumps and vortices. The streaming instability causes particles to take an active role in the concentration, by piling up in dense filaments whose friction on the gas reduces the radial drift compared to that of isolated particles. In this chapter we review new paradigms for asteroid formation and compare critically against the observed properties of asteroids as well as constraints from meteo...

  15. Emerging Paradigms in Machine Learning

    CERN Document Server

    Jain, Lakhmi; Howlett, Robert

    2013-01-01

    This  book presents fundamental topics and algorithms that form the core of machine learning (ML) research, as well as emerging paradigms in intelligent system design. The  multidisciplinary nature of machine learning makes it a very fascinating and popular area for research.  The book is aiming at students, practitioners and researchers and captures the diversity and richness of the field of machine learning and intelligent systems.  Several chapters are devoted to computational learning models such as granular computing, rough sets and fuzzy sets An account of applications of well-known learning methods in biometrics, computational stylistics, multi-agent systems, spam classification including an extremely well-written survey on Bayesian networks shed light on the strengths and weaknesses of the methods. Practical studies yielding insight into challenging problems such as learning from incomplete and imbalanced data, pattern recognition of stochastic episodic events and on-line mining of non-stationary ...

  16. The Oral Paradigm and Snapchat

    Directory of Open Access Journals (Sweden)

    Oren Soffer

    2016-09-01

    Full Text Available In this short essay, I argue that the ephemeral nature of emerging instant-messaging applications, such as Snapchat, applies an oral paradigm. While online discourse of computer-mediated communication shares many qualities with oral communication, the case of ephemeral applications is unique, as the oral features are already integrated in the application technology design and as orality is often implemented on highly visual products. Snapchat applies technology that fades visual contents as if they were spoken words fading in the air after utterance. Moreover, Snapchat’s promise to delete all messages from its database after they are viewed echoes a key characteristic of primary oral culture: that is, the inability (and in our case, the obligation not to store knowledge. In this, Snapchat demonstrates counter-logic to the contemporary grammar of new media, which is based on information aggregation.

  17. Understanding the land management paradigm

    DEFF Research Database (Denmark)

    Enemark, Stig

    2006-01-01

    structures by identifying an ideal and historically neutral LAS model for: servicing the needs of governments, business and the public; utilising the latest technologies; servicing rights, responsibilities, restrictions and risks in relation to land; and delivering much broader information about sustainable......Land management is the process by which the resources of land are put into good effect. Land management encompasses all activities associated with the management of land and natural resources that are required to achieve sustainable development. Land Administration Systems (LAS) are institutional...... frameworks complicated by the tasks they must perform, by national cultural, political and judicial settings, and by technology. This paper facilitates an overall understanding of the land management paradigm. This paper assists sharing LAS among countries with diverse legal systems and institutional...

  18. Datacubes as a Service Paradigm

    Science.gov (United States)

    Rossi, Angelo Pio; Baumann, Peter

    2016-04-01

    Spatio-temporal data sets often can be represented conveniently through datacubes as a common unifying paradigm. Flexible, scalable services can be offered based on the concept of a datacube query language while hiding the technicalities, thereby allowing user-friendly visual data interaction. One of today's most influential initiatives in Big Geo Data is EarthServer which is paving the way for flexible, scalable datacube services based on innovative NewSQL technology (Fig. 1). Researchers from Europe, the US and recently Australia have teamed up to rigorously materialize the datacube paradigm for Earth Observation, ocean, meteorological, and planetary science. EarthServer has established client and server technology for such spatio-temporal datacubes strictly based on the open datacube standards, OGC WCS and WPCS. The underlying scalable array engine, rasdaman, enables direct interaction, including 3-D visualization, what-if scenarios, common EO data processing, and general analytics on regular and irregular grids. Integration of datacube and metadata retrieval, together with advanced visualization based on NASA WorldWind, are geared towards an effective, user-friendly access and analysis. Conversely, EarthServer is significantly shaping the ISO, OGC, and INSPIRE Big Data standards landscape by being specification editor. Phase 1 of EarthServer has advanced scalable array data¬base technology into 100+ TB services; in phase 2, a federation of Petabyte datacubes is being built in Europe and Australia to perform ad-hoc querying and merging. Phase 1 reviewers have attested rasdaman to "significantly transform the way that scientists in different areas of Earth Science will be able to access and use data in a way that hitherto was not possible". Altogether, these large-scale deployments prove that datacubes are a convenient model for presenting users with a simple, consolidated view on the massive amount of data files gathered - "a cube tells more than a million

  19. Human Bone Marrow Mesenchymal Stem Cell-Derived Hepatocytes Improve the Mouse Liver after Acute Acetaminophen Intoxication by Preventing Progress of Injury

    Directory of Open Access Journals (Sweden)

    Peggy Stock

    2014-04-01

    Full Text Available Mesenchymal stem cells from human bone marrow (hMSC have the potential to differentiate into hepatocyte-like cells in vitro and continue to maintain important hepatocyte functions in vivo after transplantation into host mouse livers. Here, hMSC were differentiated into hepatocyte-like cells in vitro (hMSC-HC and transplanted into livers of immunodeficient Pfp/Rag2−/− mice treated with a sublethal dose of acetaminophen (APAP to induce acute liver injury. APAP induced a time- and dose-dependent damage of perivenous areas of the liver lobule. Serum levels of aspartate aminotransferase (AST increased to similar levels irrespective of hMSC-HC transplantation. Yet, hMSC-HC resided in the damaged perivenous areas of the liver lobules short-term preventing apoptosis and thus progress of organ destruction. Disturbance of metabolic protein expression was lower in the livers receiving hMSC-HC. Seven weeks after APAP treatment, hepatic injury had completely recovered in groups both with and without hMSC-HC. Clusters of transplanted cells appeared predominantly in the periportal portion of the liver lobule and secreted human albumin featuring a prominent quality of differentiated hepatocytes. Thus, hMSC-HC attenuated the inflammatory response and supported liver regeneration after acute injury induced by acetaminophen. They hence may serve as a novel source of hepatocyte-like cells suitable for cell therapy of acute liver diseases.

  20. Intramyocardial Delivery of Mesenchymal Stem Cell-Seeded Hydrogel Preserves Cardiac Function and Attenuates Ventricular Remodeling after Myocardial Infarction

    Science.gov (United States)

    Mathieu, Eva; Lamirault, Guillaume; Toquet, Claire; Lhommet, Pierre; Rederstorff, Emilie; Sourice, Sophie; Biteau, Kevin; Hulin, Philippe; Forest, Virginie; Weiss, Pierre

    2012-01-01

    Background To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC) therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) hydrogel seeded with MSC (MSC+hydrogel) could preserve cardiac function and attenuate left ventricular (LV) remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI). Methodology/Principal Finding Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. Conclusion/Significance These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium. PMID:23284842

  1. Intramyocardial delivery of mesenchymal stem cell-seeded hydrogel preserves cardiac function and attenuates ventricular remodeling after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Eva Mathieu

    Full Text Available BACKGROUND: To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC hydrogel seeded with MSC (MSC+hydrogel could preserve cardiac function and attenuate left ventricular (LV remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDING: Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. CONCLUSION/SIGNIFICANCE: These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium.

  2. Linking metacommunity paradigms to spatial coexistence mechanisms.

    Science.gov (United States)

    Shoemaker, Lauren G; Melbourne, Brett A

    2016-09-01

    Four metacommunity paradigms-usually called neutral, species sorting, mass effects, and patch dynamics, respectively-are widely used for empirical and theoretical studies of spatial community dynamics. The paradigm framework highlights key ecological mechanisms operating in metacommunities, such as dispersal limitation, competition-colonization tradeoffs, or species equivalencies. However, differences in coexistence mechanisms between the paradigms and in situations with combined influences of multiple paradigms are not well understood. Here, we create a common model for competitive metacommunities, with unique parameterizations for each metacommunity paradigm and for scenarios with multiple paradigms operating simultaneously. We derive analytical expressions for the strength of Chesson's spatial coexistence mechanisms and quantify these for each paradigm via simulation. For our model, fitness-density covariance, a concentration effect measuring the importance of intraspecific aggregation of individuals, is the dominant coexistence mechanism in all three niche-based metacommunity paradigms. Increased dispersal between patches erodes intraspecific aggregation, leading to lower coexistence strength in the mass effects paradigm compared to species sorting. Our analysis demonstrates the potential importance of aggregation of individuals (fitness-density covariance) over co-variation in abiotic environments and competition between species (the storage effect), as fitness-density covariance can be stronger than the storage effect and is the sole stabilizing mechanism in the patch dynamics paradigm. As expected, stable coexistence does not occur in the neutral paradigm, which requires species to be equal and emphasizes the role of stochasticity. We show that stochasticity also plays an important role in niche-structured metacommunities by altering coexistence strength. We conclude that Chesson's spatial coexistence mechanisms provide a flexible framework for comparing

  3. In Vivo Osteoinductive Effect and In Vitro Isolation and Cultivation Bone Marrow Mesenchymal Stem Cells

    OpenAIRE

    Redžić, Amira; Smajilagić, Amer; Aljičević, Mufida; Berberović, Ljubomir

    2010-01-01

    Bone marrow contains cell type termed Mesenchymal Stem Cells (MSC), first recognized in bone marrow by a German pathologist, Julius Cohnheim in 1867. That MSCs have potential to differentiate in vitro in to the various cells lines as osteoblast, chondroblast, myoblast and adipoblast cells lines. Aims of our study were to show in vivo capacity of bone marrow MSC to produce bone in surgically created non critical size mandible defects New Zeeland Rabbits, and then in second part of study to iso...

  4. Distribution of mesenchymal stem cells and effects on neuronal survival and axon regeneration after optic nerve crush and cell therapy.

    Directory of Open Access Journals (Sweden)

    Louise Alessandra Mesentier-Louro

    Full Text Available Bone marrow-derived cells have been used in different animal models of neurological diseases. We investigated the therapeutic potential of mesenchymal stem cells (MSC injected into the vitreous body in a model of optic nerve injury. Adult (3-5 months old Lister Hooded rats underwent unilateral optic nerve crush followed by injection of MSC or the vehicle into the vitreous body. Before they were injected, MSC were labeled with a fluorescent dye or with superparamagnetic iron oxide nanoparticles, which allowed us to track the cells in vivo by magnetic resonance imaging. Sixteen and 28 days after injury, the survival of retinal ganglion cells was evaluated by assessing the number of Tuj1- or Brn3a-positive cells in flat-mounted retinas, and optic nerve regeneration was investigated after anterograde labeling of the optic axons with cholera toxin B conjugated to Alexa 488. Transplanted MSC remained in the vitreous body and were found in the eye for several weeks. Cell therapy significantly increased the number of Tuj1- and Brn3a-positive cells in the retina and the number of axons distal to the crush site at 16 and 28 days after optic nerve crush, although the RGC number decreased over time. MSC therapy was associated with an increase in the FGF-2 expression in the retinal ganglion cells layer, suggesting a beneficial outcome mediated by trophic factors. Interleukin-1β expression was also increased by MSC transplantation. In summary, MSC protected RGC and stimulated axon regeneration after optic nerve crush. The long period when the transplanted cells remained in the eye may account for the effect observed. However, further studies are needed to overcome eventually undesirable consequences of MSC transplantation and to potentiate the beneficial ones in order to sustain the neuroprotective effect overtime.

  5. Cardiac Migration of Endogenous Mesenchymal Stromal Cells in Patients with Inflammatory Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Caroline Schmidt-Lucke

    2015-01-01

    Full Text Available Introduction. Mesenchymal stromal cells (MSC have immunomodulatory features. The aim of this study was to investigate the migration and homing potential of endogenous circulating MSC in virus negative inflammatory cardiomyopathy (CMi. Methods. In 29 patients with n=23 or without n=6 CMi undergoing endomyocardial biopsies (EMB, transcardiac gradients (TCGs of circulating MSC were measured by flow cytometry from blood simultaneously sampled from aorta and coronary sinus. The presence of MSC in EMB, cardiac inflammation, and SDF-1α mRNA expression were detected via immunohistochemistry and real-time PCR. Results. MSC defined as CD45−CD34−CD11b−CD73+CD90+ cells accounted for 0.010 [0.0025–0.048]%/peripheral mononuclear cell (PMNC and as CD45−CD34−CD11b−CD73+CD105+ cells for 0.019 [0.0026–0.067]%/PMNC, both with similar counts in patients with or without cardiac inflammation. There was a 29.9% P<0.01 transcardiac reduction of circulating MSC in patients with CMi, correlating with the extent of cardiac inflammation (P<0.05, multivariate analysis. A strong correlation was found between the TCG of circulating MSC and numbers of MSC (CD45−CD34−CD90+CD105+ in EMB (r=-0.73, P<0.005. SDF-1α was the strongest predictor for increased MSC in EMB (P<0.005, multivariate analysis. Conclusions. Endogenous MSC continuously migrate to the heart in patients with CMi triggered by cardiac inflammation.

  6. Cardiac Migration of Endogenous Mesenchymal Stromal Cells in Patients with Inflammatory Cardiomyopathy

    Science.gov (United States)

    Schmidt-Lucke, Caroline; Escher, Felicitas; Van Linthout, Sophie; Kühl, Uwe; Miteva, Kapka; Schultheiss, Heinz-Peter; Tschöpe, Carsten

    2015-01-01

    Introduction. Mesenchymal stromal cells (MSC) have immunomodulatory features. The aim of this study was to investigate the migration and homing potential of endogenous circulating MSC in virus negative inflammatory cardiomyopathy (CMi). Methods. In 29 patients with (n = 23) or without (n = 6) CMi undergoing endomyocardial biopsies (EMB), transcardiac gradients (TCGs) of circulating MSC were measured by flow cytometry from blood simultaneously sampled from aorta and coronary sinus. The presence of MSC in EMB, cardiac inflammation, and SDF-1α mRNA expression were detected via immunohistochemistry and real-time PCR. Results. MSC defined as CD45−CD34−CD11b−CD73+CD90+ cells accounted for 0.010 [0.0025–0.048]%/peripheral mononuclear cell (PMNC) and as CD45−CD34−CD11b−CD73+CD105+ cells for 0.019 [0.0026–0.067]%/PMNC, both with similar counts in patients with or without cardiac inflammation. There was a 29.9% (P < 0.01) transcardiac reduction of circulating MSC in patients with CMi, correlating with the extent of cardiac inflammation (P < 0.05, multivariate analysis). A strong correlation was found between the TCG of circulating MSC and numbers of MSC (CD45−CD34−CD90+CD105+) in EMB (r = −0.73, P < 0.005). SDF-1α was the strongest predictor for increased MSC in EMB (P < 0.005, multivariate analysis). Conclusions. Endogenous MSC continuously migrate to the heart in patients with CMi triggered by cardiac inflammation. PMID:25814787

  7. CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

    DEFF Research Database (Denmark)

    Harkness, Linda; Zaher, Walid; Ditzel, Nicholas;

    2016-01-01

    BACKGROUND: Identification of surface markers for prospective isolation of functionally homogenous populations of human skeletal (stromal, mesenchymal) stem cells (hMSCs) is highly relevant for cell therapy protocols. Thus, we examined the possible use of CD146 to subtype a heterogeneous h......MSC population. METHODS: Using flow cytometry and cell sorting, we isolated two distinct hMSC-CD146(+) and hMSC-CD146(-) cell populations from the telomerized human bone marrow-derived stromal cell line (hMSC-TERT). Cells were examined for differences in their size, shape and texture by using high......-content analysis and additionally for their ability to differentiate toward osteogenesis in vitro and form bone in vivo, and their migrational ability in vivo and in vitro was investigated. RESULTS: In vitro, the two cell populations exhibited similar growth rate and differentiation capacity to osteoblasts...

  8. The Technological Paradigm of Psychological Research

    Science.gov (United States)

    Kvale, Steinar

    1973-01-01

    The experiment in physics has often been pictured as an ideal for the less mature social sciences, especially by positivist philosophy of science. The thesis to be presented here is that the physical experiment as a paradigm for psychology is merely a pretext, a smoke-screen for a more fundamental and concealed technological paradigm for the study…

  9. Holism and Empiricism as Complementary Paradigms.

    Science.gov (United States)

    Kronick, Doreen

    1990-01-01

    In response to Poplin (EC 210 561) and Heshusius (EC 220 916), the paper stresses that holism and empiricism are not dichotomous paradigms and that learning-disabled students require instruction which recognizes individual differences, the meaning inherent in structure and pattern, and accountability consistent with the paradigm being applied. (DB)

  10. Emergence and decline of scientific paradigms

    DEFF Research Database (Denmark)

    Bornholdt, S.; Jensen, Mogens Høgh; Sneppen, Kim

    2011-01-01

    deals with this asymmetry by constraining the ability of agents to return to already abandoned concepts. The model exhibits a fairly regular pattern of global paradigm shifts, where older paradigms are eroded and subsequently replaced by new ones. The model sets the theme for a new class of pattern...

  11. Reforming the Paradigm of American Education.

    Science.gov (United States)

    Leonard, B. Charles; Messner, Phillip E.

    1991-01-01

    The current crisis of U.S. public education cannot be addressed through reforms to the existing paradigm. In fact, the current paradigm is being challenged and shifted bringing in a new perception of the educational process. Because of resistance in the education profession, that change may be variously applied. (JB)

  12. Derfor har vi brug for paradigmer

    DEFF Research Database (Denmark)

    Kragh, Kirsten A. Jeppesen; Schøsler, Lene

    2016-01-01

    Based on previous studies on verbs of perception in French and Ita- lian, this study claims that the notion of paradigm is useful for the understanding of grammatical structure. Our case-study concerns the status of Modern French voir in the paradigms of presentation and of progressivity....

  13. The Three Paradigms of Mass Media Research.

    Science.gov (United States)

    Potter, W. James; And Others

    A study examined the mass media research literature to determine if there was a dominant paradigm in the field. The mass media research published in eight communication journals from 1965 to 1989 was content analyzed to identify paradigm, orientation (focus and theory), data (type, source, and sample), methodology (type and manipulation), and…

  14. The cognitive paradigm and the immunological homunculus.

    Science.gov (United States)

    Cohen, I R

    1992-12-01

    In last month's issue of Immunology Today, Irun Cohen discussed the inadequacies of the clonal selection paradigm and proposed a cognitive paradigm in which preformed internal images guide and restrict the process of clonal activation. Here he clarifies the nature of these internal images, during on concrete examples from the image of infection and the image of self, the immunological homunculus.

  15. Paradigm Lost: The Human Chromosome Story.

    Science.gov (United States)

    Unger, Lawrence; Blystone, Robert V.

    1996-01-01

    Discusses whether the discovery in 1956 that humans have a chromosome number of 46, as opposed to 47 or 48 as previously thought, fits into a paradigm shift of the Kuhnian type. Concludes that Kuhn probably would not have considered the chromosome number shift to be large enough to be a focus for one of his paradigms. (AIM)

  16. Towards a New Paradigm of Moral Personhood

    Science.gov (United States)

    Frimer, Jeremy A.; Walker, Lawrence J.

    2008-01-01

    Moral psychology is between paradigms. Kohlberg's model of moral rationality has proved inadequate in explaining action; yet its augmentation--moral personality--awaits empirical embodiment. This article addresses some critical issues in developing a comprehensive empirical paradigm of moral personhood. Is a first-person or a third-person…

  17. Multi-Composite Bioactive Osteogenic Sponges Featuring Mesenchymal Stem Cells, Platelet-Rich Plasma, Nanoporous Silicon Enclosures, and Peptide Amphiphiles for Rapid Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Dongmei Fan

    2011-06-01

    Full Text Available A novel bioactive sponge was created with a composite of type I collagen sponges or porous poly(e-caprolactone (PCL scaffolds, platelet-rich plasma (PRP, BMP2-loaded nanoporous silicon enclosure (NSE microparticles, mineralizing peptide amphiphiles (PA, and mesenchymal stem cells (MSC. Primary MSC from cortical bone (CB  tissue proved to form more and larger colony units, as well as produce more mineral matrix under osteogenic differentiation, than MSC from bone marrow (BM. Coating pre-treatments were optimized for maximum cell adhesion and mineralization, while a PRP-based gel carrier was created to efficiently deliver and retain MSC and  microparticles within a porous scaffold while simultaneously promoting cell recruitment, proliferation, and angiogenesis. Components and composite sponges were evaluated for osteogenic differentiation in vitro. Osteogenic sponges were loaded with MSC, PRP, PA, and NSE and implanted subcutaneously in rats to evaluate the formation of bone tissue and angiogenesis in vivo. It was found that the combination of a collagen sponge with CB MSC, PRP, PA, and the BMP2-releasing NSE formed the most bone and was most vascularized by four weeks compared to analogous composites featuring BM MSC or PCL or lacking PRP, PA, and NSE. This study indicates that CB MSC should be considered as an alternative to marrow as a source of stem cells, while the PRP-PA cell and microparticle delivery system may be utilized for diverse tissue engineering applications.

  18. Mechanisms of Cdc42-mediated rat MSC differentiation on micro/nano-textured topography.

    Science.gov (United States)

    Li, Guangwen; Song, Yanyan; Shi, Mengqi; Du, Yuanhong; Wang, Wei; Zhang, Yumei

    2017-02-01

    Micro/nano-textured titanium surface topography promotes osteoblast differentiation and the Wnt/β-catenin signaling pathway. However, the response of rat bone mesenchymal stem cells (MSCs) to micro/nano-textured topography, and the underlying mechanisms of its effects, are not well understood. We hypothesized that cell division cycle 42 protein (Cdc42), a key member of the Rho GTPases family, may regulate rat MSCs morphology and osteogenic differentiation by micro/nano-textured topography, and that crosstalk between Cdc42 and Wnt/β-catenin is the underlying mechanism. To confirm the hypothesis, we first tested rat MSCs' morphology, cytoskeleton, and osteogenic differentiation on micro/nano-textured topography. We then examined the cells' Wnt pathway and Cdc42 signaling activity. The results show that micro/nano-textured topography enhances MSCs' osteogenic differentiation. In addition, the cells' morphology and cytoskeletal reorganization were dramatically different on smooth surfaces and micropitted/nanotubular topography. Ligands of the canonical Wnt pathway, as well as accumulation of β-catenin in the nucleus, were up-regulated by micro/nano-textured topography. Cdc42 protein expression was markedly increased under these conditions; conversely, Cdc42 silencing significantly depressed the enhancement of MSCs osteogenic differentiation by micro/nano-textured topography. Moreover, Cdc42si attenuated p-GSK3β activation and resulted in β-catenin cytoplasmic degradation on the micro/nano-textured topography. Our results indicate that Cdc42 is a key modulator of rat MSCs morphology and cytoskeletal reorganization, and that crosstalk between Cdc42 and Wnt/β-catenin signaling though GSK3β regulates MSCs osteogenic differentiation by implant topographical cues.

  19. A New Paradigm for Chemical Engineering?

    DEFF Research Database (Denmark)

    Gani, Rafiqul

    businesses has been observed. There is an increasing trend within the chemical industry to focus on products and the sustainable processes that can make them. Do these changes point to a paradigm shift in chemical engineering as a discipline? Historically, two previous paradigm shifts in chemical engineering...... corresponded to major shifts in chemical engineering as a discipline, which affected not only the education of chemical engineers, but also the development of chemical engineering as a discipline. Has the time come for a new paradigm shift that will prepare the current and future chemical engineering graduates...... to tackle the complex problems facing the chemicals based industries and serve the modern society more efficiently? The lecture will review the current status of chemical engineering as a discipline, the proposals for the third paradigm, the need for such a paradigm shift and related educational issues....

  20. Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiation

    Directory of Open Access Journals (Sweden)

    Windhager Reinhard

    2007-03-01

    Full Text Available Abstract Background Human mesenchymal stem cells (MSC with the capacity to differentiate into osteoblasts provide potential for the development of novel treatment strategies, such as improved healing of large bone defects. However, their low frequency in bone marrow necessitate ex vivo expansion for further clinical application. In this study we asked if MSC are developing in an aberrant or unwanted way during ex vivo long-term cultivation and if artificial cultivation conditions exert any influence on their stem cell maintenance. To address this question we first developed human oligonucleotide microarrays with 30.000 elements and then performed large-scale expression profiling of long-term expanded MSC and MSC during differentiation into osteoblasts. Results The results showed that MSC did not alter their osteogenic differentiation capacity, surface marker profile, and the expression profiles of MSC during expansion. Microarray analysis of MSC during osteogenic differentiation identified three candidate genes for further examination and functional analysis: ID4, CRYAB, and SORT1. Additionally, we were able to reconstruct the three developmental phases during osteoblast differentiation: proliferation, matrix maturation, and mineralization, and illustrate the activation of the SMAD signaling pathways by TGF-β2 and BMPs. Conclusion With a variety of assays we could show that MSC represent a cell population which can be expanded for therapeutic applications.

  1. The Physical and Cognitive Paradigms in Information Retrieval Research.

    Science.gov (United States)

    Ellis, David

    1992-01-01

    Explores the role of paradigms in information retrieval research and discusses the nature of a paradigm and the applicability of the paradigm concept to a multidisciplinary field such as information science. The features of the physical paradigm and the cognitive paradigm are outlined, and their origins, nature, and role are examined. (55…

  2. Isolation of mesenchymal stem cells from human bone and long-term cultivation under physiologic oxygen conditions.

    Science.gov (United States)

    Klepsch, Sebastian; Jamnig, Angelika; Trimmel, Daniela; Schimke, Magdalena; Kapferer, Werner; Brunauer, Regina; Singh, Sarvpreet; Reitinger, Stephan; Lepperdinger, Günter

    2013-01-01

    Bone-derived stroma cells contain a rare subpopulation, which exhibits enhanced stemness characteristics. Therefore, this particular cell type is often attributed the mesenchymal stem cell (MSC). Due to their high proliferation potential, multipotential differentiation capacity, and immunosuppressive properties, MSCs are now widely appreciated for cell therapeutic applications in a multitude of clinical aspects. In line with this, maintenance of MSC stemness during isolation and culture expansion is considered pivot. Here, we provide step-by-step protocols which allow selection for, and in vitro propagation of high quality MSC from human bone.

  3. Efficient generation of multipotent mesenchymal stem cells from umbilical cord blood in stroma-free liquid culture.

    Directory of Open Access Journals (Sweden)

    Rowayda Peters

    Full Text Available BACKGROUND: Haematopoiesis is sustained by haematopoietic (HSC and mesenchymal stem cells (MSC. HSC are the precursors for blood cells, whereas marrow, stroma, bone, cartilage, muscle and connective tissues derive from MSC. The generation of MSC from umbilical cord blood (UCB is possible, but with low and unpredictable success. Here we describe a novel, robust stroma-free dual cell culture system for long-term expansion of primitive UCB-derived MSC. METHODS AND FINDINGS: UCB-derived mononuclear cells (MNC or selected CD34(+ cells were grown in liquid culture in the presence of serum and cytokines. Out of 32 different culture conditions that have been tested for the efficient expansion of HSC, we identified one condition (DMEM, pooled human AB serum, Flt-3 ligand, SCF, MGDF and IL-6; further denoted as D7 which, besides supporting HSC expansion, successfully enabled long-term expansion of stromal/MSC from 8 out of 8 UCB units (5 MNC-derived and 3 CD34(+ selected cells. Expanded MSC displayed a fibroblast-like morphology, expressed several stromal/MSC-related antigens (CD105, CD73, CD29, CD44, CD133 and Nestin but were negative for haematopoietic cell markers (CD45, CD34 and CD14. MSC stemness phenotype and their differentiation capacity in vitro before and after high dilution were preserved throughout long-term culture. Even at passage 24 cells remained Nestin(+, CD133(+ and >95% were positive for CD105, CD73, CD29 and CD44 with the capacity to differentiate into mesodermal lineages. Similarly we show that UCB derived MSC express pluripotency stem cell markers despite differences in cell confluency and culture passages. Further, we generated MSC from peripheral blood (PB MNC of 8 healthy volunteers. In all cases, the resulting MSC expressed MSC-related antigens and showed the capacity to form CFU-F colonies. CONCLUSIONS: This novel stroma-free liquid culture overcomes the existing limitation in obtaining MSC from UCB and PB enabling so far unmet

  4. MDMA and the "ecstasy paradigm".

    Science.gov (United States)

    Cole, Jon C

    2014-01-01

    For nearly 30 years, there has been a steady flow of research papers highlighting the dangers of MDMA and the implications for ecstasy users. After such a long time, it would be reasonable to expect that these dangers would be obvious due to the large number of ecstasy users. The available evidence does not indicate that there are millions of ecstasy users experiencing any problems linked to their ecstasy use. The "precautionary principle" suggests that, in the absence of knowing for certain, "experts" should argue that MDMA be avoided. However, this may have been taken too far, as the dire warnings do not seem to be reducing with the lack of epidemiological evidence of clinically relevant problems. The "ecstasy paradigm" is one way of articulating this situation, in that the needs of research funders and publication bias lead to a specific set of subcultural norms around what information is acceptable in the public domain. By digging a little deeper, it is easy to find problems with the evidence base that informs the public debate around MDMA. The key question is whether it is acceptable to maintain this status quo given the therapeutic potential of MDMA.

  5. Human Amebiasis: Breaking the Paradigm?

    Directory of Open Access Journals (Sweden)

    Oswaldo Partida

    2010-03-01

    Full Text Available For over 30 years it has been established that the Entamoeba histolytica protozoan included two biologically and genetically different species, one with a pathogenic phenotype called E. histolytica and the other with a non-pathogenic phenotype called Entamoeba dispar. Both of these amoebae species can infect humans. E. histolytica has been considered as a potential pathogen that can cause serious damage to the large intestine (colitis, dysentery and other extraintestinal organs, mainly the liver (amebic liver abscess, whereas E. dispar is a species that interacts with humans in a commensal relationship, causing no symptoms or any tissue damage. This paradigm, however, should be reconsidered or re-evaluated. In the present work, we report the detection and genotyping of E. dispar sequences of DNA obtained from patients with amebic liver abscesses, including the genotyping of an isolate obtained from a Brazilian patient with a clinical diagnosis of intestinal amebiasis that was previously characterized as an E. dispar species. The genetic diversity and phylogenetic analysis performed by our group has shown the existence of several different genotypes of E. dispar that can be associated to, or be potentiality responsible for intestinal or liver tissue damage, similar to that observed with E. histolytica.

  6. A handy new design paradigm

    Directory of Open Access Journals (Sweden)

    B. Bergelin

    2011-02-01

    Full Text Available In light of technological advances, researchers have lost sight of robotic grippers/end effectors design intent. In a semi-structured environment the biomimetic approach is impractical due to the high complexity of the mechanism and control algorithms. Current industrial grippers are robust, but lack the flexibility that allows for in hand manipulation. The authors believe that underactuated grippers provide the best approach to allow for in hand manipulation along with being rugged enough for an industrial setting. Thinking of the robotic gripper and the robotic arm as one system (as opposed to two separate subsystems, one is capable of using the degrees of freedom of the robot in conjunction with that of the gripper to provide the desired motion profile without the complexity of running two subsystems. This paper will outline where recent grippers have failed and will introduce a new design paradigm for grippers along with several underactuated gripper ideas.

    This paper was presented at the IFToMM/ASME International Workshop on Underactuated Grasping (UG2010, 19 August 2010, Montréal, Canada.

  7. Metacognition: A new cognitive paradigm

    Directory of Open Access Journals (Sweden)

    Kankaraš Miloš

    2004-01-01

    Full Text Available This article reviews concept of metacognition, defined as: (a knowledge about ones own cognitive activity, (b strategies to monitor and regulate cognitive activity and behavior, and (c subjective or metacognitive experiences which comes from some changes or temporary difficulties in cognitive functioning. While describing different conceptualizations of metacognition, its development, fields of application, relation with intelligence, and its constrictions and ambiguity, we attempt to present new and emerging metacognitive paradigm, which is, for a relatively short period, succeeded to improve, expand, and redefine wide range of theoretical and practical fields in psychology, on new and original way. How do we become conscious of our own cognitive processes? What role and significance that consciousness has, what is the functional level above thinking processes and how that level, which monitor and control cognitive activity, works. Metacognition is concept that presents, as so far, the most important insight in those human mind areas, which, although very important, remained on the margin of psychological investigations until now.

  8. New Indivisible Planetary Science Paradigm

    CERN Document Server

    Herndon, J Marvin

    2013-01-01

    I present here a new, indivisible planetary science paradigm, a wholly self-consistent vision of the nature of matter in the Solar System, and dynamics and energy sources of planets. Massive-core planets formed by condensing and raining-out from within giant gaseous protoplanets at high pressures and high temperatures. Earth's complete condensation included a 300 Earth-mass gigantic gas/ice shell that compressed the rocky kernel to about 66% of Earth's present diameter. T-Tauri eruptions stripped the gases away from the inner planets and stripped a portion of Mercury's incompletely condensed protoplanet, and transported it to the region between Mars and Jupiter where it fused with in-falling oxidized condensate from the outer regions of the Solar System and formed the parent matter of ordinary chondrite meteorites, the main-Belt asteroids, and veneer for the inner planets, especially Mars. In response to decompression-driven planetary volume increases, cracks form to increase surface area and mountain ranges ...

  9. Macrophage interactions with polylactic acid and chitosan scaffolds lead to improved recruitment of human mesenchymal stem/stromal cells: a comprehensive study with different immune cells.

    Science.gov (United States)

    Caires, Hugo R; Esteves, Tiago; Quelhas, Pedro; Barbosa, Mário A; Navarro, Melba; Almeida, Catarina R

    2016-09-01

    Despite the importance of immune cell-biomaterial interactions for the regenerative outcome, few studies have investigated how distinct three-dimensional biomaterials modulate the immune cell-mediated mesenchymal stem/stromal cells (MSC) recruitment and function. Thus, this work compares the response of varied primary human immune cell populations triggered by different model scaffolds and describes its functional consequence on recruitment and motility of bone marrow MSC. It was found that polylactic acid (PLA) and chitosan scaffolds lead to an increase in the metabolic activity of macrophages but not of peripheral blood mononuclear cells (PBMC), natural killer (NK) cells or monocytes. PBMC and NK cells increase their cell number in PLA scaffolds and express a secretion profile that does not promote MSC recruitment. Importantly, chitosan increases IL-8, MIP-1, MCP-1 and RANTES secretion by macrophages while PLA stimulates IL-6, IL-8 and MCP-1 production, all chemokines that can lead to MSC recruitment. This secretion profile of macrophages in contact with biomaterials correlates with the highest MSC invasion. Furthermore, macrophages enhance stem cell motility within chitosan scaffolds by 44% but not in PLA scaffolds. Thus, macrophages are the cells that in contact with engineered biomaterials become activated to secrete bioactive molecules that stimulate MSC recruitment.

  10. Tissue distribution and engraftment of human mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene

    DEFF Research Database (Denmark)

    Bentzon, J F; Stenderup, K; Hansen, F D

    2005-01-01

    Engraftment of mesenchymal stem cells (MSC) in peripheral tissues for replenishing of local stem cell function has been proposed as a therapeutic approach to degenerative diseases. We have previously reported the development of an immortalized human telomerase reverse transcriptase transduced MSC...... line (hMSC-TERT). In the present study, we co-transduced hMSC-TERT with enhanced green fluorescent protein gene, and studied tissue distribution, engraftment, and cell survival after intracardiac and intravenous injections in immunodeficient mice. The pattern of organ distribution suggested...... that infused cells were efficiently arrested in microvasculature during first-pass, but only for a fraction of the infused cells was arrest followed by vascular emigration and tissue engraftment. Few engrafted cells in lungs, heart, and kidney glomeruli remained after 4 weeks. These observations are consistent...

  11. THE LOCALIZATION OF ADRENOMEDULLIN IN RAT KIDNEY TISSUE AND ITS INHIBITORY EFFECT ON THE GROWTH OF CULTURED RAT MESANGIAL CELLS

    Institute of Scientific and Technical Information of China (English)

    刘学光; 张志刚; 张秀荣; 朱虹光; 陈琦; 郭慕依

    2002-01-01

    Objective. To observe the localization of adrenomedullin (AM) in rat kidney tissue and its inhibitory effect on the growth of cultured rat mesangial cells (MsC). Methods. A monoclonal antibody against AM developed by our laboratory was used to detect the localization of AM protein in rat kidney tissue by avidin-biotin complex immunohistochemistry. The expressions of AM and its receptor CRLR mRNA on cultured glomerular epithelial cells (GEC) and MsC were investigated by Northern blot assay, and the possible effect of AM secreted by GEC on MsC proliferation was observed using [3H]thymidine incorporation as an index. Results. A specific monoclonal antibody against AM was successfully developed. AM was immunohistochemically localized mainly in glomeruli (GEC and endothelial cells), some cortical proximal tubules, medullary collecting duct cells, interstitial cells, vascular smooth muscle cells and endothelial cells. Northern blot assay showed that AM mRNA was expressed only on cultured GEC, but not on MsC, however, AM receptor CRLR mRNA was only expressed on MsC. GEC conditioned medium containing AM can inhibit MsC growth and AM receptor blocker CGRP8-37 may partially decreased this inhibitory effect. Conclusion. AM produced by GEC inhibits the proliferation of MsC, which suggests that AM as an important regulator is involved in glomerular normal physiological functions and pathologic processes.

  12. Integrin expression in stem cells from bone marrow and adipose tissue during chondrogenic differentiation.

    Science.gov (United States)

    Goessler, Ulrich Reinhart; Bugert, Peter; Bieback, Karen; Stern-Straeter, Jens; Bran, Gregor; Hörmann, Karl; Riedel, Frank

    2008-03-01

    The use of adult mesenchymal stem cells (MSC) in cartilage tissue engineering offers new perspectives in the generation of transplants for reconstructive surgery. The extracelular matrix (ECM) plays a key role in modulating the function and phenotype of the embedded cells and contains the integrins as adhesion receptors mediating cell-cell and cell-matrix interactions. In our study, characteristic changes in integrin expression during the course of chondrogenic differentiation of MSC from bone marrow and adipose tissue were compared. MSC were isolated from bone marrow biopsies and adipose tissue. During cell culture, chondrogenic differentiation was performed. The expression of integrins and their signaling components were analysed with microarray and immunohistochemistry in freshly isolated MSC and after chondrogenic differentiation. The fibronectin receptor (integrin alpha5beta1) was expressed by undifferentiated MSC, and expression rose during chondrogenic differentiation in both types of MSC. The components of the vitronectin/osteopontin receptors (alphavbeta5) were not expressed by freshly isolated MSC, and expression rose with ongoing differentiation. Receptors for the collagens (alpha1beta1, alpha2beta1, alpha3beta1) were weakly expressed by undifferentiated MSC and were activated during differentiation. Intracellular signaling components integrin-linked kinase (ILK) and CD47 showed increased expression with ongoing differentiation. For all integrins, no significant differences were be found in the 2 types of MSC. Integrin-mediated signaling appeared to play an important role in the generation and maintenance of the chondrocytic phenotype during chondrogenic differentiation. Particularly, the receptors for fibronectin, vitronectin, osteopontin and the collagens may be involved in the generation of the ECM. Intracellularly, their signals might be transduced by ILK and CD47. To fully harness the potential of these cells, future studies should be directed to

  13. Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization

    DEFF Research Database (Denmark)

    Elsafadi, E; Manikandan, M; Dawud, R. A.

    2016-01-01

    in cellular and nuclear morphology and cytoplasmic organelle composition as demonstrated by high content imaging and transmission electron microscopy that revealed pronounced alterations in the distribution of the actin filament and changes in cytoskeletal organization. Molecular signature of TAGLN......MSC by regulating cytoskeleton organization. Targeting TAGLN is a plausible approach to enrich for committed hMSC cells needed for regenerative medicine application....

  14. Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with differentiation fate determination of human bone marrow stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Qiu, Weimin; Chen, Li; Kassem, Moustapha

    2011-01-01

    The canonical Wnt signaling pathway can determine human bone marrow stromal (mesenchymal) stem cell (hMSC) differentiation fate into osteoblast or adipocyte lineages. However, its downstream targets in MSC are not well characterized. Thus, using DNA microarrays, we compared global gene expression...

  15. Human Cardiac Mesenchymal Stromal Cells with CD105+CD34- Phenotype Enhance the Function of Post-Infarction Heart in Mice.

    Directory of Open Access Journals (Sweden)

    Justyna Czapla

    Full Text Available The aim of the present study was to isolate mesenchymal stromal cells (MSC with CD105+CD34- phenotype from human hearts, and to investigate their therapeutic potential in a mouse model of hindlimb ischemia and myocardial infarction (MI. The study aimed also to investigate the feasibility of xenogeneic MSCs implantation.MSC isolated from human hearts were multipotent cells. Separation of MSC with CD105+CD34- phenotype limited the heterogeneity of the originally isolated cell population. MSC secreted a number of anti-inflammatory and proangiogenic cytokines (mainly IL-6, IL-8, and GRO. Human MSC were transplanted into C57Bl/6NCrl mice. Using the mouse model of hindlimb ischemia it was shown that human MSC treated mice demonstrated a higher capillary density 14 days after injury. It was also presented that MSC administrated into the ischemic muscle facilitated fast wound healing (functional recovery by ischemic limb. MSC transplanted into an infarcted myocardium reduced the post-infarction scar, fibrosis, and increased the number of blood vessels both in the border area, and within the post-infarction scar. The improvement of left ventricular ejection fraction was also observed.In two murine models (hindlimb ischemia and MI we did not observe the xenotransplant rejection. Indeed, we have shown that human cardiac mesenchymal stromal cells with CD105+CD34- phenotype exhibit therapeutic potential. It seems that M2 macrophages are essential for healing and repair of the post-infarcted heart.

  16. Human Cardiac Mesenchymal Stromal Cells with CD105+CD34- Phenotype Enhance the Function of Post-Infarction Heart in Mice

    Science.gov (United States)

    Wiśniewska, Ewa; Jarosz-Biej, Magdalena; Smolarczyk, Ryszard; Cichoń, Tomasz; Głowala-Kosińska, Magdalena; Śliwka, Joanna; Garbacz, Marcin; Szczypior, Mateusz; Jaźwiec, Tomasz; Langrzyk, Agnieszka; Zembala, Michał; Szala, Stanisław

    2016-01-01

    Aims The aim of the present study was to isolate mesenchymal stromal cells (MSC) with CD105+CD34- phenotype from human hearts, and to investigate their therapeutic potential in a mouse model of hindlimb ischemia and myocardial infarction (MI). The study aimed also to investigate the feasibility of xenogeneic MSCs implantation. Methods and Results MSC isolated from human hearts were multipotent cells. Separation of MSC with CD105+CD34- phenotype limited the heterogeneity of the originally isolated cell population. MSC secreted a number of anti-inflammatory and proangiogenic cytokines (mainly IL-6, IL-8, and GRO). Human MSC were transplanted into C57Bl/6NCrl mice. Using the mouse model of hindlimb ischemia it was shown that human MSC treated mice demonstrated a higher capillary density 14 days after injury. It was also presented that MSC administrated into the ischemic muscle facilitated fast wound healing (functional recovery by ischemic limb). MSC transplanted into an infarcted myocardium reduced the post-infarction scar, fibrosis, and increased the number of blood vessels both in the border area, and within the post-infarction scar. The improvement of left ventricular ejection fraction was also observed. Conclusion In two murine models (hindlimb ischemia and MI) we did not observe the xenotransplant rejection. Indeed, we have shown that human cardiac mesenchymal stromal cells with CD105+CD34- phenotype exhibit therapeutic potential. It seems that M2 macrophages are essential for healing and repair of the post-infarcted heart. PMID:27415778

  17. Conditioned medium from mesenchymal stem cells induces cell death in organotypic cultures of rat hippocampus and aggravates lesion in a model of oxygen and glucose deprivation.

    Science.gov (United States)

    Horn, Ana Paula; Frozza, Rudimar Luiz; Grudzinski, Patrícia Benke; Gerhardt, Daniéli; Hoppe, Juliana Bender; Bruno, Alessandra Nejar; Chagastelles, Pedro; Nardi, Nance Beyer; Lenz, Guido; Salbego, Christianne

    2009-01-01

    Cell therapy using bone marrow-derived mesenchymal stem cells (MSC) seems to be a new alternative for the treatment of neurological diseases, including stroke. In order to investigate the response of hippocampal tissue to factors secreted by MSC and if these factors are neuroprotective in a model of oxygen and glucose deprivation (OGD), we used organotypic hippocampal cultures exposed to conditioned medium from bone marrow-derived MSC. Our results suggest that the conditioned medium obtained from these cells aggravates lesion caused by OGD. In addition, the presence of the conditioned medium alone was toxic mainly to cells in the CA1, CA2 and CA3 areas of the hippocampal organotypic culture even in basal conditions. GABA stimulation and NMDA and AMPA receptors antagonists were able to reduce propidium iodide staining, suggesting that the cell death induced by the toxic factors secreted by MSC could involve these receptors.

  18. Polycaprolactone nanomesh cultured with hMSC evaluated by synchrotron tomography

    DEFF Research Database (Denmark)

    Nygaard, Jens Vinge; Andersen, Morten Østergaard; Cloetens, Peter

    2009-01-01

    substrates while proliferating preferentially on the stiffer ones. This implicates that substrate rigidity is a critical design parameter in the development of scaffolds aimed at eliciting maximal cell and tissue function. From mechanics it is known that the stiffness of a porous structures scales...... with the relative density of the porous material, [2]. Hence, variations of substrate rigidity can be controlled through changes in relative density of the substrate itself. In three dimensional porous scaffolds, the substrate is equivalent to struts or beams randomly orientated in space making an interconnected...... network. These beams are called Plateau borders and are typically solid structures. Thus their stiffness depends solely on the stiffness of the selected biopolymer and the method of production. In this study we demonstrate that it is possible to control the porosity not only of the macroscopic porous...

  19. Polycaprolactone nanomesh cultured with hMSC evaluated by synchrotron tomography

    DEFF Research Database (Denmark)

    Nygaard, Jens Vinge; Andersen, Morten Østergaard; Cloetens, Peter

    substrates while proliferating preferentially on the stiffer ones. This implicates that substrate rigidity is a critical design parameter in the development of scaffolds aimed at eliciting maximal cell and tissue function. From mechanics it is known that the stiffness of a porous structures scales...... with the relative density of the porous material, [2]. Hence, variations of substrate rigidity can be controlled through changes in relative density of the substrate itself. In three dimensional porous scaffolds, the substrate is equivalent to struts or beams randomly orientated in space making an interconnected...... network. These beams are called Plateau borders and are typically solid structures. Thus their stiffness depends solely on the stiffness of the selected biopolymer and the method of production. In this study we demonstrate that it is possible to control the porosity not only of the macroscopic porous...

  20. Ostracism Online: A social media ostracism paradigm.

    Science.gov (United States)

    Wolf, Wouter; Levordashka, Ana; Ruff, Johanna R; Kraaijeveld, Steven; Lueckmann, Jan-Matthis; Williams, Kipling D

    2015-06-01

    We describe Ostracism Online, a novel, social media-based ostracism paradigm designed to (1) keep social interaction experimentally controlled, (2) provide researchers with the flexibility to manipulate the properties of the social situation to fit their research purposes, (3) be suitable for online data collection, (4) be convenient for studying subsequent within-group behavior, and (5) be ecologically valid. After collecting data online, we compared the Ostracism Online paradigm with the Cyberball paradigm (Williams & Jarvis Behavior Research Methods, 38, 174-180, 2006) on need-threat and mood questionnaire scores (van Beest & Williams Journal of Personality and Social Psychology 91, 918-928, 2006). We also examined whether ostracized targets of either paradigm would be more likely to conform to their group members than if they had been included. Using a Bayesian analysis of variance to examine the individual effects of the different paradigms and to compare these effects across paradigms, we found analogous effects on need-threat and mood. Perhaps because we examined conformity to the ostracizers (rather than neutral sources), neither paradigm showed effects of ostracism on conformity. We conclude that Ostracism Online is a cost-effective, easy to use, and ecologically valid research tool for studying the psychological and behavioral effects of ostracism.

  1. Liver-specific gene expression in mesenchymal stem cells is induced by liver cells

    Institute of Scientific and Technical Information of China (English)

    Claudia Lange; Philipp Bassler; Michael V. Lioznov; Helge Bruns; Dietrich Kluth; Axel R. Zander; Henning C. Fiegel

    2005-01-01

    AIM: The origin of putative liver cells from distinct bone marrow stem cells, e.g. hematopoietic stem cells or multipotent adult progenitor cells was found in recent in vitro studies. Cell culture experiments revealed a key role of growth factors for the induction of liver-specific genes in stem cell cultures. We investigated the potential of rat mesenchymal stem cells (MSC) from bone marrow to differentiate into hepatocytic cells in vitro. Furthermore,we assessed the influence of cocultured liver cells on induction of liver-specific gene expression.METHODS: Mesenchymal stem cells were marked with green fluorescent protein (GFP) by retroviral gene transduction. Clonal marked MSC were either cultured under liver stimulating conditions using fibronectin-coated culture dishes and medium supplemented with SCF, HGF,EGF, and FGF-4 alone, or in presence of freshly isolated rat liver cells. Cells in cocultures were harvested and GFP+ or GFP- cells were separated using fluorescence activated cell sorting. RT-PCR analysis for the stem cell marker Thy1 and the hepatocytic markers CK-18, albumin, CK-19,and AFP was performed in the different cell populations.RESULTS: Under the specified culture conditions, rat MSC cocultured with liver cells expressed albumin-, CK-18,CK-19, and AFP-RNA over 3 weeks, whereas MSC cultured alone did not show liver specific gene expression.CONCLUSION: The results indicate that (1) rat MSC from bone marrow can differentiate towards hepatocytic lineage in vitro, and (2) that the microenvironment plays a decisive role for the induction of hepatic differentiation of rMSC.

  2. The cognitive paradigm ontology: design and application.

    Science.gov (United States)

    Turner, Jessica A; Laird, Angela R

    2012-01-01

    We present the basic structure of the Cognitive Paradigm Ontology (CogPO) for human behavioral experiments. While the experimental psychology and cognitive neuroscience literature may refer to certain behavioral tasks by name (e.g., the Stroop paradigm or the Sternberg paradigm) or by function (a working memory task, a visual attention task), these paradigms can vary tremendously in the stimuli that are presented to the subject, the response expected from the subject, and the instructions given to the subject. Drawing from the taxonomy developed and used by the BrainMap project ( www.brainmap.org ) for almost two decades to describe key components of published functional imaging results, we have developed an ontology capable of representing certain characteristics of the cognitive paradigms used in the fMRI and PET literature. The Cognitive Paradigm Ontology is being developed to be compliant with the Basic Formal Ontology (BFO), and to harmonize where possible with larger ontologies such as RadLex, NeuroLex, or the Ontology of Biomedical Investigations (OBI). The key components of CogPO include the representation of experimental conditions focused on the stimuli presented, the instructions given, and the responses requested. The use of alternate and even competitive terminologies can often impede scientific discoveries. Categorization of paradigms according to stimulus, response, and instruction has been shown to allow advanced data retrieval techniques by searching for similarities and contrasts across multiple paradigm levels. The goal of CogPO is to develop, evaluate, and distribute a domain ontology of cognitive paradigms for application and use in the functional neuroimaging community.

  3. Medialogy (English Information Brochure on the education M.Sc.,Medialogy, 3rd to 10th semester (B.Sc. & M.Sc) - For graduates from higher study programmes such as Multimedia Design and IT Graduates)

    DEFF Research Database (Denmark)

    Nordahl, Rolf

    2005-01-01

    An information brochure, 24 pages, in English which describes the education M.Sc., Medialogy, offered by Aalborg University in Copenhagen and Esbjerg. The brochure describes the 3rd to 10th semester (B.Sc. and M.Sc. degree) of the education. The information is primarily directed toward potential...

  4. Gene Delivery of TGF-β3 and BMP2 in an MSC-Laden Alginate Hydrogel for Articular Cartilage and Endochondral Bone Tissue Engineering.

    Science.gov (United States)

    Gonzalez-Fernandez, Tomas; Tierney, Erica G; Cunniffe, Grainne M; O'Brien, Fergal J; Kelly, Daniel J

    2016-05-01

    Incorporating therapeutic genes into three-dimensional biomaterials is a promising strategy for enhancing tissue regeneration. Alginate hydrogels have been extensively investigated for cartilage and bone tissue engineering, including as carriers of transfected cells to sites of injury, making them an ideal gene delivery platform for cartilage and osteochondral tissue engineering. The objective of this study was to develop gene-activated alginate hydrogels capable of supporting nanohydroxyapatite (nHA)-mediated nonviral gene transfer to control the phenotype of mesenchymal stem cells (MSCs) for either cartilage or endochondral bone tissue engineering. To produce these gene-activated constructs, MSCs and nHA complexed with plasmid DNA (pDNA) encoding for transforming growth factor-beta 3 (pTGF-β3), bone morphogenetic protein 2 (pBMP2), or a combination of both (pTGF-β3-pBMP2) were encapsulated into alginate hydrogels. Initial analysis using reporter genes showed effective gene delivery and sustained overexpression of the transgenes were achieved. Confocal microscopy demonstrated that complexing the plasmid with nHA before hydrogel encapsulation led to transport of the plasmid into the nucleus of MSCs, which did not happen with naked pDNA. Gene delivery of TGF-β3 and BMP2 and subsequent cell-mediated expression of these therapeutic genes resulted in a significant increase in sulfated glycosaminoglycan and collagen production, particularly in the pTGF-β3-pBMP2 codelivery group in comparison to the delivery of either pTGF-β3 or pBMP2 in isolation. In addition, stronger staining for collagen type II deposition was observed in the pTGF-β3-pBMP2 codelivery group. In contrast, greater levels of calcium deposition were observed in the pTGF-β3- and pBMP2-only groups compared to codelivery, with a strong staining for collagen type X deposition, suggesting these constructs were supporting MSC hypertrophy and progression along an endochondral pathway. Together, these

  5. Fuzzy Hybrid Deliberative/Reactive Paradigm (FHDRP)

    Science.gov (United States)

    Sarmadi, Hengameth

    2004-01-01

    This work aims to introduce a new concept for incorporating fuzzy sets in hybrid deliberative/reactive paradigm. After a brief review on basic issues of hybrid paradigm the definition of agent-based fuzzy hybrid paradigm, which enables the agents to proceed and extract their behavior through quantitative numerical and qualitative knowledge and to impose their decision making procedure via fuzzy rule bank, is discussed. Next an example performs a more applied platform for the developed approach and finally an overview of the corresponding agents architecture enhances agents logical framework.

  6. [Human umbilical cord mesenchymal stem cells reduce the sensitivity of HL-60 cells to cytarabine].

    Science.gov (United States)

    Cui, Jun-Jie; Chi, Ying; Du, Wen-Jing; Yang, Shao-Guang; Li, Xue; Chen, Fang; Ma, Feng-Xia; Lu, Shi-Hong; Han, Zhong-Chao

    2013-06-01

    This study was purposed to investigate the impact of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) on the sensitivity of HL-60 cells to therapeutic drugs so as to provide more information for exploring the regulatory effect of hUC-MSC on leukemia cells. Transwell and direct co-culture systems of HL-60 and hUC-MSC were established. The apoptosis and cell cycle of HL-60 cells were detected by flow cytometry. RT-PCR and Western blot were used to detect the mRNA and protein levels of Caspase 3, respectively. The results showed that the apoptosis of HL-60 induced by cytarabine (Ara-C) decreased significantly after direct co-cultured with hUC-MSC cycle mRNA (P HL-60 cells were arrested at G0/G1 phase and did not enter into S phase (P HL-60 cells were reduced (P HL-60 from Arc-C induced apoptosis through regulating the cell cycle and down-regulating expression of Caspase 3 in HL-60 cells. In addition, this effect is caused by the soluble factors from hUC-MSC.

  7. Contemporary Treatment Paradigms in Keratoconus.

    Science.gov (United States)

    McGhee, Charles N J; Kim, Bia Z; Wilson, Peter J

    2015-10-01

    The past 20 years have witnessed an explosion in our knowledge of keratoconus, accompanied by a radical transformation of management options. A 2-hit hypothesis proposes an underlying genetic predisposition coupled with external environmental factors, including eye rubbing and atopy. The variable prevalence and natural history have been better defined including significant cone progression in middle age. Therefore, current management must include early diagnosis, regular monitoring, and treatment of environmental cofactors. Spectacles and contact lenses remain fundamental to the optical management of keratoconus. Intrastromal corneal ring segments have been increasingly used, providing improvement in the corneal shape, corrected visual acuity, and contact lens wear. However, like contact lenses, intrastromal corneal ring segments do not treat the underlying disease process. Therefore, current approaches must also consider treatments to minimize keratoconus progression. Fortunately, there is increasing evidence that corneal collagen crosslinking will halt or slow progression in most cases. Until relatively recently, penetrating keratoplasty was the preferred intervention for advanced keratoconus, with long-term success in the region of 90%; however, the greatest risk of failure remains endothelial allograft rejection. Deep anterior lamellar keratoplasty has emerged in the new millennium as a preferred approach to conserve the host endothelium and avoid rejection. Nonetheless, the overall superiority of deep anterior lamellar keratoplasty compared with penetrating keratoplasty, in terms of optical and survival benefits, is still debated. This perspective provides an overview of our current knowledge of keratoconus and current management options. A step-ladder approach to managing keratoconus is outlined to provide the practitioner with a contemporary management paradigm.

  8. dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors

    DEFF Research Database (Denmark)

    Abdallah, Basem M.; Boissy, Patrice; Tan, Qihua

    2007-01-01

    dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain...... the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control hMSC (negative for Dlk1 expression) by using Affymetrix......, apoptosis, and cell adhesion. Also, addition of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner. As biological consequences of up-regulating these immune response-related factors, we showed that the inhibitory effects of dlk1 on osteoblast and adipocyte differentiation of h...

  9. Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Peter Succar

    2016-01-01

    Full Text Available Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC therapy are gaining acceptance for knee-osteoarthritis (OA treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL. At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA.

  10. Polyhydroxyalkanoates: waste glycerol upgrade into electrospun fibrous scaffolds for stem cells culture

    OpenAIRE

    Canadas, Raphael Faustino; Cavalheiro, João M. B. T.; Guerreiro, João D. T.; Almeida, M. Catarina M. D. de; Pollet, Eric; Silva, Cláudia Lobato da; Fonseca, M.M.R. da; Ferreira, Frederico Castelo

    2014-01-01

    This integrated study shows that waste glycerol can be bio-valorized by the fabrication of electrospun scaffolds for stem cells. Human mesenchymal stem cells (hMSC) provide an interesting model of regenerating cells because of their ability to differentiate into osteo-, chrondro-, adipo- and myogenic lineages. Moreover, hMSC have modulatory properties with potential on treatment of immunologic diseases. Electrospun fiber meshes offer tunable mechanical and physical properties that can mimic t...

  11. Dielectrophoretic study of human embryonic stem cells and their differentiated progeny

    OpenAIRE

    Velugotla, Srinivas

    2013-01-01

    This thesis describes for the first time, how the membrane capacitance of pluripotent human embryonic stem cells (H1, H9, RCM1) increases with their differentiation (H1-MSC, H9-MSC, RCM1-trophoblast) based on the literature review. The method used to determine membrane capacitance was dielectrophoresis (DEP), which is an electrokinetic technique capable of characterising and sorting cells without the need for antibody-based cell surface markers, magnetic beads, or other chemica...

  12. Mesenchymal stem cell mechanobiology and emerging experimental platforms.

    Science.gov (United States)

    MacQueen, Luke; Sun, Yu; Simmons, Craig A

    2013-07-06

    Experimental control over progenitor cell lineage specification can be achieved by modulating properties of the cell's microenvironment. These include physical properties of the cell adhesion substrate, such as rigidity, topography and deformation owing to dynamic mechanical forces. Multipotent mesenchymal stem cells (MSCs) generate contractile forces to sense and remodel their extracellular microenvironments and thereby obtain information that directs broad aspects of MSC function, including lineage specification. Various physical factors are important regulators of MSC function, but improved understanding of MSC mechanobiology requires novel experimental platforms. Engineers are bridging this gap by developing tools to control mechanical factors with improved precision and throughput, thereby enabling biological investigation of mechanics-driven MSC function. In this review, we introduce MSC mechanobiology and review emerging cell culture platforms that enable new insights into mechanobiological control of MSCs. Our main goals are to provide engineers and microtechnology developers with an up-to-date description of MSC mechanobiology that is relevant to the design of experimental platforms and to introduce biologists to these emerging platforms.

  13. Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Yuben Moodley

    2016-07-01

    Full Text Available Acute lung injury/acute respiratory distress syndrome (ALI/ARDS is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC have shown promise in treating inflammatory lung conditions. We hypothesised that human MSC (hMSC can improve ALI/ARDS through their anti-inflammatory actions. We subjected pigs (n = 6 to intravenous oleic acid (OA injury, ventilation and hMSC infusion, while the controls (n = 5 had intravenous OA, ventilation and an infusion vehicle control. hMSC were infused 1 h after the administration of OA. The animals were monitored for additional 4 h. Nuclear translocation of nuclear factor-light chain enhancer of activated B cells (NF-κB, a transcription factor that mediates several inflammatory pathways was reduced in hMSC treated pigs compared to controls (p = 0.04. There was no significant difference in lung injury, assessed by histological scoring in hMSC treated pigs versus controls (p = 0.063. There was no difference in neutrophil counts between hMSC-treated pigs and controls. Within 4 h, there was no difference in the levels of IL-10 and IL-8 pre- and post-treatment with hMSC. In addition, there was no difference in hemodynamics, lung mechanics or arterial blood gases between hMSC treated animals and controls. Subsequent studies are required to determine if the observed decrease in inflammatory transcription factors will translate into improvement in inflammation and in physiological parameters over the long term.

  14. Mesenchymal Stromal Cells Do Not Increase the Risk of Viral Reactivation Nor the Severity of Viral Events in Recipients of Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Giovanna Lucchini

    2012-01-01

    Full Text Available Mesenchymal stromal cells (MSC are tested in clinical trials to treat graft versus host disease (GvHD after stem cell transplantation (SCT. In vitro studies demonstrated MSC's broad immunosuppressive activity. As infections represent a major risk after SCT, it is important to understand the role of MSC in this context. We analyzed 24 patients (pts receiving MSC for GvHD in our Unit between 2009 and 2011. We recorded viral reactivations as measured in whole blood with polymerase chain reaction for 100 days following MSC administration. In patients with a documented viral reactivation in the first 3 days following MSCs infusion the frequency of virus-specific IFNgamma-producing cells was determined through enzyme-linked immunospot assay. In our cohort of patients viral reactivation after MSC infusion occurred in 45% of the cases, which did not significantly differ from the incidence in a historical cohort of patients affected by steroid resistant GvHD and treated with conventional immunosuppression. No patient presented severe form of infection. Two cases could be checked for immunological response to viral stimulus and demonstrated virus specific T-cytotoxic lymphocyte activity. In our experience MSC infusion did not prove to trigger more frequent or severer viral reactivations in the post transplantation setting.

  15. Paradigms and pragmatism: approaches to medical statistics.

    Science.gov (United States)

    Healy, M J

    2000-01-01

    Until recently, the dominant philosophy of science was that due to Karl Popper, with its doctrine that the proper task of science was the formulation of hypotheses followed by attempts at refuting them. In spite of the close analogy with significance testing, these ideas do not fit well with the practice of medical statistics. The same can be said of the later philosophy of Thomas Kuhn, who maintains that science proceeds by way of revolutionary upheavals separated by periods of relatively pedestrian research which are governed by what Kuhn refers to as paradigms. Through there have been paradigm shifts in the history of statistics, a degree of continuity can also be discerned. A current paradigm shift is embodied in the spread of Bayesian ideas. It may be that a future paradigm will emphasise the pragmatic approach to statistics that is associated with the name of Daniel Schwartz.

  16. Levelling in the German Verb Paradigm

    Science.gov (United States)

    Newman, John

    1974-01-01

    Levelling processes in the history of the German verb paradigm from Old High German to the present are discussed. It is asserted that the theory of transformational generative grammar provides a proper framework for the study of linguistic change. (RM)

  17. The safety implications of emerging software paradigms

    Energy Technology Data Exchange (ETDEWEB)

    Suski, G.J.; Persons, W.L.; Johnson, G.L.

    1994-10-01

    This paper addresses some of the emerging software paradigms that may be used in developing safety-critical software applications. Paradigms considered in this paper include knowledge-based systems, neural networks, genetic algorithms, and fuzzy systems. It presents one view of the software verification and validation activities that should be associated with each paradigm. The paper begins with a discussion of the historical evolution of software verification and validation. Next, a comparison is made between the verification and validation processes used for conventional and emerging software systems. Several verification and validation issues for the emerging paradigms are discussed and some specific research topics are identified. This work is relevant for monitoring and control at nuclear power plants.

  18. Yakov Zeldovich and the Cosmic Web Paradigm

    CERN Document Server

    Einasto, Jaan

    2014-01-01

    I discuss the formation of the modern cosmological paradigm. In more detail I describe the early study of dark matter and cosmic web and the role of Yakov Zeldovich in the formation of the present concepts on these subjects.

  19. Yakov Zeldovich and the Cosmic Web Paradigm

    Science.gov (United States)

    Einasto, Jaan

    2016-10-01

    I discuss the formation of the modern cosmological paradigm. In more detail I describe the early study of dark matter and cosmic web and the role of Yakov Zeldovich in the formation of the present concepts on these subjects.

  20. Engineering paradigms and anthropogenic global change

    Science.gov (United States)

    Bohle, Martin

    2016-04-01

    This essay discusses 'paradigms' as means to conceive anthropogenic global change. Humankind alters earth-systems because of the number of people, the patterns of consumption of resources, and the alterations of environments. This process of anthropogenic global change is a composite consisting of societal (in the 'noosphere') and natural (in the 'bio-geosphere') features. Engineering intercedes these features; e.g. observing stratospheric ozone depletion has led to understanding it as a collateral artefact of a particular set of engineering choices. Beyond any specific use-case, engineering works have a common function; e.g. civil-engineering intersects economic activity and geosphere. People conceive their actions in the noosphere including giving purpose to their engineering. The 'noosphere' is the ensemble of social, cultural or political concepts ('shared subjective mental insights') of people. Among people's concepts are the paradigms how to shape environments, production systems and consumption patterns given their societal preferences. In that context, engineering is a means to implement a given development path. Four paradigms currently are distinguishable how to make anthropogenic global change happening. Among the 'engineering paradigms' for anthropogenic global change, 'adaptation' is a paradigm for a business-as-usual scenario and steady development paths of societies. Applying this paradigm implies to forecast the change to come, to appropriately design engineering works, and to maintain as far as possible the current production and consumption patterns. An alternative would be to adjust incrementally development paths of societies, namely to 'dovetail' anthropogenic and natural fluxes of matter and energy. To apply that paradigm research has to identify 'natural boundaries', how to modify production and consumption patterns, and how to tackle process in the noosphere to render alterations of common development paths acceptable. A further alternative

  1. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

    Directory of Open Access Journals (Sweden)

    Sean D. Owens

    2016-01-01

    Full Text Available Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM or adipose tissue derived MSCs (ad-MSCs were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89% were positive for anti-bovine serum albumin (BSA antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.

  2. Parabens determination in cosmetic and personal care products exploiting a multi-syringe chromatographic (MSC) system and chemiluminescent detection.

    Science.gov (United States)

    Rodas, Melisa; Portugal, Lindomar A; Avivar, Jessica; Estela, José Manuel; Cerdà, Víctor

    2015-10-01

    Parabens are widely used in dairy products, such as in cosmetics and personal care products. Thus, in this work a multi-syringe chromatographic (MSC) system is proposed for the first time for the determination of four parabens: methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) in cosmetics and personal care products, as a simpler, practical, and low cost alternative to HPLC methods. Separation was achieved using a 5mm-long precolumn of reversed phase C18 and multi-isocratic separation, i.e. using two consecutive mobile phases, 12:88 acetonitrile:water and 28:72 acetonitrile:water. The use of a multi-syringe buret allowed the easy implementation of chemiluminescent (CL) detection after separation. The chemiluminescent detection is based on the reduction of Ce(IV) by p-hydroxybenzoic acid, product of the acid hydrolysis of parabens, to excite rhodamine 6G (Rho 6G) and measure the resulting light emission. Multivariate designs combined with the concepts of multiple response treatments and desirability functions have been employed to simultaneously optimize and evaluate the responses. The optimized method has proved to be sensitive and precise, obtaining limits of detection between 20 and 40 µg L(-1) and RSD <4.9% in all cases. The method was satisfactorily applied to cosmetics and personal care products, obtaining no significant differences at a confidence level of 95% comparing with the HPLC reference method.

  3. MSC/NASTRAN DMAP Alter Used for Closed-Form Static Analysis With Inertia Relief and Displacement-Dependent Loads

    Science.gov (United States)

    1996-01-01

    Solving for the displacements of free-free coupled systems acted upon by static loads is a common task in the aerospace industry. Often, these problems are solved by static analysis with inertia relief. This technique allows for a free-free static analysis by balancing the applied loads with the inertia loads generated by the applied loads. For some engineering applications, the displacements of the free-free coupled system induce additional static loads. Hence, the applied loads are equal to the original loads plus the displacement-dependent loads. A launch vehicle being acted upon by an aerodynamic loading can have such applied loads. The final displacements of such systems are commonly determined with iterative solution techniques. Unfortunately, these techniques can be time consuming and labor intensive. Because the coupled system equations for free-free systems with displacement-dependent loads can be written in closed form, it is advantageous to solve for the displacements in this manner. Implementing closed-form equations in static analysis with inertia relief is analogous to implementing transfer functions in dynamic analysis. An MSC/NASTRAN (MacNeal-Schwendler Corporation/NASA Structural Analysis) DMAP (Direct Matrix Abstraction Program) Alter was used to include displacement-dependent loads in static analysis with inertia relief. It efficiently solved a common aerospace problem that typically has been solved with an iterative technique.

  4. Closed-form Static Analysis with Inertia Relief and Displacement-Dependent Loads Using a MSC/NASTRAN DMAP Alter

    Science.gov (United States)

    Barnett, Alan R.; Widrick, Timothy W.; Ludwiczak, Damian R.

    1995-01-01

    Solving for the displacements of free-free coupled systems acted upon by static loads is commonly performed throughout the aerospace industry. Many times, these problems are solved using static analysis with inertia relief. This solution technique allows for a free-free static analysis by balancing the applied loads with inertia loads generated by the applied loads. For some engineering applications, the displacements of the free-free coupled system induce additional static loads. Hence, the applied loads are equal to the original loads plus displacement-dependent loads. Solving for the final displacements of such systems is commonly performed using iterative solution techniques. Unfortunately, these techniques can be time-consuming and labor-intensive. Since the coupled system equations for free-free systems with displacement-dependent loads can be written in closed-form, it is advantageous to solve for the displacements in this manner. Implementing closed-form equations in static analysis with inertia relief is analogous to implementing transfer functions in dynamic analysis. Using a MSC/NASTRAN DMAP Alter, displacement-dependent loads have been included in static analysis with inertia relief. Such an Alter has been used successfully to solve efficiently a common aerospace problem typically solved using an iterative technique.

  5. Inter-professional work based learning within an MSc in Advanced Practice: lessons from one UK higher education programme.

    Science.gov (United States)

    Gaskell, Lynne; Beaton, Susan

    2010-09-01

    This paper will describe the implementation of inter-professional work based education (IPE) in one postgraduate Advanced Practitioner programme in the UK. The concept of Advanced Practice has developed as a response of a number of drivers including change in junior doctor training; government policy and increasing demands on the central government funded UK health service (the NHS). The programme was commissioned by the then greater Manchester Strategic Health Authority (now NHS North West) to meet service needs. The educational philosophy underpinning the MSc Advanced Practice (health and social care) provided by the University of Salford is IPE linked to work based learning. The process of work based learning (WBL) and inter-professional learning underpinning the programme will be discussed in relation to feedback from university staff, Advanced Practitioner (AP) students and employer feedback taken from programme and module evaluations. We argue that IPE at this level facilitates a greater understanding of the connectivity between professionals working in the health care system in the UK; a better understanding of the skills and knowledge base of colleagues; more inter-professional working and appropriate referrals in the work place. This has raised the profile of Advanced Practice (AP) in the region and ultimately resulted in better patient care with more effective and efficient use of resources (Acton Shapiro, 2006, 2008).

  6. New Indivisible Planetary Science Paradigm: Consequence of Questioning Popular Paradigms

    Science.gov (United States)

    Marvin Herndon, J.

    2014-05-01

    Progress in science involves replacing less precise understanding with more precise understanding. In science and in science education one should always question popular ideas; ask "What's wrong with this picture?" Finding limitations, conflicts or circumstances that require special ad hoc consideration sometimes is the key to making important discoveries. For example, from thermodynamic considerations, I found that the 'standard model of solar system formation' leads to insufficiently massive planetary cores. That understanding led me to discover a new indivisible planetary science paradigm. Massive-core planets formed by condensing and raining-out from within giant gaseous protoplanets at high pressures and high temperatures, accumulating heterogeneously on the basis of volatility with liquid core-formation preceding mantle-formation; the interior states of oxidation resemble that of the Abee enstatite chondrite. Core-composition was established during condensation based upon the relative solubilities of elements, including uranium, in liquid iron in equilibrium with an atmosphere of solar composition at high pressures and high temperatures. Uranium settled to the central region and formed planetary nuclear fission reactors, producing heat and planetary magnetic fields. Earth's complete condensation included a ~300 Earth-mass gigantic gas/ice shell that compressed the rocky kernel to about 66% of Earth's present diameter. T-Tauri eruptions, associated with the thermonuclear ignition of the Sun, stripped the gases away from the Earth and the inner planets. The T-Tauri outbursts stripped a portion of Mercury's incompletely condensed protoplanet and transported it to the region between Mars and Jupiter where it fused with in-falling oxidized condensate from the outer regions of the Solar System, forming the parent matter of ordinary chondrite meteorites, the main-Belt asteroids, and veneer for the inner planets, especially Mars. With its massive gas/ice shell

  7. How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

    Directory of Open Access Journals (Sweden)

    Liangpeng Li

    2016-01-01

    Full Text Available Mesenchymal stem cell (MSC is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question.

  8. Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging.

    Science.gov (United States)

    Parashurama, Natesh; Ahn, Byeong-Cheol; Ziv, Keren; Ito, Ken; Paulmurugan, Ramasamy; Willmann, Jürgen K; Chung, Jaehoon; Ikeno, Fumiaki; Swanson, Julia C; Merk, Denis R; Lyons, Jennifer K; Yerushalmi, David; Teramoto, Tomohiko; Kosuge, Hisanori; Dao, Catherine N; Ray, Pritha; Patel, Manishkumar; Chang, Ya-Fang; Mahmoudi, Morteza; Cohen, Jeff Eric; Goldstone, Andrew Brooks; Habte, Frezghi; Bhaumik, Srabani; Yaghoubi, Shahriar; Robbins, Robert C; Dash, Rajesh; Yang, Phillip C; Brinton, Todd J; Yock, Paul G; McConnell, Michael V; Gambhir, Sanjiv S

    2016-09-01

    Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (©) RSNA, 2016 Online supplemental material is available for this article.

  9. The Underlying Social Dynamics of Paradigm Shifts.

    Directory of Open Access Journals (Sweden)

    Carlos Rodriguez-Sickert

    Full Text Available We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm; and ii radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  10. The Underlying Social Dynamics of Paradigm Shifts.

    Science.gov (United States)

    Rodriguez-Sickert, Carlos; Cosmelli, Diego; Claro, Francisco; Fuentes, Miguel Angel

    2015-01-01

    We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  11. The Underlying Social Dynamics of Paradigm Shifts

    Science.gov (United States)

    Claro, Francisco; Fuentes, Miguel Angel

    2015-01-01

    We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm. PMID:26418255

  12. Collecting duct-derived cells display mesenchymal stem cell properties and retain selective in vitro and in vivo epithelial capacity.

    Science.gov (United States)

    Li, Joan; Ariunbold, Usukhbayar; Suhaimi, Norseha; Sunn, Nana; Guo, Jinjin; McMahon, Jill A; McMahon, Andrew P; Little, Melissa

    2015-01-01

    We previously described a mesenchymal stem cell (MSC)-like population within the adult mouse kidney that displays long-term colony-forming efficiency, clonogenicity, immunosuppression, and panmesodermal potential. Although phenotypically similar to bone marrow (BM)-MSCs, kidney MSC-like cells display a distinct expression profile. FACS sorting from Hoxb7/enhanced green fluorescent protein (GFP) mice identified the collecting duct as a source of kidney MSC-like cells, with these cells undergoing an epithelial-to-mesenchymal transition to form clonogenic, long-term, self-renewing MSC-like cells. Notably, after extensive passage, kidney MSC-like cells selectively integrated into the aquaporin 2-positive medullary collecting duct when microinjected into the kidneys of neonatal mice. No epithelial integration was observed after injection of BM-MSCs. Indeed, kidney MSC-like cells retained a capacity to form epithelial structures in vitro and in vivo, and conditioned media from these cells supported epithelial repair in vitro. To investigate the origin of kidney MSC-like cells, we further examined Hoxb7(+) fractions within the kidney across postnatal development, identifying a neonatal interstitial GFP(lo) (Hoxb7(lo)) population displaying an expression profile intermediate between epithelium and interstitium. Temporal analyses with Wnt4(GCE/+):R26(tdTomato/+) mice revealed evidence for the intercalation of a Wnt4-expressing interstitial population into the neonatal collecting duct, suggesting that such intercalation may represent a normal developmental mechanism giving rise to a distinct collecting duct subpopulation. These results extend previous observations of papillary stem cell activity and collecting duct plasticity and imply a role for such cells in collecting duct formation and, possibly, repair.

  13. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology

    Science.gov (United States)

    2016-01-01

    Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells present in most fetal and adult tissues. Ex vivo culture-expanded MSCs are being investigated for tissue repair and immune modulation, but their full clinical potential is far from realization. Here we review the role of oxidative stress in MSC biology, as their longevity and functions are affected by oxidative stress. In general, increased reactive oxygen species (ROS) inhibit MSC proliferation, increase senescence, enhance adipogenic but reduce osteogenic differentiation, and inhibit MSC immunomodulation. Furthermore, aging, senescence, and oxidative stress reduce their ex vivo expansion, which is critical for their clinical applications. Modulation of sirtuin expression and activity may represent a method to reduce oxidative stress in MSCs. These findings have important implications in the clinical utility of MSCs for degenerative and immunological based conditions. Further study of oxidative stress in MSCs is imperative in order to enhance MSC ex vivo expansion and in vivo engraftment, function, and longevity. PMID:27413419

  14. Mesenchymal stem cells induce T-cell tolerance and protect the preterm brain after global hypoxia-ischemia.

    Directory of Open Access Journals (Sweden)

    Reint K Jellema

    Full Text Available Hypoxic-ischemic encephalopathy (HIE in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 10(6 MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI, in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE.

  15. Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids

    Science.gov (United States)

    Ankrum, James A.; Dastidar, Riddhi G.; Ong, Joon Faii; Levy, Oren; Karp, Jeffrey M.

    2014-04-01

    Inadequate immunomodulatory potency of mesenchymal stem cells (MSC) may limit their therapeutic efficacy. We report glucocorticoid steroids augment MSC expression and activity of indoleamine-2,3-dioxygenase (IDO), a primary mediator of MSC immunomodulatory function. This effect depends on signaling through the glucocorticoid receptor and is mediated through up-regulation of FOXO3. Treatment of MSCs with glucocorticoids, budesonide or dexamethasone, enhanced IDO expression following IFN-γ stimulation in multiple donors and was able to restore IDO expression in over-passaged MSCs. As IDO enhancement was most notable when cells were continuously exposed to budesonide, we engineered MSC with budesonide loaded PLGA microparticles. MSC efficiently internalized budesonide microparticles and exhibited 4-fold enhanced IDO activity compared to budesonide preconditioned and naïve MSC, resulting in a 2-fold improvement in suppression of stimulated peripheral blood mononuclear cells in an IDO-dependent manner. Thus, the augmentation of MSC immune modulation may abrogate challenges associated with inadequate potency and enhance their therapeutic efficacy.

  16. Effect of human umbilical cord mesenchymal stem cell-secretion on proliferation and apoptosis in hepatocytes%人脐带间充质干细胞分泌物对肝细胞增殖和凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    黎娇; 朱争艳; 杜智; 骆莹; 王鹏; 高英堂

    2010-01-01

    目的 探讨人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,HUC MSC)旁分泌物质在体外对肝细胞再生和凋亡的影响.方法 利用Ⅳ型胶原酶和胰酶消化法从脐带中分离间充质干细胞,制备含有HUCMSC旁分泌物质的条件培养基(mesenchymal stem cells-conditioned medium,MSC-CM),采用低浓度胶原酶原位循环灌流法分离肝细胞.试验分为对照组、2%MSC-CM组和8%MSC-CM组三组.采用MTT比色法观察不同浓度MSC-CM对正常肝细胞增殖的影响.测定上清中尿素、白蛋白的含量,观察不同浓度MSC-CM对肝细胞功能的影响.利用放线菌素D和肿瘤坏死因子α诱导肝细胞凋亡,采用细胞活性分析试剂盒检测不同浓度MSC-CM对肝细胞凋亡的影响.结果 与对照组比较,2%MSC-CM组吸光度(A)540nm值(P<0.01)以及上清尿素和白蛋白含量显著升高(P<0.01),肝细胞存活率增加(P<0.05);8%MSC-CM组与对照组无显著差异.结论 低浓度的MSC-CM在体外可以刺激正常肝细胞再生,抑制受损肝细胞凋亡,改善肝细胞功能.%Objective To investigate the effect of human umbilical cord mesenchymal stem cell paracrine substance on proliferation and apoptosis of liver cells in vitro. Methods Mesenchymal stem cells (MSC)were separated from human umbilical cord with type Ⅳ collagenase and trypsogen digestion method and cultured in vitro. The human umbilical cord mesenchymal stem cells-conditioned medium(MSC-CM) which contain paracrine substance of human umbilical cord mesenchymal stem cells (HUCMSC) was prepared. Hepatocytes were isolated from SD rats by low concentration collagenase perfusion procedure. There were three groups in the experiment, control group, 2% MSC-CM group and 8% MSC-CM group. The proliferation of normal hepatocytes were assayed with MTT method. We detected the urea and albumin level in culture supernatant to assay the hepatocyte function under different concentration MSC-CM. Hepatocytes were

  17. Micromass co-culture of human articular chondrocytes and human bone marrow mesenchymal stem cells to investigate stable neocartilage tissue formation in vitro

    Directory of Open Access Journals (Sweden)

    S Giovannini

    2010-10-01

    Full Text Available Cell therapies for articular cartilage defects rely on expanded chondrocytes. Mesenchymal stem cells (MSC represent an alternative cell source should their hypertrophic differentiation pathway be prevented. Possible cellular instruction between human articular chondrocytes (HAC and human bone marrow MSC was investigated in micromass pellets. HAC and MSC were mixed in different percentages or incubated individually in pellets for 3 or 6 weeks with and without TGF-beta1 and dexamethasone (±T±D as chondrogenic factors. Collagen II, collagen X and S100 protein expression were assessed using immunohistochemistry. Proteoglycan synthesis was evaluated applying the Bern score and quantified using dimethylmethylene blue dye binding assay. Alkaline phosphatase activity (ALP was detected on cryosections and soluble ALP measured in pellet supernatants. HAC alone generated hyaline-like discs, while MSC formed spheroid pellets in ±T±D. Co-cultured pellets changed from disc to spheroid shape with decreasing number of HAC, and displayed random cell distribution. In -T-D, HAC expressed S100, produced GAG and collagen II, and formed lacunae, while MSC did not produce any cartilage-specific proteins. Based on GAG, collagen type II and S100 expression chondrogenic differentiation occurred in -T-D MSC co-cultures. However, quantitative experimental GAG and DNA values did not differ from predicted values, suggesting only HAC contribution to GAG production. MSC produced cartilage-specific matrix only in +T+D but underwent hypertrophy in all pellet cultures. In summary, influence of HAC on MSC was restricted to early signs of neochondrogenesis. However, MSC did not contribute to the proteoglycan deposition, and HAC could not prevent hypertrophy of MSC induced by chondrogenic stimuli.

  18. Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Acute Lung Injury and Other Inflammatory Lung Diseases

    Science.gov (United States)

    Monsel, Antoine; Zhu, Ying-gang; Gudapati, Varun; Lim, Hyungsun; Lee, Jae W.

    2017-01-01

    Introduction Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. Areas covered The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases. Expert opinion While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification. PMID:27011289

  19. Partial Purification and Characterization of a Heat Stable α-Amylase from a Thermophilic Actinobacteria, Streptomyces sp. MSC702

    Directory of Open Access Journals (Sweden)

    Renu Singh

    2014-01-01

    Full Text Available A partial purification and biochemical characterization of the α-amylase from Streptomyces sp. MSC702 were carried out in this study. The optimum operational conditions for enzyme substrate reaction for amylolytic enzyme activity from the strain were evaluated. The optimum pH, temperature, and incubation period for assaying the enzyme were observed to be 5.0, 55°C, and 30 min, respectively. The extracellular extract was concentrated using ammonium sulfate precipitation. It was stable in the presence of metal ions (5 mM such as K+, Co2+, and Mo2+, whereas Pb2+, Mn2+, Mg2+, Cu2+, Zn2+, Ba2+, Ca2+, Hg2+, Sn2+, Cr3+, Al3+, Ag+, and Fe2+ were found to have inhibitory effects. The enzyme activity was also unstable in the presence of 1% Triton X-100, 1% Tween 80, 5 mM sodium lauryl sulphate, 1% glycerol, 5 mM EDTA, and 5 mM denaturant urea. At temperature 60°C and pH 5.0, the enzyme stability was maximum. α-amylase retained 100% and 34.18% stability for 1 h and 4 h, respectively, at 60°C (pH 7.0. The enzyme exhibited a half-life of 195 min at 60°C temperature. The analysis of kinetic showed that the enzyme has Km of 2.4 mg/mL and Vmax of 21853.0 μmol/min/mg for soluble potato starch. The results indicate that the enzyme reflects their potentiality towards industrial utilization.

  20. Purification of the small mechanosensitive channel of Escherichia coli (MscS): the subunit structure, conduction, and gating characteristics in liposomes

    Science.gov (United States)

    Sukharev, Sergei

    2002-01-01

    The small mechanosensitive channel, MscS, is a part of the turgor-driven solute efflux system that protects bacteria from lysis in the event of osmotic downshift. It has been identified in Escherichia coli as a product of the orphan yggB gene, now called mscS (Levina et al., 1999, EMBO J. 18:1730). Here I show that that the isolated 31-kDa MscS protein is sufficient to form a functional mechanosensitive channel gated directly by tension in the lipid bilayer. MscS-6His complexes purified in the presence of octylglucoside and lipids migrate in a high-resolution gel-filtration column as particles of approximately 200 kDa. Consistent with that, the protein cross-linking patterns predict a hexamer. The channel reconstituted in soybean asolectin liposomes was activated by pressures of 20-60 mm Hg and displayed the same asymmetric I-V curve and slight anionic preference as in situ. At the same time, the single-channel conductance is proportional to the buffer conductivity in a wide range of salt concentrations. The rate of channel activation in response to increasing pressure gradient across the patch was slower than the rate of closure in response to decreasing steps of pressure gradient. Therefore, the open probability curves were recorded with descending series of pressures. Determination of the curvature of patches by video imaging permitted measurements of the channel activity as a function of membrane tension (gamma). Po(gamma) curves had the midpoint at 5.5 +/- 0.1 dyne/cm and gave estimates for the energy of opening DeltaG = 11.4 +/- 0.5 kT, and the transition-related area change DeltaA = 8.4 +/- 0.4 nm(2) when fitted with a two-state Boltzmann model. The correspondence between channel properties in the native and reconstituted systems is discussed.

  1. Neuronal Analogues of Conditioning Paradigms

    Science.gov (United States)

    1984-04-24

    Although the mechanisms of interneuronal communication have been well established, the changes underlying most forms of learning have thus far eluded...stimulating electrodes on one of the connectives was adjusted so as to produce a small excitatory postsynaptic potential ( EPSP ) in the impaled cell...two stimuli would constitute a neuronal analogue of conditioning by producing an increased EPSP in response to the test stimulus alone. If so, then

  2. Cnn: a Paradigm for Complexity

    Science.gov (United States)

    Chua, Leon O.

    The following sections are included: * What is a CNN? * Part I: Standard CNNs * Standard CNNs are uniquely specified by CNN genes * Oscillations and chaos from standard CNNs * Complete stability criteria for standard CNNs * Bistable criterion * Coding the CNN gene * Edge detection CNN * Corner detection CNN * A gallery of basic CNN genes * Does there exist a CNN gene for solving Minsky's global connectivity problem? * Decoding the CNN gene * Examples of input-output CNN operators * Uncoupled CNN genes * Boolean CNN genes and truth tables * What task can an uncoupled Boolean CNN gene Perform? * Bifurcation of CNN genes * The game-of-life CNN gene * The CNN universal machine * Generalized cellular automata * A glimpse at some real-world CNN applications * Part II: Autonomous CNNs * Pattern formation in standard CNNs * Characterization of stable equilibria * The dynamics of pattern formation * CNN pattern formation in biology and physics * Pattern formation in reaction-diffusion CNNs * Nonlinear waves in reaction-diffusion CNNs * Simulating nonlinear PDEs via autonomous CNNs * Part III: Local Activity: The Genesis of Complexity * Transistors and local activity: What do they have to common? * Nonlinear circuit models for reaction-diffusion CNNs * What is local activity? * Cell equilibrium points * Local state equations and local power flows * Local activity in reaction-diffusion CNN cells * Testing for local activity * Testing one-port CNN cells for local activity * Testing two-port CNN cells for local activity * Why is local activity necessary for pattern formation? * How to choose locally-active CNN parameters? * Local activity and stability are different concepts * The local activity dogma

  3. Molecular characterisation of stromal populations derived from human embryonic stem cells

    DEFF Research Database (Denmark)

    Harkness, L.; Twine, N. A.; Abu Dawud, R.;

    2015-01-01

    of hESC-stromal and immortalised BM-hMSC cells (hMSC-TERT). Of the 7379 genes expressed above baseline, only 9.3% of genes were differentially expressed between undifferentiated hESC-stromal and BM-hMSC. Following ex vivo osteoblast induction, 665 and 695 genes exhibited >. 2-fold change (FC) in h......ESC-stromal and BM-hMSC, respectively with 172 genes common to both cell types. Functional annotation of significantly changing genes revealed similarities in gene ontology between the two cell types. Interestingly, genes in categories of cell adhesion/motility and epithelial-mesenchymal transition (EMT) were highly...... enriched in hESC-stromal whereas genes associated with cell cycle processes were enriched in hMSC-TERT. This data suggests that while hESC-stromal cells exhibit a similar molecular phenotype to hMSC-TERT, differences exist that can be explained by ontological differences between these two cell types. h...

  4. Paradigm formation and paradigm change in the EU’s Stability and Growth Pact

    NARCIS (Netherlands)

    Princen, Sebastiaan; van Esch, Femke

    2016-01-01

    This article analyses whether the European Union’s (EU) Stability and Growth Pact (SGP) has been underpinned by a policy paradigm. In doing so, it seeks to contribute to the debate on the existence and importance of paradigms in policy-making. It uses a causal mapping technique to reconstruct the be

  5. ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

    Directory of Open Access Journals (Sweden)

    D. D. Miniaeva

    2014-06-01

    Full Text Available This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism. The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, targets, tools, processes. Results of research show that the beginning of the XXI century is distinguished by the development of new types of political concepts that explain interaction of elements in modern international relations in the area of environmental protection. The reason of these changes lies in the phenomena of environmentalism integration into Three paradigms of international relations. However, we cannot say that any of the examined paradigms accumulated all features of environmentalism without their modification. Better to say, it's rather similar to adaptation of environmental ideas. Therefore, to understand modern international relations processes, it is necessary to take into account their environmental element. Purchase on Elibrary.ru > Buy nowDOI: http://dx.doi.org/10.12731/2070-7568-2014-3-4

  6. Spatial organization of mesenchymal stem cells in vitro--results from a new individual cell-based model with podia.

    Directory of Open Access Journals (Sweden)

    Martin Hoffmann

    Full Text Available Therapeutic application of mesenchymal stem cells (MSC requires their extensive in vitro expansion. MSC in culture typically grow to confluence within a few weeks. They show spindle-shaped fibroblastoid morphology and align to each other in characteristic spatial patterns at high cell density. We present an individual cell-based model (IBM that is able to quantitatively describe the spatio-temporal organization of MSC in culture. Our model substantially improves on previous models by explicitly representing cell podia and their dynamics. It employs podia-generated forces for cell movement and adjusts cell behavior in response to cell density. At the same time, it is simple enough to simulate thousands of cells with reasonable computational effort. Experimental sheep MSC cultures were monitored under standard conditions. Automated image analysis was used to determine the location and orientation of individual cells. Our simulations quantitatively reproduced the observed growth dynamics and cell-cell alignment assuming cell density-dependent proliferation, migration, and morphology. In addition to cell growth on plain substrates our model captured cell alignment on micro-structured surfaces. We propose a specific surface micro-structure that according to our simulations can substantially enlarge cell culture harvest. The 'tool box' of cell migratory behavior newly introduced in this study significantly enhances the bandwidth of IBM. Our approach is capable of accommodating individual cell behavior and collective cell dynamics of a variety of cell types and tissues in computational systems biology.

  7. Encapsulated glucagon-like peptide-1-producing mesenchymal stem cells have a beneficial effect on failing pig hearts

    DEFF Research Database (Denmark)

    Wright, Elizabeth J; Farrell, Kelly A; Malik, Nadim;

    2012-01-01

    -life in vivo. The effects of prolonged GLP-1 delivery from stromal cells post-MI were evaluated in a porcine model. Human mesenchymal stem cells immortalized and engineered to produce a GLP-1 fusion protein were encapsulated in alginate (bead-GLP-1 MSC) and delivered to coronary artery branches. Control groups...... and showed decreased infarction area compared with controls. Histological analysis showed reduced inflammation and a trend toward reduced apoptosis in the infarct zone. Increased collagen but fewer myofibroblasts were observed in infarcts of the bead-GLP-1 MSC and bead-MSC groups, and significantly more...

  8. A Paradigm for Spreadsheet Engineering Methodologies

    CERN Document Server

    Grossman, Thomas A

    2008-01-01

    Spreadsheet engineering methodologies are diverse and sometimes contradictory. It is difficult for spreadsheet developers to identify a spreadsheet engineering methodology that is appropriate for their class of spreadsheet, with its unique combination of goals, type of problem, and available time and resources. There is a lack of well-organized, proven methodologies with known costs and benefits for well-defined spreadsheet classes. It is difficult to compare and critically evaluate methodologies. We present a paradigm for organizing and interpreting spreadsheet engineering recommendations. It systematically addresses the myriad choices made when developing a spreadsheet, and explicitly considers resource constraints and other development parameters. This paradigm provides a framework for evaluation, comparison, and selection of methodologies, and a list of essential elements for developers or codifiers of new methodologies. This paradigm identifies gaps in our knowledge that merit further research.

  9. Mesenchymal Stem Cell Conditioned Medium Promotes Proliferation and Migration of Alveolar Epithelial Cells under Septic Conditions In Vitro via the JNK-P38 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jie Chen

    2015-11-01

    Full Text Available Background/Aims: Mesenchymal stem cell (MSC based therapies may be useful for treating acute respiratory distress syndrome (ARDS, but the underlying mechanisms are incompletely understood. We investigated the impact of human umbilical cord Wharton's jelly-derived MSC (hUC-MSC secreted factors on alveolar epithelial cells under septic conditions and determined the relevant intracellular signaling pathways. Methods: Human alveolar epithelial cells (AEC and primary human small airway epithelial cells (SAEC were subjected to lipopolysaccharide (LPS with or without the presence of hUC-MSC-conditioned medium (CM. Proliferation and migration of AEC and SAEC were determined via an MTT assay, a wound healing assay and a transwell migration assay (only for AEC. Protein phosphorylation was determined by western blot and the experiments were repeated in presence of small-molecule inhibitors. The hMSC-secretory proteins were identified by LC-MS/MS mass spectrometry. Results: MSC-CM enhanced proliferation and migration. Activation of JNK and P38, but not ERK, was required for the proliferation and migration of AEC and SAEC. Pretreatment of AEC or SAEC with SP600125, an inhibitor of JNK1 or SB200358, an inhibitor of P38, significantly reduced cell proliferation and migration. An array of proteins including TGF-beta receptor type-1, TGF-beta receptor type-2, Ras-related C3 botulinum toxin substrate 1 and Ras-related C3 botulinum toxin substrate 2 which influencing the proliferation and migration of AEC and SAEC were detected in MSC-CM. Conclusion: Our data suggest MSC promote epithelial cell repair through releasing a repertoire of paracrine factors via activation of JNK and P38 MAPK.

  10. Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization

    DEFF Research Database (Denmark)

    Elsafadi, E; Manikandan, M; Dawud, RA;

    2016-01-01

    bone marrow-derived stromal (skeletal) stem cells (hMSC). siRNA-mediated gene silencing of TAGLN impaired lineage differentiation into osteoblasts and adipocytes but enhanced cell proliferation. Additional functional studies revealed that TAGLN deficiency impaired hMSC cell motility and in vitro...... transwell cell migration. On the other hand, TAGLN overexpression reduced hMSC cell proliferation, but enhanced cell migration, osteoblastic and adipocytic differentiation, and in vivo bone formation. In addition, deficiency or overexpression of TAGLN in hMSC was associated with significant changes...... in cellular and nuclear morphology and cytoplasmic organelle composition as demonstrated by high content imaging and transmission electron microscopy that revealed pronounced alterations in the distribution of the actin filament and changes in cytoskeletal organization. Molecular signature of TAGLN...

  11. Multi-stage continuous high cell density culture systems: a review.

    Science.gov (United States)

    Chang, Ho Nam; Jung, Kwonsu; Choi, Jin-Dal-Rae; Lee, Joon Chul; Woo, Hee-Chul

    2014-01-01

    A multi-stage continuous high cell density culture (MSC-HCDC) system makes it possible to achieve high productivity together with high product titer of many bioproducts. For long-term continuous operation of MSC-HCDC systems, the cell retention time and hydraulic retention time must be decoupled and strains (bacteria, yeast, plant, and animal cells) must be stable. MSC-HCDC systems are suitable for low-value high-volume extracellular products such as fuel ethanol, lactic acid or volatile fatty acids, and high-value products such as monoclonal antibodies as well as intracellular products such as polyhydroxybutyric acid (PHB), microbial lipids or a number of therapeutics. Better understanding of the fermentation kinetics of a specific product and reliable high-density culture methods for the product-generating microorganisms will facilitate timely industrialization of MSC-HCDC systems for products that are currently obtained in fed-batch bioreactors.

  12. Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy

    Science.gov (United States)

    Pashoutan Sarvar, Davod; Shamsasenjan, Karim; Akbarzadehlaleh, Parvin

    2016-01-01

    Mesenchymal stromal/stem cells (MSCs) are involved in tissue homeostasis through direct cell-to-cell interaction, as well as secretion of soluble factors. Exosomes are the sort of soluble biological mediators that obtained from MSCs cultured media in vitro. MSC-derived exosomes (MSC-DEs) which produced under physiological or pathological conditions are central mediators of intercellular communications by conveying proteins, lipids, mRNAs, siRNA, ribosomal RNAs and miRNAs to the neighbor or distant cells. MSC-DEs have been tested in various disease models, and the results have revealed that their functions are similar to those of MSCs. They have the supportive functions in organisms such as repairing tissue damages, suppressing inflammatory responses, and modulating the immune system. MSC-DEs are of great interest in the scope of regenerative medicine because of their unique capacity to the regeneration of the damaged tissues, and the present paper aims to introduce MSC-DEs as a novel hope in cell-free therapy.

  13. Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors.

    Science.gov (United States)

    Rafiq, Qasim A; Coopman, Karen; Nienow, Alvin W; Hewitt, Christopher J

    2016-03-01

    Production of human mesenchymal stem cells for allogeneic cell therapies requires scalable, cost-effective manufacturing processes. Microcarriers enable the culture of anchorage-dependent cells in stirred-tank bioreactors. However, no robust, transferable methodology for microcarrier selection exists, with studies providing little or no reason explaining why a microcarrier was employed. We systematically evaluated 13 microcarriers for human bone marrow-derived MSC (hBM-MSCs) expansion from three donors to establish a reproducible and transferable methodology for microcarrier selection. Monolayer studies demonstrated input cell line variability with respect to growth kinetics and metabolite flux. HBM-MSC1 underwent more cumulative population doublings over three passages in comparison to hBM-MSC2 and hBM-MSC3. In 100 mL spinner flasks, agitated conditions were significantly better than static conditions, irrespective of donor, and relative microcarrier performance was identical where the same microcarriers outperformed others with respect to growth kinetics and metabolite flux. Relative growth kinetics between donor cells on the microcarriers were the same as the monolayer study. Plastic microcarriers were selected as the optimal microcarrier for hBM-MSC expansion. HBM-MSCs were successfully harvested and characterised, demonstrating hBM-MSC immunophenotype and differentiation capacity. This approach provides a systematic method for microcarrier selection, and the findings identify potentially significant bioprocessing implications for microcarrier-based allogeneic cell therapy manufacture.

  14. Mesenchymal stem cells do not prevent antibody responses against human α-L-iduronidase when used to treat mucopolysaccharidosis type I.

    Directory of Open Access Journals (Sweden)

    Priscila Keiko Matsumoto Martin

    Full Text Available Mucopolysaccharidosis type I (MPSI is an autosomal recessive disease that leads to systemic lysosomal storage, which is caused by the absence of α-L-iduronidase (IDUA. Enzyme replacement therapy is recognized as the best therapeutic option for MPSI; however, high titers of anti-IDUA antibody have frequently been observed. Due to the immunosuppressant properties of MSC, we hypothesized that MSC modified with the IDUA gene would be able to produce IDUA for a long period of time. Sleeping Beauty transposon vectors were used to modify MSC because these are basically less-immunogenic plasmids. For cell transplantation, 4×10(6 MSC-KO-IDUA cells (MSC from KO mice modified with IDUA were injected into the peritoneum of KO-mice three times over intervals of more than one month. The total IDUA activities from MSC-KO-IDUA before cell transplantation were 9.6, 120 and 179 U for the first, second and third injections, respectively. Only after the second cell transplantation, more than one unit of IDUA activity was detected in the blood of 3 mice for 2 days. After the third cell transplantation, a high titer of anti-IDUA antibody was detected in all of the treated mice. Anti-IDUA antibody response was also detected in C57Bl/6 mice treated with MSC-WT-IDUA. The antibody titers were high and comparable to mice that were immunized by electroporation. MSC-transplanted mice had high levels of TNF-alpha and infiltrates in the renal glomeruli. The spreading of the transplanted MSC into the peritoneum of other organs was confirmed after injection of 111In-labeled MSC. In conclusion, the antibody response against IDUA could not be avoided by MSC. On the contrary, these cells worked as an adjuvant that favored IDUA immunization. Therefore, the humoral immunosuppressant property of MSC is questionable and indicates the danger of using MSC as a source for the production of exogenous proteins to treat monogenic diseases.

  15. Paradigms for Realizing Machine Learning Algorithms.

    Science.gov (United States)

    Agneeswaran, Vijay Srinivas; Tonpay, Pranay; Tiwary, Jayati

    2013-12-01

    The article explains the three generations of machine learning algorithms-with all three trying to operate on big data. The first generation tools are SAS, SPSS, etc., while second generation realizations include Mahout and RapidMiner (that work over Hadoop), and the third generation paradigms include Spark and GraphLab, among others. The essence of the article is that for a number of machine learning algorithms, it is important to look beyond the Hadoop's Map-Reduce paradigm in order to make them work on big data. A number of promising contenders have emerged in the third generation that can be exploited to realize deep analytics on big data.

  16. International business and the eclectic paradigm

    DEFF Research Database (Denmark)

    The eclectic paradigm has become the dominant theoretical basis in the study of international business, multinational corporations and internationalization since 1980. However, developments such as economic globalization and the subsequent growth of global and alliance capitalism have fundamentally......, finance, evolutionary economics, resource-based theory or strategic management? Can it be utilized to explain new developments in international business and economics? Do these require new ideas and concepts to be integrated within the eclectic paradigm? What are the new challenges to which international...... business theorizing must respond?...

  17. Convergence Analysis of a Domain Decomposition Paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Bank, R E; Vassilevski, P S

    2006-06-12

    We describe a domain decomposition algorithm for use in several variants of the parallel adaptive meshing paradigm of Bank and Holst. This algorithm has low communication, makes extensive use of existing sequential solvers, and exploits in several important ways data generated as part of the adaptive meshing paradigm. We show that for an idealized version of the algorithm, the rate of convergence is independent of both the global problem size N and the number of subdomains p used in the domain decomposition partition. Numerical examples illustrate the effectiveness of the procedure.

  18. Gene expression changes in the injured spinal cord following transplantation of mesenchymal stem cells or olfactory ensheathing cells.

    Directory of Open Access Journals (Sweden)

    Abel Torres-Espín

    Full Text Available Transplantation of bone marrow derived mesenchymal stromal cells (MSC or olfactory ensheathing cells (OEC have demonstrated beneficial effects after spinal cord injury (SCI, providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI.

  19. Adipose Mesenchymal Stem Cell Secretome Modulated in Hypoxia for Remodeling of Radiation-Induced Salivary Gland Damage.

    Directory of Open Access Journals (Sweden)

    Hye-Young An

    Full Text Available This study was conducted to determine whether a secretome from mesenchymal stem cells (MSC modulated by hypoxic conditions to contain therapeutic factors contributes to salivary gland (SG tissue remodeling and has the potential to improve irradiation (IR-induced salivary hypofunction in a mouse model.Human adipose mesenchymal stem cells (hAdMSC were isolated, expanded, and exposed to hypoxic conditions (O2 < 5%. The hypoxia-conditioned medium was then filtered to a high molecular weight fraction and prepared as a hAdMSC secretome. The hAdMSC secretome was subsequently infused into the tail vein of C3H mice immediately after local IR once a day for seven consecutive days. The control group received equal volume (500 μL of vehicle (PBS only. SG function and structural tissue remodeling by the hAdMSC secretome were investigated. Human parotid epithelial cells (HPEC were obtained, expanded in vitro, and then irradiated and treated with either the hypoxia-conditioned medium or a normoxic control medium. Cell proliferation and IR-induced cell death were examined to determine the mechanism by which the hAdMSC secretome exerted its effects.The conditioned hAdMSC secretome contained high levels of GM-CSF, VEGF, IL-6, and IGF-1. Repeated systemic infusion with the hAdMSC secretome resulted in improved salivation capacity and increased levels of salivary proteins, including amylase and EGF, relative to the PBS group. The microscopic structural integrity of SG was maintained and salivary epithelial (AQP-5, endothelial (CD31, myoepithelial (α-SMA and SG progenitor cells (c-Kit were successfully protected from radiation damage and remodeled. The hAdMSC secretome strongly induced proliferation of HPEC and led to a significant decrease in cell death in vivo and in vitro. Moreover, the anti-apoptotic effects of the hAdMSC secretome were found to be promoted after hypoxia-preconditioning relative to normoxia-cultured hAdMSC secretome.These results show that the

  20. Effects of intra-articular injection of mesenchymal stem cells associated with platelet-rich plasma in a rabbit model of osteoarthritis.

    Science.gov (United States)

    Hermeto, L C; DeRossi, R; Oliveira, R J; Pesarini, J R; Antoniolli-Silva, A C M B; Jardim, P H A; Santana, A E; Deffune, E; Rinaldi, J C; Justulin, L A

    2016-09-02

    The current study aims to evaluate the macroscopic and histological effects of autologous mesenchymal stem cells (MSC) and platelet-rich plasma on knee articular cartilage regeneration in an experimental model of osteoarthritis. Twenty-four rabbits were randomly divided into four groups: control group, platelet-rich plasma group, autologous MSC undifferentiated group, and autologous MSC differentiated into chondrocyte group. Collagenase solution was used to induce osteoarthritis, and treatments were applied to each group at 6 weeks following osteoarthritis induction. After 60 days of therapy, the animals were euthanized and the articular surfaces were subjected to macroscopic and histological evaluations. The adipogenic, chondrogenic, and osteogenic differentiation potentials of MSCs were evaluated. Macroscopic and histological examinations revealed improved tissue repair in the MSC-treated groups. However, no difference was found between MSC-differentiated and undifferentiated chondrocytes. We found that MSCs derived from adipose tissue and platelet-rich plasma were associated with beneficial effects in articular cartilage regeneration during experimental osteoarthritis.

  1. Efficacy of a mesenchymal stem cell loaded surgical mesh for tendon repair in rats

    OpenAIRE

    Schon, Lew C.; Gill, Nicholas; Thorpe, Margaret; Davis, Joel; Nadaud, Joshua; Kim, Jooyoung; Molligan, Jeremy; Zhang, Zijun

    2014-01-01

    Objectives The purpose of this study was to investigate the efficacy of a composite surgical mesh for delivery of mesenchymal stem cells (MSCs) in tendon repair. Methods The MSC-loaded mesh composed of a piece of conventional surgical mesh and a layer of scaffold, which supported MSC-embedded alginate gel. A 3-mm defect was surgically created at the Achilles tendon-gastrocnemius/soleus junction in 30 rats. The tendon defects were repaired with either 1) MSC-loaded mesh; or 2) surgical mesh on...

  2. A fat option for the pig: Hepatocytic differentiated mesenchymal stem cells for translational research

    Energy Technology Data Exchange (ETDEWEB)

    Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Tautenhahn, Hans-Michael, E-mail: hans-michael.tautenhahn@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103 (Germany); Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Dollinger, Matthias, E-mail: matthias.dollinger@uniklinik-ulm.de [University Hospital Ulm, First Department of Medicine, Albert-Einstein-Allee 23, Ulm D-89081 (Germany); Christ, Bruno, E-mail: bruno.christ@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103 (Germany)

    2014-02-15

    Study background: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention in the pig model. Methods: Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes. Results: MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue. Conclusion: The hepatocyte

  3. Isolation and Characterization of Multipotential Mesenchymal Stromal Cells from Congenital Pseudoarthrosis of the Tibia: Case Report.

    Science.gov (United States)

    Diaz-Solano, Dylana; Wittig, Olga; Mota, Jose D; Cardier, Jose E

    2015-10-01

    Congenital pseudoarthrosis of the tibia (CPT) is an uncommon disease whose etiology and pathogenesis is unknown. Several evidences suggest that decreased osteogenic capacities, impaired local vascularization, and microenvironment alterations may play a role in the pathogenesis of CPT. Additionally, it is not clear if the pathogenesis of this disease is related to the absence of cells with osteogenic capacity of differentiation. In this work, a two-year-old patient diagnosed with CPT underwent an orthopedic surgery to promote bone union in a pseudoarthrosis lesion. Tissue from CPT lesion was excised, and histological evaluation and tissue culture were performed. Histologic analysis of the soft CPT lesion showed the presence of highly cellular fibrous tissue, vascularization, and abundant extracellular matrix. Fusiform cells of mesenchymal appearance were observed but osteoblasts, osteoclasts, chondrocytes, and adipose cells were not found. There was no evidence of osteogenesis. CPT tissue cultured as explants showed, after one month of culture, evidence of osteogenesis, chondrogenesis, and adipogenesis. Cells isolated from explants of CPT tissue showed a fibroblast-like morphology and expressed the mesenchymal stromal cell (MSC) markers: CD105, CD73, and CD90 (CPT-MSC). Functional analysis showed that CPT-MSC differentiate, in vitro, into osteogenic, chondrogenic, and adipocytic cells. CPT-MSC expressed osteocalcin and agrecan. CPT-MSC produced collagen in the presence of ascorbic acid. MSC from BM of normal individuals were used as control. In summary, our results indicate that CPT tissue contains MSC with osteogenic capacity of differentiation. It is possible that CPT microenvironment may contribute to impair the osteogenic capacity of differentiation of CPT-MSC.

  4. Role of mesenchymal stem cell-derived fibrinolytic factor in tissue regeneration and cancer progression.

    Science.gov (United States)

    Heissig, Beate; Dhahri, Douaa; Eiamboonsert, Salita; Salama, Yousef; Shimazu, Hiroshi; Munakata, Shinya; Hattori, Koichi

    2015-12-01

    Tissue regeneration during wound healing or cancer growth and progression depends on the establishment of a cellular microenvironment. Mesenchymal stem cells (MSC) are part of this cellular microenvironment, where they functionally modulate cell homing, angiogenesis, and immune modulation. MSC recruitment involves detachment of these cells from their niche, and finally MSC migration into their preferred niches; the wounded area, the tumor bed, and the BM, just to name a few. During this recruitment phase, focal proteolysis disrupts the extracellular matrix (ECM) architecture, breaks cell-matrix interactions with receptors, and integrins, and causes the release of bioactive fragments from ECM molecules. MSC produce a broad array of proteases, promoting remodeling of the surrounding ECM through proteolytic mechanisms. The fibrinolytic system, with its main player plasmin, plays a crucial role in cell migration, growth factor bioavailability, and the regulation of other protease systems during inflammation, tissue regeneration, and cancer. Key components of the fibrinolytic cascade, including the urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), are expressed in MSC. This review will introduce general functional properties of the fibrinolytic system, which go beyond its known function of fibrin clot dissolution (fibrinolysis). We will focus on the role of the fibrinolytic system for MSC biology, summarizing our current understanding of the role of the fibrinolytic system for MSC recruitment and the functional consequences for tissue regeneration and cancer. Aspects of MSC origin, maintenance, and the mechanisms by which these cells contribute to altered protease activity in the microenvironment under normal and pathological conditions will also be discussed.

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

    Directory of Open Access Journals (Sweden)

    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

  6. Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site

    Directory of Open Access Journals (Sweden)

    Zhifa Wang

    2016-02-01

    Full Text Available To determine the effect of adipose-derived stem cells (ADSCs added to bone marrow-derived mesenchymal stem cell (MSC sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration.

  7. 06472 Abstracts Collection - XQuery Implementation Paradigms

    NARCIS (Netherlands)

    Boncz, Peter A.; Grust, Torsten; Siméon, Jerome; Keulen, van Maurice; Boncz, P.A.; Grust, T.; Siméon, J.; Keulen, van M.

    2007-01-01

    From 19.11.2006 to 22.11.2006, the Dagstuhl Seminar 06472 ``XQuery Implementation Paradigms'' was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were disc

  8. 06472 Abstracts Collection - XQuery Implementation Paradigms

    NARCIS (Netherlands)

    Boncz, P.A.; Grust, T.; Siméon, J.; Keulen, M. van

    2007-01-01

    From 19.11.2006 to 22.11.2006, the Dagstuhl Seminar 06472 "XQuery Implementation Paradigms" was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were discus

  9. Reinforcing the Afrocentric Paradigm: A Theoretical Project

    Science.gov (United States)

    Sams, Timothy E.

    2010-01-01

    Thomas Kuhn's 1962 groundbreaking work, "The Scientific Revolution," established the process for creating, and the components of, a disciplinary paradigm. This "scientific revolution" has evolved to become the standard for determining a field's claim to disciplinary status. In 2001 and 2003, Ama Mazama, used Kuhn's model to establish the…

  10. Haptics in computer music : a paradigm shift

    CERN Document Server

    Castagné, Nicolas; Florens, Jean-Loup; Luciani, Annie

    2010-01-01

    With an historical point of view combined with a bibliographic overview, the article discusses the idea that haptic force feedback transducers correspond with a paradigm shift in our real-time tools for creating music. So doing, il shows that computer music may be regarded as a major field of research and application for haptics.

  11. A new paradigm for doing Reformed dogmatics

    Directory of Open Access Journals (Sweden)

    G. J. Spykman

    1992-06-01

    Full Text Available When discussing Reformational Theology: A New Paradigm for Doing Dogmatics some people may call it my opus magnum. Perhaps time 'will tell. The book has only recently - early 1992 - entered the marketplace of theological ideas. How critic readers and reviewers respond will go a long way toward settling the case.

  12. Challenging paradigms in estuarine ecology and management

    Science.gov (United States)

    Elliott, M.; Whitfield, A. K.

    2011-10-01

    For many years, estuarine science has been the 'poor relation' in aquatic research - freshwater scientists ignored estuaries as they tended to get confused by salt and tides, and marine scientists were more preoccupied by large open systems. Estuaries were merely regarded by each group as either river mouths or sea inlets respectively. For the past four decades, however, estuaries (and other transitional waters) have been regarded as being ecosystems in their own right. Although often not termed as such, this has led to paradigms being generated to summarise estuarine structure and functioning and which relate to both the natural science and management of these systems. This paper defines, details and affirms these paradigms that can be grouped into those covering firstly the science (definitions, scales, linkages, productivity, tolerances and variability) and secondly the management (pressures, valuation, health and services) of estuaries. The more 'science' orientated paradigms incorporate the development and types of ecotones, the nature of stressed and variable systems (with specific reference to resilience and redundancy), the relationship between generalists and specialists produced by environmental tolerance, the relevance of scale in relation to functioning and connectivity, the sources of production and degree of productivity, the biodiversity-ecosystem functioning and the stress-subsidy debates. The more 'management' targeted paradigms include the development and effects of exogenic unmanaged pressures and endogenic managed pressures, the perception of health and the ability to manage estuaries (related to internal and external influences), and the influence of all of these on the production of ecosystem services and societal benefits.

  13. Production planning development and paradigm integration

    Directory of Open Access Journals (Sweden)

    Galina Ledneva

    2009-12-01

    Full Text Available The paper reviews principles of different concepts of enterprise management including a theory of constrains, a Balanced Scorecard, lean production, Six Sigma. The authors believe that creating some mix or integration of these paradigms can bring extraordinary effect for production management. As example the modified Balanced Scorecard based on constraints and its application on Magnitorsk metallurgical enterprise in Russia is described.

  14. About the Consept of Pedagogic Paradigm

    Directory of Open Access Journals (Sweden)

    V. A. Testov

    2012-01-01

    Full Text Available The paradigm concept, essential for comprehension and analysis of the science history, is used quite freely and easily in educational sphere nowadays when some authors discuss their views, theories and developments referring to a new paradigm. Consequently, in pedagogy, there is an illusion of pseudo-paradigmatic progress, which results from the lack of unified understanding of the given concept, and reorganization complexity. According to the author, paradigmatic transformation in pedagogy and education mainly depends on the fundamental changes of the scientific worldview. Though, compared to the worldview alterations, paradigmatic changes take more time and effort. So, in order to overcome this lagging behind, a lot of contradicting views appear in the modern pedagogic theory. The research methodology is based on the works by T. Coon, defining the paradigm as the complex of theoretical and methodological notions, more general than the theory, concept and attitude. In author’s opinion, turning back to the scientific interpretation of the paradigm concept can overcome the existing misunderstanding of educational experience and its prospects, and ensure the adequate perception of pedagogic reality. 

  15. Dark matter and the neutrino portal paradigm

    CERN Document Server

    González-Macías, Vannia; Wudka, José

    2016-01-01

    A simple extension of the Standard Model (SM) that provides an explicit realization of the dark-matter (DM) neutrino-portal paradigm is presented. The leading interactions between the dark sector, containing scalars and relic fermions, and the SM involve neutrinos. This model meets all observational constraints.

  16. ACCOUNTING PARADIGMS WHICH FAVOR HISTORICAL COST

    Directory of Open Access Journals (Sweden)

    Valentin Gabriel CRISTEA

    2014-05-01

    Full Text Available Henning Kirkegaard shows that the evolution of accounting is to shift from one paradigm to another . Business continuity perspective should guide the company into the future , without confine it exclusively in the past. Accounting in its classical form , however, can not be dissociated from the historical cost evaluation .

  17. Toward an Ecological Paradigm in Adventure Programming

    Science.gov (United States)

    Beringer, Almut

    2004-01-01

    Many forms of adventure therapy, in particular wilderness therapy, rely on challenges in the outdoors to achieve objectives of client change. While nature is drawn on as a medium for therapy and healing, some adventure therapists give nature little if any mention when it comes to explaining therapeutic success. The dominant paradigm in psychology…

  18. Augmenting the ADDIE Paradigm for Instructional Design

    Science.gov (United States)

    Ni, Xiaopeng; Branch, Robert Maribe

    2008-01-01

    The authors discuss topics appropriate for augmenting the ADDIE paradigm for instructional design. The topics selected are based on data from a study of working professionals who successfully completed an instructional design and technology certificate program and who identified related topics that they regarded as beneficial. The participants…

  19. A Review of Process Modeling Language Paradigms

    Institute of Scientific and Technical Information of China (English)

    MA Qin-hai; GUAN Zhi-min; LI Ying; ZHAO Xi-nan

    2002-01-01

    Process representation or modeling plays an important role in business process engineering.Process modeling languages can be evaluated by the extent to which they provide constructs useful for representing and reasoning about the aspects of a process, and subsequently are chosen for a certain purpose.This paper reviews process modeling language paradigms and points out their advantages and disadvantages.

  20. Redesigning Higher Education: Embracing a New Paradigm

    Science.gov (United States)

    Watson, William R.; Watson, Sunnie Lee

    2014-01-01

    Higher education is under enormous pressure to transform itself and embrace a new paradigm. Operating under an outdated model that no longer aligns with the realities of modern society, institutions of higher education are recognizing the need to drastically remake themselves or possibly cease to exist. This article explores the current landscape…

  1. Paradigms and pragmatic constructivism: a reply

    DEFF Research Database (Denmark)

    Nørreklit, Hanne; Nørreklit, Lennart; Mitchell, Falconer

    2010-01-01

    to the analysis of the comment on their past paper. Findings - In addressing each of the issues in turn the authors clarify their analysis. Originality/value - The paper provides an argument for the development of a paradigm for accounting practice derived from the use of pragmatic constructivism....

  2. Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

    Science.gov (United States)

    Fellows, Christopher R.; Matta, Csaba; Zakany, Roza; Khan, Ilyas M.; Mobasheri, Ali

    2016-01-01

    Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue. PMID:28066501

  3. Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?

    Institute of Scientific and Technical Information of China (English)

    Ann; De; Becker; Ivan; Van; Riet

    2016-01-01

    Mesenchymal stromal cells(MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires the homing and migration of MSCs to a target tissue. Although MSC hominghas been described, this process does not appear to be highly efficacious because only a few cells reach the target tissue and remain there after systemic administration. This has been ascribed to low expression levels of homing molecules, the loss of expression of such molecules during expansion, and the heterogeneity of MSCs in cultures and MSC culture protocols. To overcome these limitations, different methods to improve the homing capacity of MSCs have been examined. Here, we review the current understanding of MSC homing, with a particular focus on homing to bone marrow. In addition, we summarize the strategies that have been developed to improve this process. A better understanding of MSC biology, MSC migration and homing mechanisms will allow us to prepare MSCs with optimal homing capacities. The efficacy of therapeutic applications is dependent on efficient delivery of the cells and can, therefore, only benefit from better insights into the homing mechanisms.

  4. Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda;

    2011-01-01

    Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic...... (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media....

  5. Collagen Promotes Higher Adhesion, Survival and Proliferation of Mesenchymal Stem Cells.

    Directory of Open Access Journals (Sweden)

    Chinnapaka Somaiah

    Full Text Available Mesenchymal stem cells (MSC can differentiate into several cell types and are desirable candidates for cell therapy and tissue engineering. However, due to poor cell survival, proliferation and differentiation in the patient, the therapy outcomes have not been satisfactory. Although several studies have been done to understand the conditions that promote proliferation, differentiation and migration of MSC in vitro and in vivo, still there is no clear understanding on the effect of non-cellular bio molecules. Of the many factors that influence the cell behavior, the immediate cell microenvironment plays a major role. In this context, we studied the effect of extracellular matrix (ECM proteins in controlling cell survival, proliferation, migration and directed MSC differentiation. We found that collagen promoted cell proliferation, cell survival under stress and promoted high cell adhesion to the cell culture surface. Increased osteogenic differentiation accompanied by high active RHOA (Ras homology gene family member A levels was exhibited by MSC cultured on collagen. In conclusion, our study shows that collagen will be a suitable matrix for large scale production of MSC with high survival rate and to obtain high osteogenic differentiation for therapy.

  6. Development of novel monoclonal antibodies that define differentiation stages of human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline; Kortesidis, Angela; Zannettino, Andrew C W;

    2011-01-01

    fewer differentiated alkaline phosphatase(+) cells compared to STRO-1(+/-)/Collagen VI(+) hMSC, suggesting that Collagen VI on the cell membrane exclusively defines differentiated MSCs. In conclusion, we have generated a panel of high quality antibodies to be used for characterization of MSCs...... of clonogenic hMSC from BMMNCs as single reagents. Using mass-spectrometric analysis, we identified the antigen recognised by DJ3 as CD44, whereas DJ9 and DJ18 recognized HLA-DRB1 and Collagen VI, respectively. The identified proteins were highly expressed throughout in vitro osteogenic- and adipogenic...... mice with hMSC, and by using a panel of subsequent screening methods. Flow cytometry analysis revealed that 83.5, 1.1, and 8.5% of primary cultures of hMSC were double positive for STRO-1 and either of DJ 3, 9, and 18, respectively. However, none of the three DJ antibodies allowed enrichment...

  7. Stem-cell treatment in disc degeneration: What is the evidence?

    Directory of Open Access Journals (Sweden)

    Manuela Peletti-Figueiró

    2013-01-01

    Full Text Available To review the potential role of stem cells in treating degenerative disc disease of the intervertebral disc (IVD. A review was performed of articles from the Medline database concerning stem cells and degenerative disc disease (DDD. To discuss the data, the papers were classified as: review, in vitro, experimental, and clinical. The currently available treatments were basically for symptom reduction, not to revert the IVD degenerative process. The use of mesenchymal stem cells (MSC is being proposed as an option of treatment for DDD. In vitro studies have shown that the MSC are able to differentiate into NP cells and that the MSC also reduce the inflammatory levels of the degenerated IVD. Besides, experimental studies demonstrated that the MSC remained viable when injected into the IVD, and that they were able to regenerate partially from the degenerated IVD and its structure. The few clinical studies found in the literature presented diverging results. The use of MSC is being widely studied and shows promising results for the treatment of DDD. Although many advances are being achieved in studies in vitro and experimental, there is a lack of clinical studies to prove the role of MSC in DDD management.

  8. Mesenchymal stem cells from different organs are characterized by distinct topographic Hox codes.

    Science.gov (United States)

    Ackema, Karin B; Charité, Jeroen

    2008-10-01

    Mesenchymal stem cells (MSC) are multipotent cells found as part of the stromal compartment of the bone marrow and in many other organs. They can be identified in vitro as CFU-F (colony forming unit-fibroblast) based on their ability to form adherent colonies of fibroblast-like cells in culture. MSC expanded in vitro retain characteristics appropriate to their tissue of origin. This is reflected in their propensity for differentiating towards specific lineages, and their capacity to generate, upon retransplantation in vivo, a stroma supporting typical lineages of hematopoietic cells. Hox genes encode master regulators of regional specification and organ development in the embryo and are widely expressed in the adult. We investigated whether they could be involved in determining tissue-specific properties of MSC. Hox gene expression profiles of individual CFU-F colonies derived from various organs and anatomical locations were generated, and the relatedness between these profiles was determined using hierarchical cluster analysis. This revealed that CFU-F have characteristic Hox expression signatures that are heterogeneous but highly specific for their anatomical origin. The topographic specificity of these Hox codes is maintained during differentiation, suggesting that they are an intrinsic property of MSC. Analysis of Hox codes of CFU-F from vertebral bone marrow suggests that MSC originate over a large part of the anterioposterior axis, but may not originate from prevertebral mesenchyme. These data are consistent with a role for Hox proteins in specifying cellular identity of MSC.

  9. Towards personalized regenerative cell therapy

    DEFF Research Database (Denmark)

    Lin, Lin; Bolund, Lars; Luo, Yonglun

    2015-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells with the capacity of self-renewal and multilineage differentiation, and can be isolated from several adult tissues. However, isolating MSCs from adult tissues for cell therapy is hampered by the invasive procedure, the rarity of the cells...... and their attenuated proliferation capacity when cultivated and expanded in vitro. Human MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have now evolved as a promising alternative cell source for MSCs and regenerative medicine. Several groups, including ours, have reported successful derivation...... of functional iPSC-MSCs and applied these cells in MSC-based therapeutic testing. Still, the current experience and understanding of iPSC-MSCs with respect to production methods, safety and efficacy are primitive. In this review, we highlight the methodological progress in iPSC-MSC research, describing...

  10. Stirred tank bioreactor culture combined with serum-/xenogeneic-free culture medium enables an efficient expansion of umbilical cord-derived mesenchymal stem/stromal cells.

    Science.gov (United States)

    Mizukami, Amanda; Fernandes-Platzgummer, Ana; Carmelo, Joana G; Swiech, Kamilla; Covas, Dimas T; Cabral, Joaquim M S; da Silva, Cláudia L

    2016-08-01

    Mesenchymal stem/stromal cells (MSC) are being widely explored as promising candidates for cell-based therapies. Among the different human MSC origins exploited, umbilical cord represents an attractive and readily available source of MSC that involves a non-invasive collection procedure. In order to achieve relevant cell numbers of human MSC for clinical applications, it is crucial to develop scalable culture systems that allow bioprocess control and monitoring, combined with the use of serum/xenogeneic (xeno)-free culture media. In the present study, we firstly established a spinner flask culture system combining gelatin-based Cultispher(®) S microcarriers and xeno-free culture medium for the expansion of umbilical cord matrix (UCM)-derived MSC. This system enabled the production of 2.4 (±1.1) x10(5) cells/mL (n = 4) after 5 days of culture, corresponding to a 5.3 (±1.6)-fold increase in cell number. The established protocol was then implemented in a stirred-tank bioreactor (800 mL working volume) (n = 3) yielding 115 million cells after 4 days. Upon expansion under stirred conditions, cells retained their differentiation ability and immunomodulatory potential. The development of a scalable microcarrier-based stirred culture system, using xeno-free culture medium that suits the intrinsic features of UCM-derived MSC represents an important step towards a GMP compliant large-scale production platform for these promising cell therapy candidates.

  11. Molecular characterisation of stromal populations derived from human embryonic stem cells

    DEFF Research Database (Denmark)

    Harkness, L.; Twine, N. A.; Abu Dawud, R.;

    2015-01-01

    Human bone marrow-derived stromal (skeletal) stem cells (BM-hMSC) are being employed in an increasing number of clinical trials for tissue regeneration. A limiting factor for their clinical use is the inability to obtain sufficient cell numbers. Human embryonic stem cells (hESC) can provide an un......ESC-stromal cells can thus be considered as a possible alternative candidate cells for hMSC, to be employed in regenerative medicine protocols.......Human bone marrow-derived stromal (skeletal) stem cells (BM-hMSC) are being employed in an increasing number of clinical trials for tissue regeneration. A limiting factor for their clinical use is the inability to obtain sufficient cell numbers. Human embryonic stem cells (hESC) can provide...... an unlimited source of clinical grade cells for therapy. We have generated MSC-like cells from hESC (called here hESC-stromal) that exhibit surface markers and differentiate to osteoblasts and adipocytes, similar to BM-hMSC. In the present study, we used microarray analysis to compare the molecular phenotype...

  12. Mesenchymal stem cells with high telomerase expression do not actively restore their chromosome arm specific telomere length pattern after exposure to ionizing radiation

    DEFF Research Database (Denmark)

    Graakjaer, Jesper; Christensen, Rikke; Kolvraa, Steen;

    2007-01-01

    BACKGROUND: Previous studies have demonstrated that telomeres in somatic cells are not randomly distributed at the end of the chromosomes. We hypothesize that these chromosome arm specific differences in telomere length (the telomere length pattern) may be actively maintained. In this study we...... investigate the existence and maintenance of the telomere length pattern in stem cells. For this aim we studied telomere length in primary human mesenchymal stem cells (hMSC) and their telomerase-immortalised counterpart (hMSC-telo1) during extended proliferation as well as after irradiation. Telomere lengths...... were measured using Fluorescence In Situ Hybridization (Q-FISH). RESULTS: A telomere length pattern was found to exist in primary hMSC's as well as in hMSC-telo1. This pattern is similar to what was previously found in lymphocytes and fibroblasts. The cells were then exposed to a high dose of ionizing...

  13. Defining human mesenchymal stem cell efficacy in vivo

    Directory of Open Access Journals (Sweden)

    Lennon Donald P

    2010-10-01

    Full Text Available Abstract Allogeneic human mesenchymal stem cells (hMSCs can suppress graft versus host disease (GvHD and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo. Models which may provide insight into hMSC bioactivity in vivo would provide a means to distinguish hMSCs for clinical utility. hMSC function has been described as both regenerative and trophic through the production of bioactive factors. The regenerative component involves the multi-potentiality of hMSC progenitor differentiation. The secreted factors generated by the hMSCs are milieu and injury specific providing unique niches for responses in vivo. These bioactive factors are anti-scarring, angiogenic, anti-apoptotic as well as regenerative. Further, from an immunological standpoint, hMSC's can avoid host immune response, providing xenographic applications. To study the in vivo immuno-regulatory effectiveness of hMSCs, we used the ovalbumin challenge model of acute asthma. This is a quick 3 week in vivo pulmonary inflammation model with readily accessible ways of measuring effectiveness of hMSCs. Our data show that there is a direct correlation between the traditional ceramic cube score to hMSCs attenuation of cellular recruitment due to ovalbumin challenge. The results from these studies verify the in vivo immuno-modulator effectiveness of hMSCs and support the potential use of the ovalbumin model as an in vivo model of hMSC potency and efficacy. Our data also support future directions toward exploring hMSCs as an alternative therapeutic for the treatment of airway inflammation associated with asthma.

  14. Modeling Electrophysiological Coupling and Fusion between Human Mesenchymal Stem Cells and Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Joshua Mayourian

    2016-07-01

    Full Text Available Human mesenchymal stem cell (hMSC delivery has demonstrated promise in preclinical and clinical trials for myocardial infarction therapy; however, broad acceptance is hindered by limited understanding of hMSC-human cardiomyocyte (hCM interactions. To better understand the electrophysiological consequences of direct heterocellular connections between hMSCs and hCMs, three original mathematical models were developed, representing an experimentally verified triad of hMSC families with distinct functional ion channel currents. The arrhythmogenic risk of such direct electrical interactions in the setting of healthy adult myocardium was predicted by coupling and fusing these hMSC models to the published ten Tusscher midcardial hCM model. Substantial variations in action potential waveform-such as decreased action potential duration (APD and plateau height-were found when hCMs were coupled to the two hMSC models expressing functional delayed rectifier-like human ether à-go-go K+ channel 1 (hEAG1; the effects were exacerbated for fused hMSC-hCM hybrid cells. The third family of hMSCs (Type C, absent of hEAG1 activity, led to smaller single-cell action potential alterations during coupling and fusion, translating to longer tissue-level mean action potential wavelength. In a simulated 2-D monolayer of cardiac tissue, re-entry vulnerability with low (5% hMSC insertion was approximately eight-fold lower with Type C hMSCs compared to hEAG1-functional hMSCs. A 20% decrease in APD dispersion by Type C hMSCs compared to hEAG1-active hMSCs supports the claim of reduced arrhythmogenic potential of this cell type with low hMSC insertion. However, at moderate (15% and high (25% hMSC insertion, the vulnerable window increased independent of hMSC type. In summary, this study provides novel electrophysiological models of hMSCs, predicts possible arrhythmogenic effects of hMSCs when directly coupled to healthy hCMs, and proposes that isolating a subset of hMSCs absent

  15. [Therapeutic potential of human mesenchymal stromal cells secreted components: a problem with standartization].

    Science.gov (United States)

    Sagaradze, G D; Grigorieva, O A; Efimenko, A Yu; Chaplenko, A A; Suslina, S N; Sysoeva, V Yu; Kalinina, N I; Akopyan, Zh A; Tkachuk, V A

    2015-01-01

    Regenerative medicine approaches, such as replacement of damaged tissue by ex vivo manufactured constructions or stimulation of endogenous reparative and regenerative processes to treat different diseases, are actively developing. One of the major tools for regenerative medicine are stem and progenitor cells, including multipotent mesenchymal stem/stromal cells (MSC). Because the paracrine action of bioactive factors secreted by MSC is considered as a main mechanism underlying MSC regenerative effects, application of MSC extracellular secreted products could be a promising approach to stimulate tissue regeneration; it also has some advantages compared to the injection of the cells themselves. However, because of the complexity of composition and multiplicity of mechanisms of action distinguished the medicinal products based on bioactive factors secreted by human MSC from the most of pharmaceuticals, it is important to develop the approaches to their standardization and quality control. In the current study, based on the literature data and guidelines as well as on our own experimental results, we provided rationalization for nomenclature and methods of quality control for the complex of extracellular products secreted by human adipose-derived MSC on key indicators, such as "Identification", "Specific activity" and "Biological safety". Developed approaches were tested on the samples of conditioned media contained products secreted by MSC isolated from subcutaneous adipose tissue of 30 donors. This strategy for the standardization of innovative medicinal products and biomaterials based on the bioactive extracellular factors secreted by human MSC could be applicable for a wide range of bioactive complex products, produced using the different types of stem and progenitor cells.

  16. Code Component Composition Reuse Is a New Programming Paradigm

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    After describing the characteristics of programming paradigm,this pap er introduces the approach of code component composition reuse in detail, propos es and discusses viewpoint that code component composition reuse is a kind of ne w programming paradigm. This paper also specifies the characteristics of this ne w programming paradigm in detail, and points out some issues that must be resolv ed for using this new programming paradigm.

  17. Changing the Dominant Paradigm in Economics

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Mollo

    2015-10-01

    Full Text Available This article addresses the discussion proposed by the World Academy of Art & Science (WAAS about the need to build a new paradigm to confront the challenges of the global society and to move across to a New Society discussing specific problems related to economic globalization and proposing changes. The ways in which economic orthodoxy and heterodoxy analyze the role of the State and the question of sustainability of development and the problems of environmental sustainability depend on their different views or theoretical arguments about the role of the market. The article contrasts the mainstream economics arguments to support the free market context of globalization with Post-Keynesian and Marxist’s skeptical or critical views. Finally, it proposes some strategies to face the critical aspects analyzed making suggestions to move to another dominant economic paradigm.

  18. [Assistance to the climacteric woman: new paradigms].

    Science.gov (United States)

    Lorenzi, Dino Roberto Soares De; Catan, Lenita Binelli; Moreira, Karen; Artico, Graziela Rech

    2009-01-01

    Population aging is a demographic reality for Brazil. Consequently, in the next years it is expected a progressive increase in seeking health care services in the country by women with complaints related to climacterium. Parallel to it, assistance at this part of woman's life has been going through a paradigm shift which has imposed to health professionals a change of attitude in relation to this stage of woman's life. Today it is acknowledged that the climacterium is influenced by biological, psychosocial and cultural factors, whose knowledge is fundamental for planning a more qualified and humanized care. This article proposes a reflection on the paradigm shifts in assistance at climacterium, highlighting important aspects as multidisciplinarity and interdisciplinarity, so as to serve better this portion of population, and provide it with more integrated and individualized care, bringing together knowledge and sensitivity, and always aiming at a better quality of life.

  19. Reviving Campbell's paradigm for attitude research.

    Science.gov (United States)

    Kaiser, Florian G; Byrka, Katarzyna; Hartig, Terry

    2010-11-01

    Because people often say one thing and do another, social psychologists have abandoned the idea of a simple or axiomatic connection between attitude and behavior. Nearly 50 years ago, howev