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Sample records for birgitta wallstedt msc

  1. Birgitta festival tulekul

    Index Scriptorium Estoniae

    2006-01-01

    Birgitta festivali üritustest Tallinnas Pirita kloostri varemetes: 11. ja 12. aug. Astor Piazzolla tango-ooper "Maria de BuenosAires", 15. aug. Mozarti ooper "Tituse halastus", 17. aug. D. Shostakovitshi ooper "Mtsenski maakonna lady Macbeth", 18. aug. Carl Orffi "Carmina Burana, 19. aug. Verdi "Reekviem", 20. aug. Tõnis Mägi, Ultima Thule ja Tallinna Kammerorkestri kontsert

  2. Birgitta festivali kava teada

    Index Scriptorium Estoniae

    2008-01-01

    Augustis Tallinnas toimuva Birgitta festivali kavas ka humoristlik etendus "Kino ja komöödia" (viiuldaja Gidon Kremeri elust muusiku enda osavõtul), Don Juani teema käsitlus Hispaania flamenkoteatri esituses, G. Donizetti ooper "Maria Stuart" (Moskva Novaja Opera) ja B. Britteni ooper "Kruvipööre"

  3. Birgitta festivali elav tuli

    Index Scriptorium Estoniae

    2007-01-01

    Birgitta festivalil Pirita kloostri müüride vahel 10.-19. aug. mängukavas: Moskva ooperiteatri Novaya Opera trupp esitamas ooperit, Maria Callase gala, klassikalist ja dzhässballetti, Vene Keiserlik Ballett kava "Tshaikovski in Swing", Anton Rubinshteini ooper "Deemon" (lavastaja Mihhail Jefremov), Arthur Honeggeri oratoorium "Jeanne d'Arc tuleriidal" (lavastaja Üllar Saaremäe, peaosas Mirtel Pohla)

  4. Birgitta festival valge tiiva all / Toomas Velmet

    Index Scriptorium Estoniae

    Velmet, Toomas, 1942-

    2007-01-01

    19. augustil Pirita kloostris Birgitta festivali raames toimunud kontserdist "Tchaikovsky.Ballet@Classics.Jazz", kus osalesid Novaja Opera orkester, Imperial Ballet, Estonian Dream Big Band ja eesti jazztantsijad

  5. Birgitta festival / Heili Vaus-Tamm

    Index Scriptorium Estoniae

    Vaus-Tamm, Heili, 1961-

    2007-01-01

    Birgitta festivalil Pirita kloostris 10. - 19. augustini toimuvast lühidalt: Arthur Honeggeri oratoorium "Jeanne d'Arc tuleriidal", Astor Piazolla tango-ooper "Maria de Buenos Aires", Carl Orffi "Carmina Burana" jpt.

  6. Power and Authority. Birgitta of Sweden and her Revelations

    OpenAIRE

    Salmesvuori, Päivi

    2009-01-01

    In the High Middle Ages female saints were customarily noble virgins. Thus, as a wife and a mother of eight children, the Swedish noble lady Birgitta (1302/3 1373) was an atypical candidate for sanctity. However, in 1391 she was canonized only 18 years after her death and became a role model for many late medieval women, who were mothers and widows. The dissertation Power and Authority Birgitta of Sweden and Her Revelations investigates how Birgitta went about establishing her power an...

  7. Ülestähendusi Birgitta festivalilt 2009 / Raili Sule

    Index Scriptorium Estoniae

    Sule, Raili, 1944-

    2009-01-01

    13.-23. augustini Pirita kloostri varemetes toimunud Tallinna Filharmoonia korraldatud Birgitta festivali raames toimunud Dmitri Bertmanni lavastustest - Umberto Giordano "Siber" ja Giuseppe Verdi "Falstaff"

  8. Birgitta festival on mõtlevale ja tundvale inimesele / Heili Vaus-Tamm

    Index Scriptorium Estoniae

    Vaus-Tamm, Heili, 1961-

    2010-01-01

    Birgitta festival (12.–21. augustini) on kuue tegutsemisaasta jooksul kujundanud välja oma põhimõtted ja suunad. Festival pakub publikule põnevaid psühholoogilisi lavastusi maailma teatrikunsti tasemel, ning seda arusaadavas ja esteetilises vormis

  9. Teater Pan-Optikum tõstab Birgitta festivali lendu / Sigrun Fritsch ; intervjueerinud Heili Vaus-Tamm

    Index Scriptorium Estoniae

    Fritsch, Sigrun

    2010-01-01

    12.-21. augustini Pirita kloostris toimuval Birgitta festivalil etendub Glucki ooper "Orpheus ja Eurydike", lavastaja Georg Rootering. Teater Pan.Optikum ("füüsiline teater" ehk Aktionstheater) osaleb lavastuses videoprojektsiooni ja lauljate karakterite dubleerimisega

  10. Oo, püha Birgitta, mis toimub augustis sinu kloostri vanade varemete vahel?

    Index Scriptorium Estoniae

    2007-01-01

    Birgitta festivalil Pirita kloostri varemetes mängukavas: Arthur Honeggeri oratoorium "Jeanne d'Arc tuleriidal" (10. ja 11. aug., lavastajaks Üllar Saaremäe, peaosas Mirtel Pohla ja Benedictuse osatäitjaks Rain Simmul), Piazolla tango-ooper "Maria de Buenos Aires" (14. aug.), Carl Orffi lavaline kantaat "Carmina Burana" (15. aug.), A. Rubinshteini ooper "Deemon" (16. aug.), lavastatud galakontsert filmikatketega ooperidiiva Maria Callasest (17. aug.), klassikalise ja dzhässballeti õhtud Vene Keiserlikult balletitrupilt (18. ja 19. aug.)

  11. Stridskvinnan Birgitta

    OpenAIRE

    Searby, Denis

    2017-01-01

    “Stridskvinnan Birgitta” focuses on aspects of Birgitta’s writings less palatable to moderntastes, such as images of violent punishment in hell and purgatory. It brings in the exampleof the American Catholic author Flannery O’Connor to illustrate how, from Birgitta’sperspective, violent images could represent an occasion of grace for the recipient of herrevelations. It also discusses Birgitta’s support for the king’s “crusade” to the Baltic countriesfor the purposes of Christianizing them and...

  12. MSC in clinics: Liver Transplantation

    OpenAIRE

    DETRY, Olivier

    2014-01-01

    For several years, mesenchymal stem cells (MSC) have been evaluated in vivo and in vitro for their immunomodulatory, anti-inflammatory, anti- ischemia-reperfusion injury and “tissue repair” properties. These characteristics could make them interesting in various clinical applications, and particularly in organ transplantation. Taking advantage of our centre expertise and experience concerning MSC use in graft-versus-host disease after bone marrow transplantation and using already functioning ...

  13. Hungarian medical physics MSc education

    International Nuclear Information System (INIS)

    Legrady, D.; Czifrus, Z.; Zarand, P.; Aszodi, A.; Pesznyak, C.; Major, T.

    2012-01-01

    The medical physics specialisation aims at providing high level interdisciplinary theoretical and practical knowledge and readily applicable skills, which can put into action in both the clinical and the R and D field. The first competence based gradual medical physics course in the B.Sc./M.Sc. system in Hungary was launched two years ago at the Faculty of Natural Sciences of Budapest University of Technology and Economics managed by the Institute of Nuclear Techniques. The MSc programme was compiled on the base of EFOMP, IPEM, AAPM and IAEA recommendations. The course curriculum comprises fundamental physical subjects (atomic and molecular physics, nuclear physics and particle physics) as well as fundamental medical knowledge (anatomy, physiology and radiobiology) required for subjects of diagnostic and therapy. Students of this MSc branch may chose further subjects from a 'compulsory optional' set of subjects, which contains medical imaging, X-ray diagnostics, radiation therapy, magnetic resonance imaging, radiation protection, Monte Carlo calculation and its clinical applications, ultrasound diagnostics and nuclear medicine. (authors)

  14. Cellular Kinetics of Perivascular MSC Precursors

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. Sertifikaatit ravintolassa : Luomu, UTZ, MSC, ASC

    OpenAIRE

    Hakamäki, Henna

    2017-01-01

    Tämän opinnäytetyön tarkoituksena on selvittää tietävätkö ihmiset, mitä sertifikaatit tarkoittavat, olisivatko asiakkaat valmiita maksamaan sertifioiduista raaka-aineista tehdystä ruoasta enemmän ja markkinoivatko ravintolat käytössä olevia sertifikaatteja riittävästi saadakseen siitä hyödyn. Tulosten perusteella pyrittiin selvittämään kannattaako yritysten panostaa sertifikaattien markkinointiin. Teoriaosassa käsitellään neljää opinnäytetyöhön valikoitua sertifikaattia: luomu, UTZ, MSC ...

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

    Directory of Open Access Journals (Sweden)

    Ruth S Waterman

    Full Text Available 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.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.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.

  18. TACT: A Set of MSC/PATRAN- and MSC/NASTRAN- based Modal Correlation Tools

    Science.gov (United States)

    Marlowe, Jill M.; Dixon, Genevieve D.

    1998-01-01

    This paper describes the functionality and demonstrates the utility of the Test Analysis Correlation Tools (TACT), a suite of MSC/PATRAN Command Language (PCL) tools which automate the process of correlating finite element models to modal survey test data. The initial release of TACT provides a basic yet complete set of tools for performing correlation totally inside the PATRAN/NASTRAN environment. Features include a step-by-step menu structure, pre-test accelerometer set evaluation and selection, analysis and test result export/import in Universal File Format, calculation of frequency percent difference and cross-orthogonality correlation results using NASTRAN, creation and manipulation of mode pairs, and five different ways of viewing synchronized animations of analysis and test modal results. For the PATRAN-based analyst, TACT eliminates the repetitive, time-consuming and error-prone steps associated with transferring finite element data to a third-party modal correlation package, which allows the analyst to spend more time on the more challenging task of model updating. The usefulness of this software is presented using a case history, the correlation for a NASA Langley Research Center (LaRC) low aspect ratio research wind tunnel model. To demonstrate the improvements that TACT offers the MSC/PATRAN- and MSC/DIASTRAN- based structural analysis community, a comparison of the modal correlation process using TACT within PATRAN versus external third-party modal correlation packages is presented.

  19. 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...... other than DTUs and allow qualified students to enter the MSc programmes. The focus of the present work is a comparison of how international and Danish students perform within specific modules of the MSc curriculum in Engineering Design and Applied Mechanics at Technical University of Denmark...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. 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.

  2. MSc Agriculture students working with ex-campus stakeholders

    DEFF Research Database (Denmark)

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

    2014-01-01

    both on BSc and MSc level. For many students this results in concerns whether their knowledge, skills and competencies are sufficient when confronted with reality in a job, i.e. in a lack of professional confidence. Therefore when revising the program we focused on competences in contextualizing...

  3. 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....

  4. 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....

  5. 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....

  6. 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....

  7. 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.

  8. Using PAFEC as a preprocessor for MSC/NASTRAN

    International Nuclear Information System (INIS)

    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

  9. Using PAFEC as a preprocessor for MSC/NASTRAN

    International Nuclear Information System (INIS)

    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

  10. Review of Signaling Pathways Governing MSC Osteogenic and Adipogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Aaron W. James

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSC are multipotent cells, functioning as precursors to a variety of cell types including adipocytes, osteoblasts, and chondrocytes. Between osteogenic and adipogenic lineage commitment and differentiation, a theoretical inverse relationship exists, such that differentiation towards an osteoblast phenotype occurs at the expense of an adipocytic phenotype. This balance is regulated by numerous, intersecting signaling pathways that converge on the regulation of two main transcription factors: peroxisome proliferator-activated receptor-γ (PPARγ and Runt-related transcription factor 2 (Runx2. These two transcription factors, PPARγ and Runx2, are generally regarded as the master regulators of adipogenesis and osteogenesis. This review will summarize signaling pathways that govern MSC fate towards osteogenic or adipocytic differentiation. A number of signaling pathways follow the inverse balance between osteogenic and adipogenic differentiation and are generally proosteogenic/antiadipogenic stimuli. These include β-catenin dependent Wnt signaling, Hedgehog signaling, and NELL-1 signaling. However, other signaling pathways exhibit more context-dependent effects on adipogenic and osteogenic differentiation. These include bone morphogenic protein (BMP signaling and insulin growth factor (IGF signaling, which display both proosteogenic and proadipogenic effects. In summary, understanding those factors that govern osteogenic versus adipogenic MSC differentiation has significant implications in diverse areas of human health, from obesity to osteoporosis to regenerative medicine.

  11. A new antibiotic with potent activity targets MscL.

    Science.gov (United States)

    Iscla, Irene; Wray, Robin; Blount, Paul; Larkins-Ford, Jonah; Conery, Annie L; Ausubel, Frederick M; Ramu, Soumya; Kavanagh, Angela; Huang, Johnny X; Blaskovich, Mark A; Cooper, Matthew A; Obregon-Henao, Andres; Orme, Ian; Tjandra, Edwin S; Stroeher, Uwe H; Brown, Melissa H; Macardle, Cindy; van Holst, Nick; Ling Tong, Chee; Slattery, Ashley D; Gibson, Christopher T; Raston, Colin L; Boulos, Ramiz A

    2015-07-01

    The growing problem of antibiotic-resistant bacteria is a major threat to human health. Paradoxically, new antibiotic discovery is declining, with most of the recently approved antibiotics corresponding to new uses for old antibiotics or structurally similar derivatives of known antibiotics. We used an in silico approach to design a new class of nontoxic antimicrobials for the bacteria-specific mechanosensitive ion channel of large conductance, MscL. One antimicrobial of this class, compound 10, is effective against methicillin-resistant Staphylococcus aureus with no cytotoxicity in human cell lines at the therapeutic concentrations. As predicted from in silico modeling, we show that the mechanism of action of compound 10 is at least partly dependent on interactions with MscL. Moreover we show that compound 10 cured a methicillin-resistant S. aureus infection in the model nematode Caenorhabditis elegans. Our work shows that compound 10, and other drugs that target MscL, are potentially important therapeutics against antibiotic-resistant bacterial infections.

  12. Gamma irradiation and heat treatment for sterilization of Mushroom Spent Compost (MSC)

    International Nuclear Information System (INIS)

    Rosnani Abdul Rashid; Hassan Hamdani Mutaat; Foziah Ali; Zainab Harun; Hoe, P.C.K.; Mohd Meswan Maskom; Khairuddin Abdul Rahim

    2016-01-01

    Mushroom spent compost (MSC) refers to substrate residue from mushroom cultivation. MSC can be used as a material to improve soil properties for farming. MSC is also suitable as a carrier or substrate to hold beneficial microorganisms in bio fertilizer products. The carrier for bio fertilizer products must be sterilized completely before inoculating with bacteria inoculum. In this study, the effects of gamma irradiation and heat on sterilization of MSC were evaluated by microbial enumeration technique. The MSC was packed into polyethylene bags. The packed MSC were irradiated at different doses of 0 (control), 10, 20, 30, 40, 50 kGy, and heat sterilized at different autoclaving time of 0 (control), 15, 30, 45 and 60 minutes, separately. The irradiated and autoclaved samples were enumerated for viable colonies. The results showed that MSC was completely sterilized by gamma irradiation at the dose of 30 kGy whilst sterilization by heat required 30 minute autoclaving time. (author)

  13. Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease

    OpenAIRE

    de Witte, Samantha F. H.; Merino, Ana M.; Franquesa, Marcella; Strini, Tanja; van Zoggel, Johanna A. A.; Korevaar, Sander S.; Luk, Franka; Gargesha, Madhu; O?Flynn, Lisa; Roy, Debashish; Elliman, Steve J.; Newsome, Philip N.; Baan, Carla C.; Hoogduijn, Martin J.

    2017-01-01

    Background Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC. Methods MSC derived from human umbilical cords (ucMSC) were treated for 3?days in vitro with various inflammator...

  14. Transcriptome Analyses of Mosaic (MSC Mitochondrial Mutants of Cucumber in a Highly Inbred Nuclear Background

    Directory of Open Access Journals (Sweden)

    Tomasz L. Mróz

    2018-03-01

    Full Text Available Cucumber (Cucumis sativus L. has a large, paternally transmitted mitochondrial genome. Cucumber plants regenerated from cell cultures occasionally show paternally transmitted mosaic (MSC phenotypes, characterized by slower growth, chlorotic patterns on the leaves and fruit, lower fertility, and rearrangements in their mitochondrial DNAs (mtDNAs. MSC lines 3, 12, and 16 originated from different cell cultures all established using the highly inbred, wild-type line B. These MSC lines possess different rearrangements and under-represented regions in their mtDNAs. We completed RNA-seq on normalized and non-normalized cDNA libraries from MSC3, MSC12, and MSC16 to study their nuclear gene-expression profiles relative to inbred B. Results from both libraries indicated that gene expression in MSC12 and MSC16 were more similar to each other than MSC3. Forty-one differentially expressed genes (DEGs were upregulated and one downregulated in the MSC lines relative to B. Gene functional classifications revealed that more than half of these DEGs are associated with stress-response pathways. Consistent with this observation, we detected elevated levels of hydrogen peroxide throughout leaf tissue in all MSC lines compared to wild-type line B. These results demonstrate that independently produced MSC lines with different mitochondrial polymorphisms show unique and shared nuclear responses. This study revealed genes associated with stress response that could become selection targets to develop cucumber cultivars with increased stress tolerance, and further support of cucumber as a model plant to study nuclear-mitochondrial interactions.

  15. 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

  16. Seismic analysis of plutonium glovebox by MSC/NASTRAN

    International Nuclear Information System (INIS)

    Hirata, Masaru; Ishikawa, Kazuya; Korosawa, Makoto; Fukushima, Susumu; Hoshina, Hirofumi.

    1993-01-01

    Seismic analysis of the structural strength of gloveboxes is important for plutonium confinement evaluation. However, the analytical methods must be developed for evaluating the mutual displacement between the window frame and acrylic resin window panel with regard to plutonium confinement during an earthquake. Therefore, seismic analysis for a standard glovebox in Plutonium Fuel Research Facility at Oarai Research Establishment of JAERI has been conducted by FEM (Finite Element Method) computer code MSC/NASTRAN (MacNeal-Schwendler Corporation NASA Structural Analysis). Modelling of glovebox window frame has been investigated from the results of natural frequency analysis and static analysis. After the acquisition of a suitable model, displacement around the window frame and glovebox structural strength have been evaluated in detail by use of floor response spectrum analysis and time-history (transient response) analysis. (author)

  17. 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....

  18. Innovative taught MSc in Medical Visualisation and Human Anatomy.

    Science.gov (United States)

    Clunie, Lauren; Livingstone, Daniel; Rea, Paul M

    2015-06-01

    A relatively new, fully accredited MSc in Medical Visualisation and Human Anatomy, is now offered through a joint collaboration with the Laboratory of Human Anatomy, University of Glasgow and the Digital Design Studio, Glasgow School of Art. This degree combines training in digital technologies and intensive human anatomy training as a result of a long-standing successful partnership between these two esteemed institutes. The student also has to complete a research dissertation which encompasses both the digital perspective and a related medical, dental, surgical, veterinary (comparative anatomy) or life science specialty to enhance development in the digital field for a variety of specialties. This article discusses the background in development of this degree, the course structure and the career prospects and destinations for graduates of this unique degree programme.

  19. Pulling MscL open via N-terminal and TM1 helices: A computational study towards engineering an MscL nanovalve.

    Directory of Open Access Journals (Sweden)

    Adam D Martinac

    Full Text Available There are great opportunities in the manipulation of bacterial mechanosensitive (MS ion channels for specific and targeted drug delivery purposes. Recent research has shown that these ion channels have the potential to be converted into nanovalves through clever use of magnetic nanoparticles and magnetic fields. Using a combination of molecular dynamics (MD simulations and the finite element (FE modelling, this study investigates the theoretical feasibility of opening the MscL channel (MS channel of large conductance of E. coli by applying mechanical force directly to its N-terminus. This region has already been reported to function as a major mechanosensor in this channel. The stress-strain behaviour of each MscL helix was obtained using all atom MD simulations. Using the same method, we simulated two models, the wild-type (WT MscL and the G22N mutant MscL, both embedded in a POPE lipid bilayer. In addition to indicating the main interacting residues at the hydrophobic pore, their pairwise interaction energies were monitored during the channel gating. We implemented these inputs into our FE model of MscL using curve-fitting codes and continuum mechanics equations. In the FE model, the channel could be fully opened via pulling directly on the N-terminus and bottom of TM1 by mutating dominant van der Waals interactions in the channel pore; otherwise the stress generated on the channel protein can irreversibly unravel the N-secondary structure. This is a significant finding suggesting that applying force in this manner is sufficient to open an MscL nanovalve delivering various drugs used, for example, in cancer chemotherapy. More importantly, the FE model indicates that to fully operate an MscL nanovalve by pulling directly on the N-terminus and bottom of TM1, gain-of-function (GOF mutants (e.g., G22N MscL would have to be employed rather than the WT MscL channel.

  20. Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease

    NARCIS (Netherlands)

    S.F. De Witte (Samantha Fh); A. Merino (Ana); M. Franquesa (Marcella); T. Strini (Tanja); J.A.A. van Zoggel (Hanneke); S.S. Korevaar (Sander); F. Luk (Franka); M. Gargesha (Madhusudhana); O'Flynn, L. (Lisa); D. Roy (Debashish); Elliman, S.J. (Steve J.); Newsome, P.N. (Philip N.); C.C. Baan (Carla); M.J. Hoogduijn (Martin)

    2017-01-01

    textabstractBackground: Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC

  1. Influences Factors of the Cadmium Removal by Magnetic Solid Chelator Powder(MSC in Soil

    Directory of Open Access Journals (Sweden)

    LIU Jun-long

    2017-12-01

    Full Text Available Pot experiments were conducted for the purpose of analyzing the influencing effects for the magnetic solid chelator powder(MSC, magnetic solid chelator powder on removal of cadmium pollution in the soil. The influencing factors included straws,air drying,activation structural material, stirring time and repetition times, etc. The results showed that the straw addition in the soil decreased the removal efficiency of Cd. The different air drying degree in the soil also had the effect of MSC. The air drying in the soil affected the results more by comparison with the straws. When stirring time was 40 min, the removal rate of Cd was 22.67% and achieved the best removal efficiency. With the increasing of stirring time, the effect of MSC on Cd removal increased first, then decreased. Drying MSC material lost the effect of Cd removal in the soil. After activation(soaking in water for 12 h, MSC material could remov Cd in the soil once again. MSC material had removal and remediation effects on soil Cd, the removal effects depended on soil properties, material properties and operation process and other factors. The research of MSC materials in soil remediation had important practical significance.

  2. CASK/MSC/WP PREPARATION SYSTEM DESCRIPTION DOCUMENT

    International Nuclear Information System (INIS)

    S. Drummond

    2005-01-01

    The purpose of this system description document (SDD) is to establish requirements that drive the design of the Cask/MSC/WP preparation system and their bases to allow the design effort to proceed to license application. This SDD is a living document that will be revised at strategic points as the design matures over time. This SDD identifies the requirements and describes the system design, as they exist at this time, with emphasis on those attributes of the design provided to meet the requirements. This SDD has been developed to be an engineering tool for design control. Accordingly, the primary audience and users are design engineers. This type of SDD both leads and trails the design process. It leads the design process with regard to the flow down of upper tier requirements onto the system. Knowledge of these requirements is essential in performing the design process. This SDD trails the design with regard to the description of the system. The description provided in the SDD is a reflection of the results of the design process to date. This SDD addresses the ''Project Requirements Document'' (PRD) (Canori and Leitner 2003 [DIRS 166275]) requirements. Additional PRD requirements may be cited, as applicable, to drive the design of specific aspects of the system, with justifications provided in the basis. Functional and operational requirements applicable to this system are obtained from the ''Project Functional and Operational Requirements'' (F and OR) (Curry 2004 [DIRS 170557]) document. Other requirements to support the design process have been taken from higher-level requirements documents such as the ''Project Design Criteria Document'' (PDC) (BSC 2004 [DIRS 171599]) and the preclosure safety analyses

  3. CASK/MSC/WP PREPARATION SYSTEM DESCRIPTION DOCUMENT

    Energy Technology Data Exchange (ETDEWEB)

    S. Drummond

    2005-04-12

    The purpose of this system description document (SDD) is to establish requirements that drive the design of the Cask/MSC/WP preparation system and their bases to allow the design effort to proceed to license application. This SDD is a living document that will be revised at strategic points as the design matures over time. This SDD identifies the requirements and describes the system design, as they exist at this time, with emphasis on those attributes of the design provided to meet the requirements. This SDD has been developed to be an engineering tool for design control. Accordingly, the primary audience and users are design engineers. This type of SDD both leads and trails the design process. It leads the design process with regard to the flow down of upper tier requirements onto the system. Knowledge of these requirements is essential in performing the design process. This SDD trails the design with regard to the description of the system. The description provided in the SDD is a reflection of the results of the design process to date. This SDD addresses the ''Project Requirements Document'' (PRD) (Canori and Leitner 2003 [DIRS 166275]) requirements. Additional PRD requirements may be cited, as applicable, to drive the design of specific aspects of the system, with justifications provided in the basis. Functional and operational requirements applicable to this system are obtained from the ''Project Functional and Operational Requirements'' (F&OR) (Curry 2004 [DIRS 170557]) document. Other requirements to support the design process have been taken from higher-level requirements documents such as the ''Project Design Criteria Document'' (PDC) (BSC 2004 [DIRS 171599]) and the preclosure safety analyses.

  4. 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.

  5. USING OF MSC WITH DIFFERENT ONTOGENETIC MATURITY FOR CORRECTION OF CHRONIC FIBROSING LIVER DAMAGE

    Directory of Open Access Journals (Sweden)

    M. Y. Shagidulin

    2013-01-01

    Full Text Available Aim. To compare the effectiveness of MSC with different degree of ontogenetic maturity (MSC bone marrow – MSC BM and MSC umbilical cord – MSC UC on regenerative processes in injured liver. Methods. In 4 groups of experiments on Wistar rats (n = 80 with a model of fibrotic toxic liver damage (FLD it was studied the effect of MSCs with different degree of ontogenetic maturity on recovery processes at the regeneration of damaged liver: 1 gr. – Control, 2 gr. and 3 gr. introduction of MSC BM, included in Sphero®GEL-long in doses of 2.5 ×106 and 5.0 x 106 cells, respectively, and 4 gr. – introduction of MSC UC in the form of cell-spheroids (8–10 × 105 cells. The cells were injected into the damaged liver in 7 days after the end of FDL-modeling. The effect of cell therapy was studied during 180 days. The effectiveness of corrective therapy was evaluated by the results of functional and morphological investigations of livers (histological control of parenchymal and nonparenchy- mal liver tissue. Results. MSC BM in both doses and MSC UC contributed to a more rapid normalization of liver enzyme indices compared with the control (1 gr., but the differences in the rate of recovery of disturbed enzymatic liver functions between groups 2, 3 and 4 – were absent. In 90 days after the cell application it was determined a more pronounced recovery activity of cells in groups 3 and 4; in 180 days the more pronounced activation of recovery processes was observed in group 3; but in group 4 the sclerotic processes were more pro- nounced in this period. Conclusion. For the induction of recovery processes in damage liver it is advisable not to use the MSC UC, but to use MSC BM in the Sphero®GEL, because MSC BM exert not only local but also systemic immune-regulatory effect, increasing the pool of T-reg. cells, which are additional carriers of regenera- tion information in organism. 

  6. Comparison Virtual Landing Gear Drop Test for Commuter Aircraft Utilize MSC ADAMS And Solidworks Motion Analysis

    Science.gov (United States)

    Hidayat, Dony; Istiyanto, Jos; Agus Sumarsono, Danardono

    2018-04-01

    Loads at main landing gear while touchdown impact is function of aircraft weight and ground reaction load factor. In regulation states ground reaction load factor at Vsink = 3.05 m/s is below 3. Contact/impact force from simulation using MSC ADAMS is 94680 N, while using Solidworks Motion Analysis is 97691 N. The difference between MSC ADAMS and Solidworks Motion Analysis is 3.08%. The ground reaction load factor in MSC ADAMS is 2.78 while in Solidworks Motion Analysis is 2.87.

  7. Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease.

    Science.gov (United States)

    de Witte, Samantha F H; Merino, Ana M; Franquesa, Marcella; Strini, Tanja; van Zoggel, Johanna A A; Korevaar, Sander S; Luk, Franka; Gargesha, Madhu; O'Flynn, Lisa; Roy, Debashish; Elliman, Steve J; Newsome, Philip N; Baan, Carla C; Hoogduijn, Martin J

    2017-06-08

    Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC. MSC derived from human umbilical cords (ucMSC) were treated for 3 days in vitro with various inflammatory factors, interleukins, vitamins and serum deprivation. Their immunogenicity and immunomodulatory capacity were examined by gene-expression analysis, surface-marker expressions, IDO activity, PGE 2 secretion and inhibition of T cell proliferation and IFNγ production. Furthermore, their activation of NK cell cytotoxicity was investigated via CD107a expression on NK cells. The immunomodulatory capacity, biodistribution and survival of pre-treated ucMSC were investigated in a CCl 4 -induced liver disease mouse model. In addition, capacity of pre-treated MSC to ameliorate liver inflammation was examined in an ex vivo liver inflammation co-culture model. IFN-γ and a multiple cytokine cocktail (MC) consisting of IFN-γ, TGFβ and retinoic acid upregulated the expression of immunomodulatory factor PD-L1 and IDO activity. Subsequently, both treatments enhanced the capacity of ucMSC to inhibit CD4 and CD8 T cell proliferation and IFN-γ production. The susceptibility of ucMSC for NK cell lysis was decreased by IFN-β, TGFβ and MC treatment. In vivo, no immunomodulation was observed by the ucMSC. Four hours after intravenous infusion in mice with CCl 4 -induced inflammatory liver injury, the majority of ucMSC were trapped in the lungs. Rapid clearance of ucMSC(VitB 6 ), ucMSC(Starv + VitB 6 ) and ucMSC(MC) and altered bio-distribution of ucMSC(TGFβ) compared to untreated ucMSC was observed. In the ex vivo co-culture system with inflammatory liver slices ucMSC(MC) showed significantly enhanced

  8. Dihydrotestosterone induces pro-angiogenic factors and assists homing of MSC into the cardiac tissue.

    Science.gov (United States)

    Popa, Mirel-Adrian; Mihai, Maria-Cristina; Constantin, Alina; Şuică, Viorel; Ţucureanu, Cătălin; Costache, Raluca; Antohe, Felicia; Dubey, Raghvendra K; Simionescu, Maya

    2018-01-01

    The use of mesenchymal stem cells (MSC) as a therapeutic tool in cardiovascular diseases is promising. Since androgens exert some beneficial actions on the cardiovascular system, we tested our hypothesis that this hormone could promote MSC-mediated repair processes, also. Cultured MSCs isolated from Wharton's jelly were exposed to 30 nM dihydrotestosterone (DHT) for 1 or 4 days and the effects of the hormone on their growth/migration/adhesion and the underlying mechanisms were assessed. Results were obtained by real-time cell impedance measurements, and DNA quantification showed that DHT increased MSC proliferation by ~30%. As determined by xCELLigence system, DHT augmented (~2 folds) the migration of MSC toward cardiac tissue slices (at 12 h), and this effect was blocked by flutamide, an androgen receptor (AR) antagonist. Exposure of cells to DHT, upregulated the gene and protein expression of AR , EMMPRIN and MMP-9 and downregulated the expression of MMP-2 DHT significantly induced the release of nitric oxide by MSC (≥2-fold) and flutamide blocked this effect. When MSCs were co-cultured with cardiac slices, immunohistochemical analysis and qRT-PCR showed that the integration of DHT-stimulated MSC was significantly higher than that of in controls. In conclusion, our findings provide the first evidence that DHT promotes MSC growth, migration and integration into the cardiac slices. The modulating effects of DHT were associated with upregulation of ARs and of key molecules known to promote tissue remodeling and angiogenesis. Our findings suggest that priming of MSC with DHT may potentially increase their capability to regenerate cardiac tissue; in vivo studies are needed to confirm our in vitro findings. © 2018 Society for Endocrinology.

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

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2012-01-01

    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...... solution to the global fishery crisis, the MSC seems to be better tuned to the creation of a market for ‘sustainable fish’ rather than ‘sustainable fisheries’....

  10. Confirming the Revised C-Terminal Domain of the MscL Crystal Structure

    OpenAIRE

    Maurer, Joshua A.; Elmore, Donald E.; Clayton, Daniel; Xiong, Li; Lester, Henry A.; Dougherty, Dennis A.

    2008-01-01

    The structure of the C-terminal domain of the mechanosensitive channel of large conductance (MscL) has generated significant controversy. As a result, several structures have been proposed for this region: the original crystal structure (1MSL) of the Mycobacterium tuberculosis homolog (Tb), a model of the Escherichia coli homolog, and, most recently, a revised crystal structure of Tb-MscL (2OAR). To understand which of these structures represents a physiological conformation, we measured the ...

  11. Aiming for outstanding: Action research from students of the MSc in the Teaching of Psychology

    OpenAIRE

    Lintern, Fiona; Davies, Jamie; McGinty, Andrew; Fisher, Jeannine

    2014-01-01

    The first cohort of a new MSc programme is due to complete the course in August 2014. During the three-year online course students conduct several pieces of action research in their classrooms. There is little research specifically related classroom practice in the pre-tertiary psychology classroom. The following describes the rationale and context of the MSc in the Teaching of Psychology and reports on three students’ final year research. The first considers the benefits of Psychology Applie...

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Elizabeth J. Wright

    2016-01-01

    Full Text Available Background. Mesenchymal stem cells (MSCs and glucagon-like peptide-1 (GLP-1 are being tested as treatment strategies for myocardial infarction (MI; however, their mechanisms in the heart are not fully understood. Methods. We examined the effects of MSCs, either native, or engineered to secrete 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 CellBeads-MSC + GLP-1 and sacrificed at one or four weeks following MI. Results. MSC + GLP-1 conditioned media demonstrated antiapoptotic effects on ischaemic human cardiomyocytes in vitro. In vivo, qRT-PCR revealed large changes in the expression of several genes involved in extracellular matrix remodeling, which 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.

  14. Finding and tracing human MSC in 3D microenvironments with the photoconvertible protein Dendra2

    Science.gov (United States)

    Caires, Hugo R.; Gomez-Lazaro, Maria; Oliveira, Carla M.; Gomes, David; Mateus, Denisa D.; Oliveira, Carla; Barrias, Cristina C.; Barbosa, Mário A.; Almeida, Catarina R.

    2015-05-01

    Mesenchymal Stem/Stromal Cells (MSC) are a promising cell type for cell-based therapies - from tissue regeneration to treatment of autoimmune diseases - due to their capacity to migrate to damaged tissues, to differentiate in different lineages and to their immunomodulatory and paracrine properties. Here, a simple and reliable imaging technique was developed to study MSC dynamical behavior in natural and bioengineered 3D matrices. Human MSC were transfected to express a fluorescent photoswitchable protein, Dendra2, which was used to highlight and follow the same group of cells for more than seven days, even if removed from the microscope to the incubator. This strategy provided reliable tracking in 3D microenvironments with different properties, including the hydrogels Matrigel and alginate as well as chitosan porous scaffolds. Comparison of cells mobility within matrices with tuned physicochemical properties revealed that MSC embedded in Matrigel migrated 64% more with 5.2 mg protein/mL than with 9.6 mg/mL and that MSC embedded in RGD-alginate migrated 51% faster with 1% polymer concentration than in 2% RGD-alginate. This platform thus provides a straightforward approach to characterize MSC dynamics in 3D and has applications in the field of stem cell biology and for the development of biomaterials for tissue regeneration.

  15. β3-Adrenergic Regulation of EPC Features Through Manipulation of the Bone Marrow MSC Niche.

    Science.gov (United States)

    Vafaei, Rana; Nassiri, Seyed Mahdi; Siavashi, Vahid

    2017-12-01

    Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow, however, biological features of this niche are still not fully understood. Given the interactions of MSCs with endothelial cells in different tissues, bone marrow MSC niche may influence the biological features of endothelial progenitor cells (EPCs). To understand the role of the sympathetic nervous system in regulation of the MSC niche, we examined whether the manipulation of the MSC niche via β3-adrenergic signals will affect EPC features. A selective β3 agonist (BRL37344) or a β3 antagonist (SR59230A) was administered in mice for 2 weeks to determine the potential effects of these regimens on the population of CD133 + stem cells in the bone marrow. Then, bone marrow-derived MSCs and EPCs were harvested and expanded from the mice to examine the effect of changes in the MSC niche on EPC features. Improved MSC colony forming potency with increased bone marrow stromal cell-derived factor 1 (SDF-1) (also known as C-X-C motif chemokine 12 [CXCL12]) expression was shown as a result of intensification of the bone marrow adrenergic signals through BRL37344 injection. On the other hand, the blockage of these signals limited the expression level of SDF-1 and resulted in bone marrow enrichment of CD133 + cells. Manipulation of the MSC niche and decreased SDF-1 expression via SR59230A injection also prompted EPCs to form more colonies with augmented proliferation and differentiation capacity. Overall, our results indicate that the β3-adrenergic signals regulate the MSC niche, thereby resulting in modulation of EPC biological features. J. Cell. Biochem. 118: 4753-4761, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Umbilical cord mesenchymal stem cell (UC-MSC) transplantations for cerebral palsy

    Science.gov (United States)

    Dong, Huajiang; Li, Gang; Shang, Chongzhi; Yin, Huijuan; Luo, Yuechen; Meng, Huipeng; Li, Xiaohong; Wang, Yali; Lin, Ling; Zhao, Mingliang

    2018-01-01

    This study reports a case of a 4-year-old boy patient with abnormalities of muscle tone, movement and motor skills, as well as unstable gait leading to frequent falls. The results of the electroencephalogram (EEG) indicate moderately abnormal EEG, accompanied by irregular seizures. Based on these clinical characteristics, the patient was diagnosed with cerebral palsy (CP) in our hospital. In this study, the patient was treated with umbilical cord mesenchymal stem cell (UC-MSC) transplantation therapy. This patient received UC-MSC transplantation 3 times (5.3*107) in total. After three successive cell transplantations, the patient recovered well and showed obvious improvements in EEG and limb strength, motor function, and language expression. However, the improvement in intelligence quotient (IQ) was less obvious. These results indicate that UC-MSC transplantation is a promising treatment for cerebral palsy. PMID:29636880

  17. Effects of platelet rich plasma and chondrocyte co-culture on MSC chondrogenesis, hypertrophy and pathological responses

    OpenAIRE

    Ramezanifard, Rouhallah; Kabiri, Mahboubeh; Hanaee Ahvaz, Hana

    2017-01-01

    Regarding the inadequate healing capability of cartilage tissue, cell-based therapy is making the future of cartilage repair and regeneration. Mesenchymal stem cells (MSC) have shown great promise in cartilage regeneration. However, a yet-unresolved issue is the emergence of hypertrophic and pathologic markers during in vitro MSC chondrogenesis. Articular chondrocytes (AC) can suppress the undesired hypertrophy when co-cultured with MSC. On the other hand, platelet rich plasma (PRP), is consi...

  18. 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...

  19. Results of scatterometer systems analysis for NASA/MSC Earth Observation Sensor Evaluation Program.

    Science.gov (United States)

    Krishen, K.; Vlahos, N.; Brandt, O.; Graybeal, G.

    1971-01-01

    Radar scatterometers have applications in the NASA/MSC Earth Observation Aircraft Program. Over a period of several years, several missions have been flown over both land and ocean. In this paper a system evaluation of the NASA/MSC 13.3-GHz Scatterometer System is presented. The effects of phase error between the Scatterometer channels, antenna pattern deviations, aircraft attitude deviations, environmental changes, and other related factors such as processing errors, system repeatability, and propeller modulation, were established. Furthermore, the reduction in system errors and calibration improvement was investigated by taking into account these parameter deviations. Typical scatterometer data samples are presented.

  20. 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

  1. Further Developments on Optimum Structural Design Using MSC/Nastran and Sequential Quadratic Programming

    DEFF Research Database (Denmark)

    Holzleitner, Ludwig

    1996-01-01

    , here the shape of two dimensional parts with different thickness areas will be optimized. As in the previos paper, a methodology for structural optimization using the commercial finite element package MSC/NASTRAN for structural analysis is described. Three different methods for design sensitivity......This work is closely connected to the paper: K.G. MAHMOUD, H.W. ENGL and HOLZLEITNER: "OPTIMUM STRUCTURAL DESIGN USING MSC/NASTRAN AND SEQUENTIAL QUADRATIC PROGRAMMING", Computers & Structures, Vol. 52, No. 3, pp. 437-447, (1994). In contrast to that paper, where thickness optimization is described...

  2. Phenotypic, Functional, and Safety Control at Preimplantation Phase of MSC-Based Therapy

    Science.gov (United States)

    Lech, Wioletta; Figiel-Dabrowska, Anna; Drela, Katarzyna; Obtulowicz, Patrycja; Noszczyk, Bartlomiej Henryk; Buzanska, Leonora

    2016-01-01

    Mesenchymal stem cells (MSC) exhibit enormous heterogeneity which can modify their regenerative properties and therefore influence therapeutic effectiveness as well as safety of these cells transplantation. In addition the high phenotypic plasticity of MSC population makes it enormously sensitive to any changes in environmental properties including fluctuation in oxygen concentration. We have shown here that lowering oxygen level far below air atmosphere has a beneficial impact on various parameters characteristic for umbilical cord Wharton Jelly- (WJ-) MSC and adipose tissue- (AD-) derived MSC cultures. This includes their cellular composition, rate of proliferation, and maintenance of stemness properties together with commitment to cell differentiation toward mesodermal and neural lineages. In addition, the culture genomic stability increased significantly during long-term cell passaging and eventually protected cells against spontaneous transformation. Also by comparing of two routinely used methods of MSCs isolation (mechanical versus enzymatic) we have found substantial divergence arising between cell culture properties increasing along the time of cultivation in vitro. Thus, in this paper we highlight the urgent necessity to develop the more sensitive and selective methods for prediction and control cells fate and functioning during the time of growth in vitro. PMID:27651796

  3. Therapeutic use of human mesenchymal stem cells (MSC) for the treatment of radio-induced diseases

    International Nuclear Information System (INIS)

    Mouiseddine, Moubarak

    2008-05-01

    Ionising radiation can induce toxic effects on body. They provoke physiological modifications of tissues and organs which can be lethal. Total body irradiation or local abdominal irradiation can induce serious complications. Intestine is the first tissue concerned by these side effects. Radiation induces malabsorption of the intestine and lost of it integrity. Radio-induced physiopathological effects on intestine could lead to distant effects on other tissues and organs such as liver. The actual treatments have a limited efficiency or are not adapted to gastrointestinal damages. Indeed, in this type of lesions, the heterogeneous systems which are concerned and the gravity of lesions complicates the medical care. Our purpose is to show that cell therapy using human mesenchymal stem cells (MSC) constitutes resolution in this type of illness. The works which are presented in this thesis show that MSC are multi-potent and have heterogeneous expression of molecules. These cells are able to establish themselves in many organs and tissues after injection into irradiated body. Thus we have shown that MSC can prevent the small intestine from radio-induced damages. Indeed we demonstrate that through their actions on gut, MSC can indirectly restore hepatic integrity. (author)

  4. Post-MSc technological design (PDEng) traineeships by Dutch universities of technology catalyse industrial innovation

    NARCIS (Netherlands)

    Swinkels, P.L.J.

    2015-01-01

    The two-year post-MSc technological design traineeships organized by the Dutch Universities of Technology, and leading to the Professional Doctorate in Engineering (PDEng) degree, are still going strong after 28 years of existence. In 1986 the Dutch government and the Dutch industry - both aiming to

  5. 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. © FASEB.

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

    Science.gov (United States)

    Ribot, Emeline J; Gaudet, Jeffrey M; Chen, Yuhua; Gilbert, Kyle M; Foster, Paula J

    2014-01-01

    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.

  7. Matrix metalloproteinase-1 facilitates MSC migration via cleavage of IGF-2/IGFBP2 complex.

    Science.gov (United States)

    Guan, Shou P; Lam, Alan T L; Newman, Jennifer P; Chua, Kevin L M; Kok, Catherine Y L; Chong, Siao T; Chua, Melvin L K; Lam, Paula Y P

    2018-01-01

    The specific mechanism underlying the tumor tropism of human mesenchymal stem cells (MSCs) for cancer is not well defined. We previously showed that the migration potential of MSCs correlated with the expression and protease activity of matrix metalloproteinase (MMP)-1. Furthermore, highly tumor-tropic MSCs expressed higher levels of MMP-1 and insulin-like growth factor (IGF)-2 than poorly migrating MSCs. In this study, we examined the functional roles of IGF-2 and MMP-1 in mediating the tumor tropism of MSCs. Exogenous addition of either recombinant IGF-2 or MMP-1 could stimulate MSC migration. The correlation between IGF-2, MMP-1 expression, and MSC migration suggests that MMP-1 may play a role in regulating MSC migration via the IGF-2 signaling cascade. High concentrations of IGF binding proteins (IGFBPs) can inhibit IGF-stimulated functions by blocking its binding to its receptors and proteolysis of IGFBP is an important mechanism for the regulation of IGF signaling. We thus hypothesized that MMP-1 acts as an IGFBP2 proteinase, resulting in the cleavage of IGF-2/IGFBP2 complex and extracellular release of free IGF-2. Indeed, our results showed that conditioned media from highly migrating MSCs, which expressed high levels of MMP-1, cleaved the IGF-2/IGFBP2 complex. Taken together, these results showed that the MMP-1 secreted by highly tumor-tropic MSCs cleaved IGF-2/IGFBP2 complex. Free IGF-2 released from the complex may facilitate MSC migration toward tumor.

  8. Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations

    NARCIS (Netherlands)

    Deplazes, Evelyne; Louhivuori, Martti; Jayatilaka, Dylan; Marrink, Siewert J.; Corry, Ben

    The mechanosensitive channel of large conductance (MscL) has become a model system in which to understand mechanosensation, a process involved in osmoregulation and many other physiological functions. While a high resolution closed state structure is available, details of the open structure and the

  9. Comparing estimates of EMEP MSC-Wand UFORE models in air pollutant reduction by urban trees

    Czech Academy of Sciences Publication Activity Database

    Guidolotti, G.; Salvatio, M.; Calfapietra, Carlo

    2016-01-01

    Roč. 23, č. 19 (2016), s. 19541-19550 ISSN 0944-1344 Institutional support: RVO:67179843 Keywords : i-Tree * UFORE, EMEP/MSC-Wmodel * urban forest * atmospheric pollutants * O3 * NO2 * PM10 Subject RIV: EF - Botanics Impact factor: 2.741, year: 2016

  10. Phenotypic, Functional, and Safety Control at Preimplantation Phase of MSC-Based Therapy.

    Science.gov (United States)

    Lech, Wioletta; Figiel-Dabrowska, Anna; Sarnowska, Anna; Drela, Katarzyna; Obtulowicz, Patrycja; Noszczyk, Bartlomiej Henryk; Buzanska, Leonora; Domanska-Janik, Krystyna

    2016-01-01

    Mesenchymal stem cells (MSC) exhibit enormous heterogeneity which can modify their regenerative properties and therefore influence therapeutic effectiveness as well as safety of these cells transplantation. In addition the high phenotypic plasticity of MSC population makes it enormously sensitive to any changes in environmental properties including fluctuation in oxygen concentration. We have shown here that lowering oxygen level far below air atmosphere has a beneficial impact on various parameters characteristic for umbilical cord Wharton Jelly- (WJ-) MSC and adipose tissue- (AD-) derived MSC cultures. This includes their cellular composition, rate of proliferation, and maintenance of stemness properties together with commitment to cell differentiation toward mesodermal and neural lineages. In addition, the culture genomic stability increased significantly during long-term cell passaging and eventually protected cells against spontaneous transformation. Also by comparing of two routinely used methods of MSCs isolation (mechanical versus enzymatic) we have found substantial divergence arising between cell culture properties increasing along the time of cultivation in vitro. Thus, in this paper we highlight the urgent necessity to develop the more sensitive and selective methods for prediction and control cells fate and functioning during the time of growth in vitro.

  11. 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

  12. European MSc Programs in Nuclear Sciences - To meet the Need of Stakeholders

    International Nuclear Information System (INIS)

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

    2009-01-01

    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 (3x10 ECTS credits), three specialist modules (3x10 ECTS credits) and a research project (1x60 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.

  13. Injectable MMP-sensitive alginate hydrogels as hMSC delivery systems.

    Science.gov (United States)

    Fonseca, Keila B; Gomes, David B; Lee, Kangwon; Santos, Susana G; Sousa, Aureliana; Silva, Eduardo A; Mooney, David J; Granja, Pedro L; Barrias, Cristina C

    2014-01-13

    Hydrogels with the potential to provide minimally invasive cell delivery represent a powerful tool for tissue-regeneration therapies. In this context, entrapped cells should be able to escape the matrix becoming more available to actively participate in the healing process. Here, we analyzed the performance of proteolytically degradable alginate hydrogels as vehicles for human mesenchymal stem cells (hMSC) transplantation. Alginate was modified with the matrix metalloproteinase (MMP)-sensitive peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG), which did not promote dendritic cell maturation in vitro, neither free nor conjugated to alginate chains, indicating low immunogenicity. hMSC were entrapped within MMP-sensitive and MMP-insensitive alginate hydrogels, both containing cell-adhesion RGD peptides. Softer (2 wt % alginate) and stiffer (4 wt % alginate) matrices were tested. When embedded in a Matrigel layer, hMSC-laden MMP-sensitive alginate hydrogels promoted more extensive outward cell migration and invasion into the tissue mimic. In vivo, after 4 weeks of subcutaneous implantation in a xenograft mouse model, hMSC-laden MMP-sensitive alginate hydrogels showed higher degradation and host tissue invasion than their MMP-insensitive equivalents. In both cases, softer matrices degraded faster than stiffer ones. The transplanted hMSC were able to produce their own collagenous extracellular matrix, and were located not only inside the hydrogels, but also outside, integrated in the host tissue. In summary, injectable MMP-sensitive alginate hydrogels can act as localized depots of cells and confer protection to transplanted cells while facilitating tissue regeneration.

  14. European MSc Programs in Nuclear Sciences-To meet the need of stakeholders

    International Nuclear Information System (INIS)

    Skipperud, L.; Salbu, B.; Priest, N.; Garelick, H.; Tamponnet, C.; Abbott, A.; Mitchell, P.

    2011-01-01

    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 radio chemists and radiation protection dosimetry experts. 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 x 10 ECTS credits), three specialist modules (3 x 10 ECTS credits) and a research project (1 x 60 ECTS credits). The courses should be aimed, not only to fill the identified European post-graduate 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.

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

    Directory of Open Access Journals (Sweden)

    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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  18. Effectiveness of cross-border knowledge transfer in Malaysian MSC status corporations

    Directory of Open Access Journals (Sweden)

    Aaron Sow Yee Pook

    2017-03-01

    Full Text Available Knowledge has become the key asset for the economy to gain competitiveness as more and more countries have shifted or are shifting towards knowledge-based economy, no exception for Malaysia. In order to acquire and transfer technology and/or knowledge from overseas to Malaysia, Multimedia Super Corridor (MSC has been proposed. However, research focuses on cross-border knowledge transfer especially in the context of MSC status corporations in Malaysia is still limited. The factors that affect the effectiveness of cross-border knowledge transfer will be determined and presented in this paper. Quantitative approach has been adopted in this study. The findings of this study show that knowledge characteristics (KC and network characteristics (NC have positive significant relationship with cross-border knowledge transfer. The effects context towards KC and NC will also be examined in this study.

  19. 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. .

  20. 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...

  1. Water Dynamics and Dewetting Transitions in the Small Mechanosensitive Channel MscS

    Science.gov (United States)

    Anishkin, Andriy; Sukharev, Sergei

    2004-01-01

    The dynamics of confined water in capillaries and nanotubes suggests that gating of ion channels may involve not only changes of the pore geometry, but also transitions between water-filled and empty states in certain locations. The recently solved heptameric structure of the small mechanosensitive channel of Escherichia coli, MscS, has revealed a relatively wide (7–15 Å) yet highly hydrophobic transmembrane pore. Continuum estimations based on the properties of pore surface suggest low conductance and a thermodynamic possibility of dewetting. To test the predictions we performed molecular dynamics simulations of MscS filled with flexible TIP3P water. Irrespective to the initial conditions, several independent 6-ns simulations converged to the same stable state with the pore water-filled in the wider part, but predominantly empty in the narrow hydrophobic part, displaying intermittent vapor-liquid transitions. The polar gain-of-function substitution L109S in the constriction resulted in a stable hydration of the entire pore. Steered passages of Cl− ions through the narrow part of the pore consistently produced partial ion dehydration and required a force of 200–400 pN to overcome an estimated barrier of 10–20 kcal/mole, implying negligibly low conductance. We conclude that the crystal structure of MscS does not represent an open state. We infer that MscS gate, which is similar to that of the nicotinic ACh receptor, involves a vapor-lock mechanism where limited changes of geometry or surface polarity can locally switch the regime between water-filled (conducting) and empty (nonconducting) states. PMID:15111405

  2. Comparison of MSC-Neurogenin1 administration modality in MCAO rat model

    Directory of Open Access Journals (Sweden)

    Shin Dong Hoon

    2016-12-01

    Full Text Available Intracerebral (IC grafting of mesenchymal stem cells (MSCs is not currently used in humans due to its potential complications. On the other hand, intra-arterial (IA administration can be facilitated for engrafting of intensifed MSCs in the injured human brain. The study is designed to compare the two methods of MSC administration using IA and IC routes through the parameters of behavior, infarct volume, cell distribution, and MSC identification. An ischemic stroke model was generated in Sprague Dawley male rats. This experiment used MSCs/Ngn1 that express Neurogenin1 (Ngn1 to ensure grafted MSC maintenance. MSCs/Ngn1 or normal saline was administrated via the IC or IA route on day 3. All animals were randomly assigned into four groups (five rats in each group: IC-control, IA-control, IC-MSCs/Ngn1, or IA-MSCs/Ngn1. Motor behaviors, infarct volume, and distribution of superparamagnetic iron oxide (SPIO-labeled cells on magnetic resonance imaging (MRI were compared from each group. There were no baseline differencess in motor behaviors or infarct volume between IC-MSCs/Ngn1 and IA-MSCs/Ngn1. Hovever, the IA-MSCs/Ngn1 group showed the greatest recovery on Rotarod testing and adhesive removal tests (p = 0.003 and p = 0.009 vs. IC-MSCs/Ngn1, respectively. The IA-MSCs/Ngn1 group also had more evenly distributed SPIO-labeled cells on MRI. The results suggest that IA administration is likely to be benefcial for humans based on its ability to improve behavioral outcomes and ensure even MSC engrafting.

  3. 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

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

    OpenAIRE

    Ribot, Emeline J; Gaudet, Jeffrey M; Chen, Yuhua; Gilbert, Kyle M; Foster, Paula J

    2014-01-01

    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 migra...

  5. Comparing and contrasting Escherichia coli and Mycobacterium tuberculosis mechanosensitive channels (MscL) - New gain of function mutations in the loop region

    OpenAIRE

    Maurer, Joshua A.; Elmore, Donald E.; Lester, Henry A.; Dougherty, Dennis A.

    2000-01-01

    Sequence analysis of 35 putative MscL homologues was used to develop an optimal alignment for Escherichia coli and Mycobacterium tuberculosis MscL and to place these homologues into sequence subfamilies. By using this alignment, previously identified E. coli MscL mutants that displayed severe and very severe gain of function phenotypes were mapped onto the M. tuberculosis MscL sequence. Not all of the resulting M. tuberculosis mutants displayed a gain of function phenotype; for instance, norm...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Determining total sulfur content in coal by MSC radiometric sulfur meter

    Energy Technology Data Exchange (ETDEWEB)

    Czerw, B; Sikora, T; Golebiowski, W

    1976-01-01

    The MSC radiometric sulfur meter is used to determine total sulfur content in brown and black coals. Sulfur content is determined by measuring intensity of radiation beam which has travelled through a coal sample with the optimum constant surface mass. Construction of the MSC, consisting of a measuring head and the electronic measuring system, is shown in a scheme. AM-241 (with activity of 50 mCi) is the source of radiation. Energy of 25.3 keV (tin disc) is selected as the optimum. The SSU-70 probe with NaJ/Tl crystal is the radiation detector. The black coal sample weighs 10 g and the brown coal sample weighs 18 g. Duration of sulfur determination is 10 min. Error of sulfur determination ranges from plus or minus 0.2% to 0.3%. The results of operational tests of MSC radiometric sulfur meters in black and brown coal mines are discussed. Accuracy of measurement is shown in 5 tables. (8 refs.)

  8. 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. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

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

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    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

  11. 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.

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

    Science.gov (United States)

    Giallongo, Cesarina; Romano, Alessandra; Parrinello, Nunziatina Laura; La Cava, Piera; Brundo, Maria Violetta; Bramanti, Vincenzo; Stagno, Fabio; Vigneri, Paolo; Chiarenza, Annalisa; Palumbo, Giuseppe Alberto; Tibullo, Daniele; Di Raimondo, Francesco

    2016-01-01

    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.

  13. S. aureus MscL is a pentamer in vivo but of variable stoichiometries in vitro: implications for detergent-solubilized membrane proteins.

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    Michael R Dorwart

    Full Text Available While the bacterial mechanosensitive channel of large conductance (MscL is the best studied biological mechanosensor and serves as a paradigm for how a protein can sense and respond to membrane tension, the simple matter of its oligomeric state has led to debate, with models ranging from tetramers to hexamers. Indeed, two different oligomeric states of the bacterial mechanosensitive channel MscL have been resolved by X-ray crystallography: The M. tuberculosis channel (MtMscL is a pentamer, while the S. aureus protein (SaMscL forms a tetramer. Because several studies suggest that, like MtMscL, the E. coli MscL (EcoMscL is a pentamer, we re-investigated the oligomeric state of SaMscL. To determine the structural organization of MscL in the cell membrane we developed a disulfide-trapping approach. Surprisingly, we found that virtually all SaMscL channels in vivo are pentameric, indicating this as the physiologically relevant and functional oligomeric state. Complementing our in vivo results, we purified SaMscL and assessed its oligomeric state using three independent approaches (sedimentation equilibrium centrifugation, crosslinking, and light scattering and established that SaMscL is a pentamer when solubilized in Triton X-100 and C(8E(5 detergents. However, performing similar experiments on SaMscL solubilized in LDAO, the detergent used in the crystallographic study, confirmed the tetrameric oligomerization resolved by X-ray crystallography. We further demonstrate that this stoichiometric shift is reversible by conventional detergent exchange experiments. Our results firmly establish the pentameric organization of SaMscL in vivo. Furthermore they demonstrate that detergents can alter the subunit stoichiometry of membrane protein complexes in vitro; thus, in vivo assays are necessary to firmly establish a membrane protein's true functionally relevant oligomeric state.

  14. S. aureus MscL is a pentamer in vivo but of variable stoichiometries in vitro: implications for detergent-solubilized membrane proteins.

    Science.gov (United States)

    Dorwart, Michael R; Wray, Robin; Brautigam, Chad A; Jiang, Youxing; Blount, Paul

    2010-12-07

    While the bacterial mechanosensitive channel of large conductance (MscL) is the best studied biological mechanosensor and serves as a paradigm for how a protein can sense and respond to membrane tension, the simple matter of its oligomeric state has led to debate, with models ranging from tetramers to hexamers. Indeed, two different oligomeric states of the bacterial mechanosensitive channel MscL have been resolved by X-ray crystallography: The M. tuberculosis channel (MtMscL) is a pentamer, while the S. aureus protein (SaMscL) forms a tetramer. Because several studies suggest that, like MtMscL, the E. coli MscL (EcoMscL) is a pentamer, we re-investigated the oligomeric state of SaMscL. To determine the structural organization of MscL in the cell membrane we developed a disulfide-trapping approach. Surprisingly, we found that virtually all SaMscL channels in vivo are pentameric, indicating this as the physiologically relevant and functional oligomeric state. Complementing our in vivo results, we purified SaMscL and assessed its oligomeric state using three independent approaches (sedimentation equilibrium centrifugation, crosslinking, and light scattering) and established that SaMscL is a pentamer when solubilized in Triton X-100 and C(8)E(5) detergents. However, performing similar experiments on SaMscL solubilized in LDAO, the detergent used in the crystallographic study, confirmed the tetrameric oligomerization resolved by X-ray crystallography. We further demonstrate that this stoichiometric shift is reversible by conventional detergent exchange experiments. Our results firmly establish the pentameric organization of SaMscL in vivo. Furthermore they demonstrate that detergents can alter the subunit stoichiometry of membrane protein complexes in vitro; thus, in vivo assays are necessary to firmly establish a membrane protein's true functionally relevant oligomeric state.

  15. Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression.

    Science.gov (United States)

    Huang, Feng; Wang, Mei; Yang, Tingting; Cai, Jie; Zhang, Qiang; Sun, Zixuan; Wu, Xiaodan; Zhang, Xu; Zhu, Wei; Qian, Hui; Xu, Wenrong

    2014-11-01

    This study was designed to investigate the role of PDGF-DD secreted by gastric cancer-derived mesenchymal stem cells (GC-MSCs) in human gastric cancer progression. Gastric cancer cells were indirectly co-cultured with GC-MSCs in a transwell system. The growth and migration of gastric cancer cells were evaluated by cell colony formation assay and transwell migration assay, respectively. The production of PDGF-DD in GC-MSCs was determined by using Luminex and ELISA. Neutralization of PDGFR-β by su16f and siRNA interference of PDGF-DD in GC-MSCs was used to demonstrate the role of PDGF-DD produced by GC-MSCs in gastric cancer progression. GC-MSC conditioned medium promoted gastric cancer cell proliferation and migration in vitro and in vivo. Co-culture with GC-MSCs increased the phosphorylation of PDGFR-β in SGC-7901 cells. Neutralization of PDGFR-β by su16f blocked the promoting role of GC-MSC conditioned medium in gastric cancer cell proliferation and migration. Recombinant PDGF-DD duplicated the effects of GC-MSC conditioned medium on gastric cancer cells. Knockdown of PDGF-DD in GC-MSCs abolished its effects on gastric cancer cells in vitro and in vivo. PDGF-DD secreted by GC-MSCs is capable of promoting gastric cancer cell progression in vitro and in vivo. Targeting the PDGF-DD/PDGFR-β interaction between MSCs and gastric cancer cells may represent a novel strategy for gastric cancer therapy.

  16. Use of MSC/NASTRAN for the thermal analysis of the Space Shuttle Orbiter braking system

    Science.gov (United States)

    Shu, James; Mccann, David

    1987-01-01

    A description is given of the thermal modeling and analysis effort being conducted to investigate the transient temperature and thermal stress characteristics of the Space Shuttle Orbiter brake components and subsystems. Models are constructed of the brake stator as well as of the entire brake assembly to analyze the temperature distribution and thermal stress during the landing and braking process. These investigations are carried out on a UNIVAC computer system with MSC/NASTRAN Version 63. Analytical results and solution methods are presented and comparisons are made with SINDA results.

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

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    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.

  18. Effect of Bioactive Materials Modified with Chondroitin Sulfate on Human MSC =

    Science.gov (United States)

    De La Torre Torres, Jessica Elizabeth

    In this project chondroitin sulfate (CS) and growth factors were studied for their effect on hMSC in biomaterials. First, the effect of these biomolecules was tested in solution. Then, two kinds of biomaterials were created: bioactive surfaces for enhancing bioactivity of implantable devices and bioactive hydrogels which can be used as 3D scaffolds for cell encapsulation and delivery. A pro-survival effect of the growth factors studied in this project (epidermal growth factor, vascular endothelial growth factor and fibroblast growth factor) was not observed when tested in solution, therefore the project further focused on CS effect only. Interestingly, CS did not affect cell growth in media containing serum, while inducing cell detachment from substrate in serum free conditions. For the bioactive surfaces construction, CS was grafted to either an amine-rich plasmapolymerized coating created on polyethylene terephthalate (PET) films (further referred as LP) or to commercial cell culture plates functionalized with amino groups. The bioactive surfaces were characterized by different techniques such as contact angle, atomic force microscopy, Orange II dye and Toluidine Blue O dye colorimetric assays (for amino group and CS quantification respectively) and finally, cell culture experiments (adhesion, growth and survival). Results confirmed the presence of CS grafted on both substrates. Commercial amine plates grafted almost five times more CS compared to LP. This rendered the surface antifouling for proteins and cells as confirmed by protein adsorption and cell culture assays. Cell culture assays on bioactive surfaces based on LP demonstrated improved cell adhesion and growth when compared to tissue culture plates or bare PET films in serum containing conditions. Chitosan based hydrogels containing CS at a concentration of 500 mug/ml resulted in a cohesive hydrogel which supported hMSC viability up to 7 days. However increasing CS concentration to high level such as

  19. Breaking the hydrophobicity of the MscL pore: insights into a charge-induced gating mechanism.

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    Balasubramanian Chandramouli

    Full Text Available The mechanosensitive channel of large conductance (MscL is a protein that responds to membrane tension by opening a transient pore during osmotic downshock. Due to its large pore size and functional reconstitution into lipid membranes, MscL has been proposed as a promising artificial nanovalve suitable for biotechnological applications. For example, site-specific mutations and tailored chemical modifications have shown how MscL channel gating can be triggered in the absence of tension by introducing charged residues at the hydrophobic pore level. Recently, engineered MscL proteins responsive to stimuli like pH or light have been reported. Inspired by experiments, we present a thorough computational study aiming at describing, with atomistic detail, the artificial gating mechanism and the molecular transport properties of a light-actuated bacterial MscL channel, in which a charge-induced gating mechanism has been enabled through the selective cleavage of photo-sensitive alkylating agents. Properties such as structural transitions, pore dimension, ion flux and selectivity have been carefully analyzed. Besides, the effects of charge on alternative sites of the channel with respect to those already reported have been addressed. Overall, our results provide useful molecular insights into the structural events accompanying the engineered MscL channel gating and the interplay of electrostatic effects, channel opening and permeation properties. In addition, we describe how the experimentally observed ionic current in a single-subunit charged MscL mutant is obtained through a hydrophobicity breaking mechanism involving an asymmetric inter-subunit motion.

  20. Fibrous hyaluronic acid hydrogels that direct MSC chondrogenesis through mechanical and adhesive cues.

    Science.gov (United States)

    Kim, Iris L; Khetan, Sudhir; Baker, Brendon M; Chen, Christopher S; Burdick, Jason A

    2013-07-01

    Electrospinning has recently gained much interest due to its ability to form scaffolds that mimic the nanofibrous nature of the extracellular matrix, such as the size and depth-dependent alignment of collagen fibers within hyaline cartilage. While much progress has been made in developing bulk, isotropic hydrogels for tissue engineering and understanding how the microenvironment of such scaffolds affects cell response, these effects have not been extensively studied in a nanofibrous system. Here, we show that the mechanics (through intrafiber crosslink density) and adhesivity (through RGD density) of electrospun hyaluronic acid (HA) fibers significantly affect human mesenchymal stem cell (hMSC) interactions and gene expression. Specifically, hMSC spreading, proliferation, and focal adhesion formation were dependent on RGD density, but not on the range of fiber mechanics investigated. Moreover, traction-mediated fiber displacements generally increased with more adhesive fibers. The expression of chondrogenic markers, unlike trends in cell spreading and cytoskeletal organization, was influenced by both fiber mechanics and adhesivity, in which softer fibers and lower RGD densities generally enhanced chondrogenesis. This work not only reveals concurrent effects of mechanics and adhesivity in a fibrous context, but also highlights fibrous HA hydrogels as a promising scaffold for future cartilage repair strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

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    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.

  2. MSC/NASTRAN ''expert'' techniques developed and applied to the TFTR poloidal field coils

    International Nuclear Information System (INIS)

    O'Toole, J.A.

    1986-01-01

    The TFTR poloidal field (PF) coils are being analyzed by PPPL and Grumman using MSC/NASTRAN as a part of an overall effort to establish the absolute limiting conditions of operation for TFTR. Each of the PF coils will be analyzed in depth, using a detailed set of finite element models. Several of the models developed are quite large because each copper turn, as well as its surrounding insulation, was modeled using solid elements. Several of the finite element models proved large enough to tax the capabilities of the National Magnetic Fusion Energy Computer Center (NMFECC), specifically disk storage space. To allow the use of substructuring techniques with their associated data bases for the larger models, it became necessary to employ certain infrequently used MSC/NASTRAN ''expert'' techniques. The techniques developed used multiple data bases and data base sets to divide each problem into a series of computer runs. For each run, only the data required was kept on active disk space, the remainder being placed in inactive ''FILEM'' storage, thus, minimizing active disk space required at any time and permitting problem solution using the NMFECC. A representative problem using the TFTR OH-1 coil global model provides an example of the techniques developed. The special considerations necessary to obtain proper results are discussed

  3. The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice

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    Fakharzadeh S

    2014-08-01

    Full Text Available Saideh Fakharzadeh,1 Mohammad Ali Sahraian,2 Maryam Hafizi,1 Somayeh Kalanaky,1 Zahra Masoumi,1 Mehdi Mahdavi,1 Nasser Kamalian,3 Alireza Minagar,4 Mohammad Hassan Nazaran1 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Pathology, Medical School of Tehran University of Medical Sciences, Tehran, Iran; 4Department of Neurology, LSU Health Sciences Centre, Shreveport, LA, USA Purpose: Currently approved therapies for multiple sclerosis (MS at best only slow down its progression. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In the present study, for the first time we evaluated the therapeutic potential of MSc1 nanocomplex, which was designed based on novel nanochelating technology. Materials and methods: MSc1 cell-protection capacity, with and without iron bond, was evaluated against hydrogen peroxide (H2O2-induced oxidative stress in cultured rat pheochromocytoma-12 cells. The ability of MSc1 to maintain iron bond at pH ranges of 1–7 was evaluated. Nanocomplex toxicity was examined by estimating the intraperitoneal median lethal dose (LD50. Experimental autoimmune encephalomyelitic mice were injected with MSc1 14 days after disease induction, when the clinical symptoms appeared. The clinical score, body weight, and disease-induced mortality were monitored until day 54. In the end, after collecting blood samples for assessing hemoglobin and red blood cell count, the brains and livers of the mice were isolated for hematoxylin and eosin staining and analysis of iron content, respectively. Results: The results showed that MSc1 prevented H2O2-induced cell death even after binding with iron, and it preserved its bond with iron constant at pH ranges 1–7. The nanocomplex intraperitoneal LD50 was 1,776.59 mg/kg. MSc1 prompted therapeutic

  4. 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, PTrx-1 vs. NS, PTrx-1 vs. hucMSC or NS, PTrx-1 vs. NS, PTrx-1 vs. hucMSC, PTrx-1 vs. NS, PTrx-1 vs. hucMSC, PTrx-1 vs. hucMSC or NS, PTrx-1 combines the merits of gene and cell therapy as a multifunctional radioprotector for ARI.

  5. Adaptive MscS gating in the osmotic permeability response in E. coli: the question of time.

    Science.gov (United States)

    Boer, Miriam; Anishkin, Andriy; Sukharev, Sergei

    2011-05-17

    Microorganisms adapt to osmotic downshifts by releasing small osmolytes through mechanosensitive (MS) channels. We want to understand how the small mechanosensitive channel's (MscS) activation and inactivation, both driven by membrane tension, optimize survival in varying hypoosmotic shock situations. By measuring light scattering with a stopped-flow device, we estimate bacterial swelling time as 30-50 ms. A partial solute equilibration follows within 150-200 ms, during which optical responses from cells with WT MscS deviate from those lacking MS channels. MscS opening rates estimated in patch clamp show the channels readily respond to tensions below the lytic limit with a time course faster than 20 ms and close promptly upon tension release. To address the role of the tension-insensitive inactivated state in vivo, we applied short, long, and two-step osmotic shock protocols to WT, noninactivating G113A, and fast-inactivating D62N mutants. WT and G113A showed a comparable survival in short 1 min 800 mOsm downshock experiments, but G113A was at a disadvantage under a long 60 min shock. Preshocking cells carrying WT MscS for 15 s to 15 min with a 200 mOsm downshift did not sensitize them to the final 500 mOsm drop in osmolarity of the second step. However, these two-step shocks induced death in D62N more than just a one-step 700 mOsm downshift. We conclude MscS is able to activate and exude osmolytes faster than lytic pressure builds inside the cell under abrupt shock. During prolonged shocks, gradual inactivation prevents continuous channel activity and assists recovery. Slow kinetics of inactivation in WT MscS ensures that mild shocks do not inactivate the entire population, leaving some protection should conditions worsen.

  6. Behavioral Evaluation of hMSC-GFP+ Transplantation in an Hemiparkinson Experimental Model in Wistar Rat

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    Jéssica Paola Alcázar Arzuza

    2017-05-01

    Full Text Available The effect of hMSCs-GFP+ transplantation was evaluated in an experimental model of Parkinson's disease (PD in 27 Wistar rats, or in three experimental groups: control (CON  n=7, injured (LES n=10 and transplanted (LES+T n=10. In order to evaluate the influence of the transplantation on the motor behavior, one month after the injury, rotation behavior induced by apomorphine, neurological test, transversal bar and SNpc cells positive to TH were developed. Using the Anova test, there was a decrease in the number of turns in transplanted animals (p=0.005 as well as in the neurological test (p=0.0004 and in the transverse bar that lead to this group in an intermediate position regarding LES and CON groups. There is a possible recovery of the transplantation-mediated nigroestriatal pathway of hMSC-GFP +.

  7. A new method for analyzing fluid-structure interaction using MSC/NASTRAN

    International Nuclear Information System (INIS)

    MacNeal, R.H.; Citerley, R.; Chargin, M.

    1979-01-01

    A popular method for analyzing compressible fluids in flexible containers is to represent the fluid by a three-dimensional finite element model in which the pressure is the unknown nodal point variable, and to represent the structure by another finite element model in which displacement components are the unknown nodal point variables. This method has the computational drawback that the matrix terms coupling the fluid to the structure are unsymmetric. This paper shows that symmetric fluid-structure coupling can be achieved if either the fluid or the structure is represented by its uncoupled vibrational modes, and if additional auxiliary variables are defined. The resulting system equations can be solved efficiently for the coupled vibration modes and for the coupled dynamic response by a general purpose finite element program, such as MSC/NASTRAN. (orig.)

  8. The modeling experience of fuel element units operation under MSC.MARC and MENTAT 2008R1

    International Nuclear Information System (INIS)

    Kulakov, G.; Kashirin, B.; Kosaurov, A.; Konovalov, Y.; Kuznetsov, A.; Medvedev, A.; Novikov, V.; Vatulin, A.

    2009-01-01

    MSC Software is leading developer of CAE-software in the world, so behaviour of fuel elements modeling with MSC.MARC use is of great practical importance. Behaviour of fuel elements usually is modeled in the elastic-viscous-plastic statement with account on fuel swelling during irradiation. For container type fuel elements contact interaction between fuel pellets and cladding or other parts of fuel element in top and bottom plugs must be in account. Results of simulated behaviour of various type fuel elements - container type fuel elements for PWR and RBMK reactors, dispersion type fuel elements for research reactors are presented. (authors)

  9. Functional properties of meat by-products and mechanically separated chicken (MSC) in a high-moisture model petfood system.

    Science.gov (United States)

    Rivera, J A; Sebranek, J G; Rust, R E

    2000-05-01

    Contributions to water retention capacity (% WRC) and texture changes were determined for pork by-products (lung lobes, kidneys), chicken viscera (head, feet and viscera) and mechanically separated chicken (MSC) as affected by pH and various salts in a high-moisture model system. The % WRC for meat by-products and MSC was increased by increased pH (4.5-6.8). Pork lungs and MSC had the highest % WRC (pmeat by-products. Meat by-product % WRC was not signifcantly (p>0.05) affected by salt (2%), phosphate (0.3%) or NaOH (0.075%). Chicken viscera had the lowest (pmeat by-products and MSC. Strong negative correlations (p<0.05) were obtained for texture with total collagen, soluble collagen and high ionic strength soluble (HIS) proteins. These results should be considered for product quality changes when these by-products are used in formulation of high moisture pet food products.

  10. 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

  11. MiR-9-5p promotes MSC migration by activating β-catenin signaling pathway.

    Science.gov (United States)

    Li, Xianyang; He, Lihong; Yue, Qing; Lu, Junhou; Kang, Naixin; Xu, Xiaojing; Wang, Huihui; Zhang, Huanxiang

    2017-07-01

    Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages, but the very limited number of cells that migrate to the damaged region strongly restricts their therapeutic applications. Full understanding of mechanisms regulating MSC migration will help to improve their migration ability and therapeutic effects. Increasing evidence shows that microRNAs play important roles in the regulation of MSC migration. In the present study, we reported that miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs with high migration ability. Overexpression of miR-9-5p promoted MSC migration, whereas inhibition of endogenous miR-9-5p decreased MSC migration. To elucidate the underlying mechanism, we screened the target genes of miR-9-5p and report for the first time that CK1α and GSK3β, two inhibitors of β-catenin signaling pathway, were direct targets of miR-9-5p in MSCs and that overexpression of miR-9-5p upregulated β-catenin signaling pathway. In line with these data, inhibition of β-catenin signaling pathway by FH535 decreased the miR-9-5p-promoted migration of MSCs, while activation of β-catenin signaling pathway by LiCl rescued the impaired migration of MSCs triggered by miR-9-5p inhibitor. Furthermore, the formation and distribution of focal adhesions as well as the reorganization of F-actin were affected by the expression of miR-9-5p. Collectively, these results demonstrate that miR-9-5p promotes MSC migration by upregulating β-catenin signaling pathway, shedding light on the optimization of MSCs for cell replacement therapy through manipulating the expression level of miR-9-5p. Copyright © 2017 the American Physiological Society.

  12. MSC transplantation: a promising therapeutic strategy to manage the onset and progression of diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Marcelo E Ezquer

    2012-01-01

    Full Text Available Currently, one of the main threats to public health is diabetes mellitus. Its most detrimental complication is diabetic nephropathy (DN, a clinical syndrome associated with kidney damage and an increased risk of cardiovascular disease. Irrespective of the type of diabetes, DN follows a well-known temporal course. The earliest detectable signs are microalbuminuria and histopathological changes including extracellular matrix deposition, glomerular basement membrane thickening, glomerular and mesangial expansion. Later on macroalbuminuria appears, followed by a progressive decline in glomerular filtration rate and the loss of glomerular podocytes, tubulointerstitial fibrosis, glomerulosclerosis and arteriolar hyalinosis. Tight glycemic and hypertension controls remain the key factors for preventing or arresting the progression of DN. Nevertheless, despite considerable educational effort to control the disease, a significant number of patients not only develop DN, but also progress to chronic kidney disease. Therefore, the availability of a strategy aimed to prevent, delay or revert DN would be highly desirable. In this article, we review the pathophysiological features of DN and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs. The perfect match between them, together with encouraging pre-clinical data available, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage DN onset and progression, not only because of the safety of this procedure, but mainly because of the renoprotective potential of MSCs.

  13. Silicone Substrate with Collagen and Carbon Nanotubes Exposed to Pulsed Current for MSC Osteodifferentiation

    Directory of Open Access Journals (Sweden)

    Daniyal Jamal

    2017-01-01

    Full Text Available Autologous human adipose tissue-derived mesenchymal stem cells (MSCs have the potential for clinical translation through their induction into osteoblasts for regeneration. Bone healing can be driven by biophysical stimulation using electricity for activating quiescent adult stem cells. It is hypothesized that application of electric current will enhance their osteogenic differentiation, and addition of conductive carbon nanotubes (CNTs to the cell substrate will provide increased efficiency in current transmission. Cultured MSCs were seeded and grown onto fabricated silicone-based composites containing collagen and CNT fibers. Chemical inducers, namely, glycerol phosphate, dexamethasone, and vitamin C, were then added to the medium, and pulsatile submilliampere electrical currents (about half mA for 5 cycles at 4 mHz, twice a week were applied for two weeks. Calcium deposition indicative of MSC differentiation and osteoblastic activity was quantified through Alizarin Red S and spectroscopy. It was found that pulsed current significantly increased osteodifferentiation on silicone-collagen films without CNTs. Under no external current, the presence of 10% (m/m CNTs led to a significant and almost triple upregulation of calcium deposition. Both CNTs and current parameters did not appear to be synergistic. These conditions of enhanced osteoblastic activities may further be explored ultimately towards future therapeutic use of MSCs.

  14. 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.

  15. 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.

  16. Effective treatment of steroid and therapy-refractory acute graft-versus-host disease with a novel mesenchymal stromal cell product (MSC-FFM).

    Science.gov (United States)

    Bader, Peter; Kuçi, Zyrafete; Bakhtiar, Shahrzad; Basu, Oliver; Bug, Gesine; Dennis, Michael; Greil, Johann; Barta, Aniko; Kállay, Krisztián M; Lang, Peter; Lucchini, Giovanna; Pol, Raj; Schulz, Ansgar; Sykora, Karl-Walter; von Luettichau, Irene; Herter-Sprie, Grit; Uddin, Mohammad Ashab; Jenkin, Phil; Alsultan, Abdulrahman; Buechner, Jochen; Stein, Jerry; Kelemen, Agnes; Jarisch, Andrea; Soerensen, Jan; Salzmann-Manrique, Emilia; Hutter, Martin; Schäfer, Richard; Seifried, Erhard; Klingebiel, Thomas; Bonig, Halvard; Kuçi, Selim

    2018-01-29

    The inability to generate mesenchymal stromal cells (MSCs) of consistent potency likely is responsible for inconsistent clinical outcomes of patients with aGvHD receiving MSC products. We developed a novel MSC manufacturing protocol characterized by high in vitro potency and near-identity of individual doses, referred to as "MSC-Frankfurt am Main (MSC-FFM)". Herein, we report outcomes of the 69 patients who have received MSC-FFM. These were 51 children and 18 adults with refractory aGvHD grade II (4%), III (36%) or IV (59%). Patients were refractory either to frontline therapy (steroids) (29%) or to steroids and 1-5 additional lines of immunosuppressants (71%) were given infusions in four weekly intervals. The day 28 overall response rate was 83%; at the last follow-up, 61% and 25% of patients were in complete or partial remission. The median follow-up was 8.1 months. Six-month estimate for cumulative incidence of non-relapse mortality was 27% (range, 16-38); leukemia relapse mortality was 2% (range, 0-5). This was associated with a superior six-month overall survival (OS) probability rate of 71% (range, 61-83), compared to the outcome of patients not treated with MSC-FFM. This novel product was effective in children and adults, suggesting that MSC-FFM represents a promising therapy for steroid refractory aGvHD.

  17. Differential effects of platelet rich plasma and washed platelets on the proliferation of mouse MSC cells.

    Science.gov (United States)

    Duan, Jianmin; Kuang, Wei; Tan, Jiali; Li, Hongtao; Zhang, Yi; Hirotaka, Kikuchi; Tadashi, Katayama

    2011-04-01

    Multipotent mesenchymal stem cell (MSC) therapies are being tested clinically for a variety of disorders. However, despite the remarkable clinical advancements in this field, most applications still use traditional culture media containing fetal bovine serum. Platelet-rich plasma (PRP) appears as a novel application for tissue engineering and its effect on bone healing is thought to be mainly dependent on the proliferation promoting function, with the molecular mechanisms largely unknown. In this study, mouse osteogenic progenitor mesenchymal stem cells (MSCs) were cultured in PRP or washed platelet (WPLT)-treated wells or in untreated wells, and analyzed on cycloxygenase 2 (COX2) expression (qRT-PCR), cell growth (MTT assay) and cell differentiation (alkaline phosphatase activity). The results showed that PRP and WPLT stimulated cell growth similarly in the first 6 days, together with the steady induction of COX2 and PGE2. 10 μmol/l celecoxib (an inhibitor of COX2) significantly inhibited the pro-proliferation effects. Interestingly, WPLT had stronger effects than PRP in proliferation at the later time points (6-9 days). ALP activity assay and collagen 1a expression revealed PRP had a mild but statistically significant pro-differentiation effect, while no obvious effects observed in WLPT group. In summary, PRP stimulates initial growth of MSCs in a COX2 partially dependent manner and the less obvious osteogenic differentiation promoting effects of WPLT strongly indicates WPLT rather than the PRP should be the optional choice for expanding MSCs in vitro for clinical use.

  18. Nursing MSc theses: a study of an Iranian College of Nursing and Midwifery in two decades (1990-2010).

    Science.gov (United States)

    Motamed-Jahromi, Mohadeseh; Leila Dehghani, Seyedeh

    2014-05-15

    A thesis is an important part of nursing graduate students' education, which is also their first systematic and scientific attempt to learn the ABCs of research. Articles derived from theses are important for the dissemination of science and the improvement of nursing as a field. Therefore, it is the goal of the present research is to analyze the different aspects of nursing MSc theses and the number of published articles derived from them. This was a descriptive research carried out on 145 nursing MSc theses defended in Razi Faculty of Nursing and Midwifery in Kerman between 1990 and 2010. All of the extracted data were put into an Excel file (2007 version) followed by a data analysis. The results of this study were then presented via the use of descriptive statistics and figures. The research findings showed that most of the theses used a descriptive or analytical-descriptive method, and 42% of them had patients as their participants. They were usually delivered on the subject of health care, and only 58 articles were extracted from the whole 145 theses. The process of writing nursing MSc theses and thesis research articles is improving gradually. However, there is a growing need for empirical and semi-empirical research to bridge the gap between theory and practice, which is also a major concern among nurses.

  19. Treatment of radio-induced colorectal lesions with Mesenchymal Stromal Cells (MSC): part of the inflammatory process

    International Nuclear Information System (INIS)

    Bessout, R.

    2012-01-01

    Throughout the last decades, radiotherapy established as a major tool in the treatment of abdomino-pelvic cancers. Despite great technological evolutions, radiotherapy remains associated with side effects that can sometimes be really harmful, this being mainly due to the toxicity of ionizing radiations for healthy tissues surrounding the tumor. As part of abdomino-pelvic radio-therapies, these side effects mainly affect the gastrointestinal tract, which is very sensitive to radiations. The development of curative treatments thus became a priority. Mesenchymal stem cells (MSC) showed their immunomodulatory ability as well as their ability to regenerate tissue in many models. During my thesis, we aimed at giving rise to the therapeutic advantage brought by MSC in the treatment of radioinduced damage as well as the underlying molecular mechanisms. Our results allowed us to demonstrate the efficiency of our treatment with an effect both on the colic epithelial structure and on its contractile functions. We demonstrated that this therapeutical efficiency depends on two processes. Stimulation of the epithelial proliferation through the Wnt pathway allows the epithelial regeneration process to be enhanced. The increased local corticosterone secretion allows the number and the activation state of T lymphocytes to diminish. Our results moreover suggest the existence of a link between the two observed phenomenons thus providing with a new proof of the combinatory effects of MSC therapy. (author)

  20. System Trade-Off Study and Opto-Thermo Analysis of a Sunshield on the MSC of the KOMPSAT-2

    Directory of Open Access Journals (Sweden)

    Young-Soo Kim

    2003-12-01

    Full Text Available The Multi-Spectral Camera (MSC is the payload of KOMPSAT-2 which is designed for earth imaging in optical and near-infrared region on a sun-synchronous orbit. The telescope in the MSC is a Ritchey-Chretien type with large aperture. The telescope structure should be well stabilized and the optical alignment should be kept steady so that best images can be achieved. However, the MSC is exposed to adverse thermal environment on the orbit which can give impacts on optical performance. Solar incidence can bring non-uniform temperature rise on the telescope tube which entails unfavorable thermal distortion. Three ways of preventing the solar radiation were proposed, which were installing external mechanical shield, internal shield, and maneuvering the spacecraft. After trade-off study, internal sun shield was selected as a practical and optimal solution to minimize the effect of the solar radiation. In addition, detailed designs of the structure and sunshield were produced and analyses have been performed. The results were assessed to verify their impacts to the image quality. It was confirmed that the internal sunshield complies with the requirements and would improve image quality.

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

    Science.gov (United States)

    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. PMID:22912639

  2. 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...

  3. Presentation of MSc in Higher Education Dissertation School Meeting : What are the key dimensions of the personal tutor role for nurse education today?,

    OpenAIRE

    Leddington, Susan

    2012-01-01

    Presentation of MSc in Higher Education Dissertation School Meeting : What are the key dimensions of the personal tutor role for nurse education today?, A literature review, Missenden Abbey, June 2009, presentation

  4. A small population of resident limb bud mesenchymal cells express few MSC-associated markers, but the expression of these markers is increased immediately after cell culture.

    Science.gov (United States)

    Marín-Llera, Jessica Cristina; Chimal-Monroy, Jesús

    2018-05-01

    Skeletal progenitors are derived from resident limb bud mesenchymal cells of the vertebrate embryos. However, it remains poorly understood if they represent stem cells, progenitors, or multipotent mesenchymal stromal cells (MSC). Derived-MSC of different adult tissues under in vitro experimental conditions can differentiate into the same cellular lineages that are present in the limb. Here, comparing non-cultured versus cultured mesenchymal limb bud cells, we determined the expression of MSC-associated markers, the in vitro differentiation capacity and their gene expression profile. Results showed that in freshly isolated limb bud mesenchymal cells, the proportion of cells expressing Sca1, CD44, CD105, CD90, and CD73 is very low and a low expression of lineage-specific genes was observed. However, recently seeded limb bud mesenchymal cells acquired Sca1 and CD44 markers and the expression of the key differentiation genes Runx2 and Sox9, while Scx and Pparg genes decreased. Also, their chondrogenic differentiation capacity decreased through cellular passages while the osteogenic increased. Our findings suggest that the modification of the cell adhesion process through the in vitro method changed the limb mesenchymal cell immunophenotype leading to the expression and maintenance of common MSC-associated markers. These findings could have a significant impact on MSC study and isolation strategy because they could explain common variations observed in the MSC immunophenotype in different tissues. © 2018 International Federation for Cell Biology.

  5. 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.

  6. Employability and career experiences of international graduates of MSc Public Health: a mixed methods study.

    Science.gov (United States)

    Buunaaisie, C; Manyara, A M; Annett, H; Bird, E L; Bray, I; Ige, J; Jones, M; Orme, J; Pilkington, P; Evans, D

    2018-05-08

    This article aims to describe the public health career experiences of international graduates of a Master of Science in Public Health (MSc PH) programme and to contribute to developing the evidence base on international public health workforce capacity development. A sequential mixed methods study was conducted between January 2017 and April 2017. Ninety-seven international graduates of one UK university's MSc PH programme were invited to take part in an online survey followed by semistructured interviews, for respondents who consented to be interviewed. We computed the descriptive statistics of the quantitative data obtained, and qualitative data were thematically analysed. The response rate was 48.5%. Most respondents (63%) were employed by various agencies within 1 year after graduation. Others (15%) were at different stages of doctor of philosophy studies. Respondents reported enhanced roles after graduation in areas such as public health policy analysis (74%); planning, implementation and evaluation of public health interventions (74%); leadership roles (72%); and research (70%). The common perceived skills that were relevant to the respondents' present jobs were critical analysis (87%), multidisciplinary thinking (86%), demonstrating public health leadership skills (84%) and research (77%). Almost all respondents (90%) were confident in conducting research. Respondents recommended the provision of longer public health placement opportunities, elective courses on project management and advanced statistics, and 'internationalisation' of the programme's curriculum. The study has revealed the relevance of higher education in public health in developing the career prospects and skills of graduates. International graduates of this MSc PH programme were satisfied with the relevance and impact of the skills they acquired during their studies. The outcomes of this study can be used for curriculum reformation. Employers' perspectives of the capabilities of these

  7. Stress-Strain state of structural elements of LWR fuel rods modeling in the MSC.MARC and ANSYS software

    International Nuclear Information System (INIS)

    Kuznetsov, A.; Kuznetsov, V.; Krupkin, A.; Kashirin, B.; Medvedev, A.; Novikov, V.

    2009-01-01

    The results of stress-strain state in the fuel rod spring fixing lock coils modeling are presented in this paper. The solution of this problem was realized in finite-element software MSC.MARC and ANSIS. The solution was obtained in the three-dimensional setting, taking into account multicontact interaction and all physical and geometric nonlinearities. The finite-element models were verified on analytical parities and experimental data. Results of verification have proved a correctness of the accepted finite-element models

  8. [Study of building quantitative analysis model for chlorophyll in winter wheat with reflective spectrum using MSC-ANN algorithm].

    Science.gov (United States)

    Liang, Xue; Ji, Hai-yan; Wang, Peng-xin; Rao, Zhen-hong; Shen, Bing-hui

    2010-01-01

    Preprocess method of multiplicative scatter correction (MSC) was used to reject noises in the original spectra produced by the environmental physical factor effectively, then the principal components of near-infrared spectroscopy were calculated by nonlinear iterative partial least squares (NIPALS) before building the back propagation artificial neural networks method (BP-ANN), and the numbers of principal components were calculated by the method of cross validation. The calculated principal components were used as the inputs of the artificial neural networks model, and the artificial neural networks model was used to find the relation between chlorophyll in winter wheat and reflective spectrum, which can predict the content of chlorophyll in winter wheat. The correlation coefficient (r) of calibration set was 0.9604, while the standard deviation (SD) and relative standard deviation (RSD) was 0.187 and 5.18% respectively. The correlation coefficient (r) of predicted set was 0.9600, and the standard deviation (SD) and relative standard deviation (RSD) was 0.145 and 4.21% respectively. It means that the MSC-ANN algorithm can reject noises in the original spectra produced by the environmental physical factor effectively and set up an exact model to predict the contents of chlorophyll in living leaves veraciously to replace the classical method and meet the needs of fast analysis of agricultural products.

  9. Changing strategy and implementation of a new treatment protocol for cleft palate surgery in "Maria Sklodowska Curie" (MSC) Children's Hospital, Bucharest, Romania.

    Science.gov (United States)

    Spataru, Radu; Mark, Hans

    2014-12-01

    In "Maria Sklodowska Curie" (MSC) Children's Hospital, Bucharest, Romania, cleft palate repair has been performed according to von Langenbeck since 1984. The speech was good in most patients but wide clefts had a high percentage of fistulas, abnormal speech due to short length and limited mobility of the soft palate. In 2009, the protocol was changed to Gothenburg Delayed Hard Palate Closure, (DHPC) technique. The present evaluation was performed to study the implementation of this technique. One hundred and sixty-eight patients with cleft palate were admitted, 89 isolated cleft palate (ICP), 53 unilateral (UCLP) and 26 bilateral (BCLP). In these, 228 surgical interventions were performed. Soft Palate Repair (SPR) and Hard Palate Repair (HPR) were performed with the DHPC procedure. The transfer to this technique was successfully performed in three steps: one team visit to Gothenburg by a surgeon from MSC and two visits by surgeons from Gothenburg to the MSC. Patients with SPR and HPR were operated on without major complications and there were no differences in results between Gothenburg surgeons and MSC surgeons. The interventions with SPR and HPR technique were proven to be easy to teach and learn and successfully performed without major complications. For cleft patients at MSC hospital it has meant earlier surgery, less re-operations and complications. This report shows a successful change of strategy for palatal repair with improved outcome regarding surgery. In future, speech and growth will be followed on a regular basis and will be compared with results from the Gothenburg Cleft Team.

  10. INFUSION OF THIRD-PARTY MESENCHYMAL STEM CELLS (MSC) AFTER KIDNEY AND LIVER TRANSPLANTATION: A PHASE I-II, OPEN-LABEL, CLINICAL STUDY (EudraCT 2011-001822-81 & NCT01429038)

    OpenAIRE

    DETRY, Olivier; DELBOUILLE, Marie-Hélène; LECHANTEUR, Chantal; SOMJA, Joan; DE ROOVER, Arnaud; WEEKERS, Laurent; SQUIFFLET, Jean-Paul; Honoré, Pierre; DELVENNE, Philippe; MEURISSE, Michel; BAUDOUX, Etienne; BEGUIN, Yves

    2013-01-01

    MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC infusion after cadaveric kidney and liver transplantation in a prospective phase I-II study, taking advantage of our centre expertise and experience in MSC use in graft-versus-host disease (GVHD) after bone marrow transplantation and using an already functioning GMP-compliant laboratory producing...

  11. Effect of mesenchymal stromal cells (MSC) on chronic visceral hypersensitivity in a radio-induced colonic ulceration model in the rat

    International Nuclear Information System (INIS)

    Durand, Christelle

    2014-01-01

    Patients who undergo pelvic radiotherapy may develop significant incidence of undesirable chronic gastrointestinal complications resulting from radiation-induced damages around the tumour. Chronic visceral pain is one of the radiation-induced side effects that greatly affects the quality of life of 'cancer survivors'. The lack of effective analgesic treatment highlights the importance of novel and effective therapeutic strategies. In our laboratory, mesenchymal stromal cell (MSC) based approach showed beneficial immunomodulatory and regenerative effects in a rat model of irreversible radiationinduced colonic ulcers. The goal of my work was to assess the relevance of this model to study radiation-induced visceral persistent hypersensitivity and its modulation by MSC treatment. We first demonstrated that this model is associated with long-lasting visceral hypersensitivity and central neuronal sensitization. In this context we showed then that mast cells (MC) are involved in the mechanism of peripheral sensitization. Moreover, we suggested the implication of the neuro-mediator NO . in the pathophysiology of persistent radiation-induced visceral hypersensitivity. We also suggested that MSC treatment reversed radiation-induced hypersensitivity by a mechanism that in part may involve the modulation of MC activation and/or the decrease in the number of MC and nerve fiber interactions. In addition, MSC treatment reduced the percentage of nitrinergic neurons, increased after irradiation, and restored colonic muscular contractibility. Such processes may promote the therapeutic benefit of MSC observed in our study. In conclusion, this work provided new insights on the therapeutic benefit of MSC in our study model and a new argument in favour of their use in a future clinical trial to cure abdomino-pelvic radiotherapy side effects. (author) [fr

  12. Input Files and Procedures for Analysis of SMA Hybrid Composite Beams 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 alloys (SMAs) and SMA hybrid composites (SMAHCs) was recently implemented in the commercial codes MSC.Nastran and ABAQUS. The model is implemented and supported within the core of the commercial codes, so no user subroutines or external calculations are necessary. The model and resulting structural analysis has been previously demonstrated and experimentally verified for thermoelastic, vibration and acoustic, and structural shape control applications. The commercial implementations are described in related documents cited in the references, where various results are also shown that validate the commercial implementations relative to a research code. This paper is a companion to those documents in that it provides additional detail on the actual input files and solution procedures and serves as a repository for ASCII text versions of the input files necessary for duplication of the available results.

  13. CRANK-PISTON MODEL OF INTERNAL COMBUSTION ENGINE USING CAD/CAM/CAE IN THE MSC ADAMS

    Directory of Open Access Journals (Sweden)

    Michał BIAŁY

    2017-03-01

    Full Text Available The article presents the modeling and simulation of the crank-piston model of internal combustion engine. The object of the research was the engine of the vehicle from the B segment. The individual elements of the gasoline engine were digitizing using the process of reverse engineering. After converting the geometry, assembling was imported to MSC Adams software. The crank-piston system was specified by boundary conditions of piston forces applied on the pistons crowns. This force was obtain from the cylinder pressure recorded during the tests, that were carried out on a chassis dynamometer. The simulation studies allowed t determine the load distribution in a dynamic state for the selected kinematic pairs.

  14. 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.

  15. Education of 'nuclear' students (BSc and MSc curricula) at the Faculty of Nuclear Science and Physical Engineering, Czech Technical University in Prague

    International Nuclear Information System (INIS)

    Matejka, K.; Zeman, J.

    2003-01-01

    The Faculty of Nuclear Science and Physical Engineering, Czech Technical University in Prague has been educating nuclear power engineering experts for nearly half a century. The article describes the current status and prospects of education of new specialists at the faculty for all nuclear power-related areas within the MSc and BSc level curricula. The current transition to 'European type' structured education, enabling students who have graduated from the BSc programme to continue smoothly their MSc programme, is outlined. The major courses of the 'Nuclear Engineering' educational specialisation, focused on nuclear power, environment, and dosimetry, are highlighted, including the number of lessons taught in each study year. (author)

  16. Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study.

    Science.gov (United States)

    Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

    2013-04-11

    Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. MSCs were derived from negative HLA cross-match donors. Donor bone marrow was harvested 5 weeks prior to KT. At the time of transplantation, 1 x 106 cell/kg of donor MSC was directly injected into the bone marrow of the recipient's right iliac bone. Patients' clinical outcomes, presence of mixed chimerism by short tandem repeat polymerase chain reaction, analysis of plasma FoxP3 mRNA and cytokine level, and mixed lymphocyte reaction (MLR) were performed. Seven patients enrolled in this study and received donor MSC injections simultaneously with LDKT. The median age of recipients was 36 years (32 ~ 48). The number of HLA mismatches was 3 or less in 5 and more than 3 in 2. No local complications or adverse events such as hypersensitivity occurred during or after the injection of donor MSC. There was no graft failure, but the biopsy-proven acute rejections were observed in 3 recipients during the follow-up period controlled well with steroid pulse therapy (SPT). The last serum creatinine was a median of 1.23 mg/dL (0.83 ~ 2.07). Mixed chimerism was not detected in the peripheral blood of the recipients at 1 and 8 week of post-transplantation. Donor-specific lymphocyte or T cell proliferation and Treg priming responses were observed in some patients. Plasma level of IL-10, a known mediator of MSC-induced immune suppression, increased in the patients with Treg induction. Donor MSC injection into the iliac bone at the time of KT was feasible and safe. A possible correlation was observed between the induction of inhibitory

  17. University-Industry Teaching Collaborations: A Case Study of the MSc in Structural Integrity Co-Produced by Brunel University London and The Welding Institute

    Science.gov (United States)

    Samuel, Gabrielle; Donovan, Claire; Lee, Jeung

    2018-01-01

    The paper presents an evaluation of an MSc in Structural Integrity co-produced by Brunel University London and industry partner The Welding Institute (TWI), designed to supply 'work-ready' graduates. Pre-, mid- and post-course quantitative surveys were administered to students, and two mid-term focus groups were conducted. Pre- and post-course…

  18. Silk-ionomer and silk-tropoelastin hydrogels as charged three-dimensional culture platforms for the regulation of hMSC response.

    Science.gov (United States)

    Calabrese, Rossella; Raia, Nicole; Huang, Wenwen; Ghezzi, Chiara E; Simon, Marc; Staii, Cristian; Weiss, Anthony S; Kaplan, David L

    2017-09-01

    The response of human bone marrow-derived mesenchymal stem cells (hMSCs) encapsulated in three-dimensional (3D) charged protein hydrogels was studied. Combining silk fibroin (S) with recombinant human tropoelastin (E) or silk ionomers (I) provided protein composite alloys with tunable physicochemical and biological features for regulating the bioactivity of encapsulated hMSCs. The effects of the biomaterial charges on hMSC viability, proliferation and chondrogenic or osteogenic differentiation were assessed. The silk-tropoelastin or silk-ionomers hydrogels supported hMSC viability, proliferation and differentiation. Gene expression of markers for chondrogenesis and osteogenesis, as well as biochemical and histological analysis, showed that hydrogels with different S/E and S/I ratios had different effects on cell fate. The negatively charged hydrogels upregulated hMSC chondrogenesis or osteogenesis, with or without specific differentiation media, and hydrogels with higher tropoelastin content inhibited the differentiation potential even in the presence of the differentiation media. The results provide insight on charge-tunable features of protein-based biomaterials to control hMSC differentiation in 3D hydrogels, as well as providing a new set of hydrogels for the compatible encapsulation and utility for cell functions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Use of most significant change (MSC) technique to evaluate health promotion training of maternal community health workers in Cianjur district, Indonesia.

    Science.gov (United States)

    Limato, Ralalicia; Ahmed, Rukhsana; Magdalena, Amelia; Nasir, Sudirman; Kotvojs, Fiona

    2018-02-01

    Maternal health promotion is a defined activity in the community integrated posts (Posyandu) in Indonesia. However, it is often neglected due to limited knowledge and skills of the community health workers (kader). We conducted health promotion training for the kader and village midwives in four villages in Cianjur district. This study describes the use of "most significant change" (MSC) technique to evaluate impact of health promotion to the beneficiaries and community at large. The MSC uses stories as raw data. Through interviews focused on perception of change, stories were collected from four pregnant women, eight kader and three village midwives. A Panel consisting of policy and programme managers and implementers read all the stories. The story by a pregnant woman who routinely attended Posyandu was selected as the story with most significant change. Her story highlighted changes in kader's knowledge and communication of health messages and attitude towards pregnant women. She expressed these changes impacted community awareness about health and to seek help from kader.The MSC technique enabled stakeholders to view raw data and evaluate the impact of health promotion from the beneficiary's perspective. At the same time, recipients of health promotion contributed to the decision process of evaluation through their stories. The different perspectives on the MSC reflected individual's objectives of the health promotion. The application of this technique is limited in maternal health promotion programme in Indonesia, and none have been published in peer reviewed journals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. 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.

  1. 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.

  2. A co-culture system with three different primary human cell populations reveals that biomaterials and MSC modulate macrophage-driven fibroblast recruitment.

    Science.gov (United States)

    Caires, Hugo R; Barros da Silva, Patrícia; Barbosa, Mário A; Almeida, Catarina R

    2018-03-01

    The biological response to implanted biomaterials is a complex and highly coordinated phenomenon involving many different cell types that interact within 3D microenvironments. Here, we increased the complexity of a 3D platform to include at least 3 cell types that play a role in the host response upon scaffold implantation. With this system, it was possible to address how immune responses triggered by 3D biomaterials mediate recruitment of stromal cells that promote tissue regeneration, mesenchymal stromal/stem cells (MSC), or a foreign body response, fibroblasts. Primary human macrophages yielded the highest fibroblast recruitment when interacting with chitosan scaffolds but not polylactic acid. Interestingly, when there were MSC and fibroblasts in the same environment, macrophages in chitosan scaffolds again promoted a significant increase on fibroblast recruitment, but not of MSC. However, macrophages that were firstly allowed to interact with MSC within the scaffolds were no longer able to recruit fibroblasts. This study illustrates the potential to use different scaffolds to regulate the dynamics of recruitment of proregenerative or fibrotic cell types through immunomodulation. Overall, this work strengths the idea that ex vivo predictive systems need to consider the different players involved in the biological response to biomaterials and that timing of arrival of specific cell types will affect the outcome. Copyright © 2017 John Wiley & Sons, Ltd.

  3. One-step derivation of mesenchymal stem cell (MSC-like cells from human pluripotent stem cells on a fibrillar collagen coating.

    Directory of Open Access Journals (Sweden)

    Yongxing Liu

    Full Text Available Controlled differentiation of human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs into cells that resemble adult mesenchymal stem cells (MSCs is an attractive approach to obtain a readily available source of progenitor cells for tissue engineering. The present study reports a new method to rapidly derive MSC-like cells from hESCs and hiPSCs, in one step, based on culturing the cells on thin, fibrillar, type I collagen coatings that mimic the structure of physiological collagen. Human H9 ESCs and HDFa-YK26 iPSCs were singly dissociated in the presence of ROCK inhibitor Y-27632, plated onto fibrillar collagen coated plates and cultured in alpha minimum essential medium (alpha-MEM supplemented with 10% fetal bovine serum, 50 uM magnesium L-ascorbic acid phosphate and 100 nM dexamethasone. While fewer cells attached on the collagen surface initially than standard tissue culture plastic, after culturing for 10 days, resilient colonies of homogenous spindle-shaped cells were obtained. Flow cytometric analysis showed that a high percentage of the derived cells expressed typical MSC surface markers including CD73, CD90, CD105, CD146 and CD166 and were negative as expected for hematopoietic markers CD34 and CD45. The MSC-like cells derived from pluripotent cells were successfully differentiated in vitro into three different lineages: osteogenic, chondrogenic, and adipogenic. Both H9 hES and YK26 iPS cells displayed similar morphological changes during the derivation process and yielded MSC-like cells with similar properties. In conclusion, this study demonstrates that bioimimetic, fibrillar, type I collagen coatings applied to cell culture plates can be used to guide a rapid, efficient derivation of MSC-like cells from both human ES and iPS cells.

  4. 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.

  5. PLA-poloxamer/poloxamine copolymers for ligament tissue engineering: sound macromolecular design for degradable scaffolds and MSC differentiation.

    Science.gov (United States)

    Leroy, Adrien; Nottelet, Benjamin; Bony, Claire; Pinese, Coline; Charlot, Benoît; Garric, Xavier; Noël, Danièle; Coudane, Jean

    2015-04-01

    The treatment of anterior cruciate ligament (ACL) failures remains a current clinical challenge. The present study aims at providing suitable degradable scaffolds for ligament tissue engineering. First, we focus on the design and the evaluation of poly(lactide)/poloxamer or poly(lactide)/poloxamine multiblock copolymers selected and developed to have suitable degradation and mechanical properties to match ACL repair. In the second part, it is shown that the copolymers can be processed in the form of microfibers and scaffolds consisting of a combination of twisted/braided fibers to further modulate the mechanical properties and prepare scaffold prototypes suitable for ligament application. Finally, after assessment of their cytocompatibility, the polymer scaffolds are associated with mesenchymal stem cells (MSCs). MSC differentiation toward a ligament fibroblast phenotype is promoted by a dual stimulation including an inductive culture medium and cyclic mechanical loads. RT-qPCR analyses confirm the potential of our scaffolds and MSCs for ACL regeneration with upregulation of some differentiation markers including Scleraxis, Tenascin-C and Tenomodulin.

  6. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Homologous structure-function relationships between native fibrocartilage and tissue engineered from MSC-seeded nanofibrous scaffolds.

    Science.gov (United States)

    Nerurkar, Nandan L; Han, Woojin; Mauck, Robert L; Elliott, Dawn M

    2011-01-01

    Understanding the interplay of composition, organization and mechanical function in load-bearing tissues is a prerequisite in the successful engineering of tissues to replace diseased ones. Mesenchymal stem cells (MSCs) seeded on electrospun scaffolds have been successfully used to generate organized tissues that mimic fibrocartilages such as the knee meniscus and the annulus fibrosus of the intervertebral disc. While matrix deposition has been observed in parallel with improved mechanical properties, how composition, organization, and mechanical function are related is not known. Moreover, how this relationship compares to that of native fibrocartilage is unclear. Therefore, in the present work, functional fibrocartilage constructs were formed from MSC-seeded nanofibrous scaffolds, and the roles of collagen and glycosaminoglycan (GAG) in compressive and tensile properties were determined. MSCs deposited abundant collagen and GAG over 120 days of culture, and these extracellular molecules were organized in such a way that they performed similar mechanical functions to their native roles: collagen dominated the tensile response while GAG was important for compressive properties. GAG removal resulted in significant stiffening in tension. A similar stiffening response was observed when GAG was removed from native inner annulus fibrosus, suggesting an interaction between collagen fibers and their surrounding extrafibrillar matrix that is shared by both engineered and native fibrocartilages. These findings strongly support the use of electrospun scaffolds and MSCs for fibrocartilage tissue engineering, and provide insight on the structure-function relations of both engineered and native biomaterials. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Structural study of the membrane protein MscL using cell-free expression and solid-state NMR

    Science.gov (United States)

    Abdine, Alaa; Verhoeven, Michiel A.; Park, Kyu-Ho; Ghazi, Alexandre; Guittet, Eric; Berrier, Catherine; Van Heijenoort, Carine; Warschawski, Dror E.

    2010-05-01

    High-resolution structures of membrane proteins have so far been obtained mostly by X-ray crystallography, on samples where the protein is surrounded by detergent. Recent developments of solid-state NMR have opened the way to a new approach for the study of integral membrane proteins inside a membrane. At the same time, the extension of cell-free expression to the production of membrane proteins allows for the production of proteins tailor made for NMR. We present here an in situ solid-state NMR study of a membrane protein selectively labeled through the use of cell-free expression. The sample consists of MscL (mechano-sensitive channel of large conductance), a 75 kDa pentameric α-helical ion channel from Escherichia coli, reconstituted in a hydrated lipid bilayer. Compared to a uniformly labeled protein sample, the spectral crowding is greatly reduced in the cell-free expressed protein sample. This approach may be a decisive step required for spectral assignment and structure determination of membrane proteins by solid-state NMR.

  9. Belay Tessema, MSc

    African Journals Online (AJOL)

    prenatal behavior. The study focused on ... have a wide appeal to policy makers,. Source of data for ... homogeneity in prenatal care behavior ..... to adopt what may be a major change in life style to ... particularly if not within marriage for fear.

  10. CZCSL3MSC

    Data.gov (United States)

    National Aeronautics and Space Administration — The Coastal Zone Color Scanner Experiment (CZCS) was the first instrument devoted to the measurement of ocean color and flown on a spacecraft. Although other...

  11. 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.

  12. The influence of specific binding of collagen-silk chimeras to silk biomaterials on hMSC behavior.

    Science.gov (United States)

    An, Bo; DesRochers, Teresa M; Qin, Guokui; Xia, Xiaoxia; Thiagarajan, Geetha; Brodsky, Barbara; Kaplan, David L

    2013-01-01

    Collagen-like proteins in the bacteria Streptococcus pyogenes adopt a triple-helix structure with a thermal stability similar to that of animal collagens, can be expressed in high yield in Escherichia coli and can be easily modified through molecular biology techniques. However, potential applications for such recombinant collagens are limited by their lack of higher order structure to achieve the physical properties needed for most biomaterials. To overcome this problem, the S. pyogenes collagen domain was fused to a repetitive Bombyx mori silk consensus sequence, as a strategy to direct specific non-covalent binding onto solid silk materials whose superior stability, mechanical and material properties have been previously established. This approach resulted in the successful binding of these new collagen-silk chimeric proteins to silk films and porous scaffolds, and the binding affinity could be controlled by varying the number of repeats in the silk sequence. To explore the potential of collagen-silk chimera for regulating biological activity, integrin (Int) and fibronectin (Fn) binding sequences from mammalian collagens were introduced into the bacterial collagen domain. The attachment of bioactive collagen-silk chimeras to solid silk biomaterials promoted hMSC spreading and proliferation substantially in comparison to the controls. The ability to combine the biomaterial features of silk with the biological activities of collagen allowed more rapid cell interactions with silk-based biomaterials, improved regulation of stem cell growth and differentiation, as well as the formation of artificial extracellular matrices useful for tissue engineering applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Partial Purification and Characterization of a Heat Stable α-Amylase from a Thermophilic Actinobacteria, Streptomyces sp. MSC702.

    Science.gov (United States)

    Singh, Renu; Kumar, Vijay; Kapoor, Vishal

    2014-01-01

    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(+), Co(2+), and Mo(2+), whereas Pb(2+), Mn(2+), Mg(2+), Cu(2+), Zn(2+), Ba(2+), Ca(2+), Hg(2+), Sn(2+), Cr(3+), Al(3+), Ag(+), and Fe(2+) 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 K m of 2.4 mg/mL and V max of 21853.0 μmol/min/mg for soluble potato starch. The results indicate that the enzyme reflects their potentiality towards industrial utilization.

  14. Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study

    OpenAIRE

    Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

    2013-01-01

    Background Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. Methods MSCs were derived from negative ...

  15. Identification of a subpopulation of marrow MSC-derived medullary adipocytes that express osteoclast-regulating molecules: marrow adipocytes express osteoclast mediators.

    Directory of Open Access Journals (Sweden)

    Vance Holt

    Full Text Available Increased marrow medullary adipogenesis and an associated decrease in bone mineral density, usually observed in elderly individuals, is a common characteristic in senile osteoporosis. In this study we investigated whether cells of the medullary adipocyte lineage have the potential to directly support the formation of osteoclasts, whose activity in bone leads to bone degradation. An in vitro mesenchymal stem cell (MSC-derived medullary adipocyte lineage culture model was used to study the expression of the important osteoclast mediators RANKL, M-CSF, SDF-1, and OPG. We further assessed whether adipocytes at a specific developmental stage were capable of supporting osteoclast-like cell formation in culture. In vitro MSC-derived medullary adipocytes showed an mRNA and protein expression profile of M-CSF, RANKL, and OPG that was dependent on its developmental/metabolic stage. Furthermore, RANKL expression was observed in MSC-derived adipocytes that were at a distinct lineage stage and these cells were also capable of supporting osteoclast-like cell formation in co-cultures with peripheral blood mononuclear cells. These results suggest a connection between medullary adipocytes and osteoclast formation in vivo and may have major significance in regards to the mechanisms of decreased bone density in senile osteoporosis.

  16. 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.

  17. Changes in SeMSC, glucosinolates and sulforaphane levels, and in proteome profile in broccoli (Brassica oleracea var. Italica) fertilized with sodium selenate.

    Science.gov (United States)

    Sepúlveda, Ignacio; Barrientos, Herna; Mahn, Andrea; Moenne, Alejandra

    2013-05-07

    The aim of this work was to analyze the effect of sodium selenate fortification on the content of selenomethyl selenocysteine (SeMSC), total glucosinolates and sulforaphane, as well as the changes in protein profile of the inflorescences of broccoli (Brassica oleracea var. Italica). Two experimental groups were considered: plants treated with 100 μmol/L sodium selenate (final concentration in the pot) and control plants treated with water. Fortification began 2 weeks after transplantation and was repeated once a week during 10 weeks. Broccoli florets were harvested when they reached appropriate size. SeMSC content in broccoli florets increased significantly with sodium selenate fortification; but total glucosinolates and sulforaphane content as well as myrosinase activity were not affected. The protein profile of broccoli florets changed due to fortification with sodium selenate. Some proteins involved in general stress-responses were up-regulated, whereas down-regulated proteins were identified as proteins involved in protection against pathogens. This is the first attempt to evaluate the physiological effect of fortification with sodium selenate on broccoli at protein level. The results of this work will contribute to better understanding the metabolic processes related with selenium uptake and accumulation in broccoli.

  18. Changes in SeMSC, Glucosinolates and Sulforaphane Levels, and in Proteome Profile in Broccoli (Brassica oleracea var. Italica Fertilized with Sodium Selenate

    Directory of Open Access Journals (Sweden)

    Alejandra Moenne

    2013-05-01

    Full Text Available The aim of this work was to analyze the effect of sodium selenate fortification on the content of selenomethyl selenocysteine (SeMSC, total glucosinolates and sulforaphane, as well as the changes in protein profile of the inflorescences of broccoli (Brassica oleracea var. Italica. Two experimental groups were considered: plants treated with 100 mmol/L sodium selenate (final concentration in the pot and control plants treated with water. Fortification began 2 weeks after transplantation and was repeated once a week during 10 weeks. Broccoli florets were harvested when they reached appropriate size. SeMSC content in broccoli florets increased significantly with sodium selenate fortification; but total glucosinolates and sulforaphane content as well as myrosinase activity were not affected. The protein profile of broccoli florets changed due to fortification with sodium selenate. Some proteins involved in general stress-responses were up-regulated, whereas down-regulated proteins were identified as proteins involved in protection against pathogens. This is the first attempt to evaluate the physiological effect of fortification with sodium selenate on broccoli at protein level. The results of this work will contribute to better understanding the metabolic processes related with selenium uptake and accumulation in broccoli.

  19. Messinian post-evaporitic paleogeography of the Po Plain-Adriatic region by 3D numerical modeling: implications for the Central Mediterranean desiccation during the MSC

    Science.gov (United States)

    Amadori, Chiara; Garcia-Castellanos, Daniel; Di Giulio, Andrea; Fantoni, Roberto; Ghielmi, Manlio; Sternai, Pietro; Toscani, Giovanni

    2017-04-01

    In the last decades the Messinian Salinity Crisis (MSC) has been the topic of a number of studies, in particular in onshore areas, as they offer a unique opportunity to analyze the controlling factors and the geological consequences of the estimated 1.5 km sea-level drop. During the MSC, the geometry of western and eastern sides of the Mediterranean basin was similar to the present day basin while, important changes took place in the central portion as a consequence of the (still ongoing) tectonic activity of the Apennine domain. Recent high-resolution 2D seismo-stratigraphic and 1D backstripping analysis by Eni E&P group described a step-wise sea-level lowering during evaporitic and post-evaporitic MSC phases in the Po Plain-Northern Adriatic foreland (PPAF), with a sea-level drop not exceeding 900 m. Thanks to a dense grid of 2D seismic profiles, integrated with ca. 200 well logs (confidential data, courtesy of ENI E&P), a 3D reconstruction of the entire northern PPAF basin geometry and the facies distribution during the Latest Messinian time has been carried out. In this study, we performed a 3D backstripping and lithospheric scale uplift calculations of the northern PPAF basin testing the 800-900m of sea-level draw down. The resulted restored Latest Messinian paleotopography (corresponding to the bottom Pliocene in the most of the study area) and related shoreline position, strongly fit with the recentmost continental/marine facies distribution maps. The latest Messinian morphology shows deep marine basins persisting during the entire MSC period, filled by clastic turbiditic sediments and a wide emerged area along the Southern Alps margin and Friulian-Venetian basin. A 3D reconstruction of the Latest Messinian surface shows peculiar river incisions along the Southern Alps margin; these V-shape canyons perfectly fit with the present day fluvial network, dating back the drainage origin at least at the Messinian acme. Moreover, if in a well-constrained marginal

  20. The Schizosaccharomyces pombe JmjC-protein, Msc1, prevents H2A.Z localization in centromeric and subtelomeric chromatin domains.

    Directory of Open Access Journals (Sweden)

    Luke Buchanan

    2009-11-01

    Full Text Available Eukaryotic genomes are repetitively packaged into chromatin by nucleosomes, however they are regulated by the differences between nucleosomes, which establish various chromatin states. Local chromatin cues direct the inheritance and propagation of chromatin status via self-reinforcing epigenetic mechanisms. Replication-independent histone exchange could potentially perturb chromatin status if histone exchange chaperones, such as Swr1C, loaded histone variants into wrong sites. Here we show that in Schizosaccharomyces pombe, like Saccharomyces cerevisiae, Swr1C is required for loading H2A.Z into specific sites, including the promoters of lowly expressed genes. However S. pombe Swr1C has an extra subunit, Msc1, which is a JumonjiC-domain protein of the Lid/Jarid1 family. Deletion of Msc1 did not disrupt the S. pombe Swr1C or its ability to bind and load H2A.Z into euchromatin, however H2A.Z was ectopically found in the inner centromere and in subtelomeric chromatin. Normally this subtelomeric region not only lacks H2A.Z but also shows uniformly lower levels of H3K4me2, H4K5, and K12 acetylation than euchromatin and disproportionately contains the most lowly expressed genes during vegetative growth, including many meiotic-specific genes. Genes within and adjacent to subtelomeric chromatin become overexpressed in the absence of either Msc1, Swr1, or paradoxically H2A.Z itself. We also show that H2A.Z is N-terminally acetylated before, and lysine acetylated after, loading into chromatin and that it physically associates with the Nap1 histone chaperone. However, we find a negative correlation between the genomic distributions of H2A.Z and Nap1/Hrp1/Hrp3, suggesting that the Nap1 chaperones remove H2A.Z from chromatin. These data describe H2A.Z action in S. pombe and identify a new mode of chromatin surveillance and maintenance based on negative regulation of histone variant misincorporation.

  1. Preliminary Analysis of the Social and Scientific Impact of the UAEM-ININ M.Sc. and D.Sc. Graduate Programme in Medical Physics

    Science.gov (United States)

    Mitsoura, Eleni; Isaac-Olive, Keila; Torres-Garcia, Eugenio; Camacho-Lopez, Miguel Angel; Hardy-Perez, Alberto

    2010-12-01

    Sponsored by the International Atomic Energy Agency (IAEA) in 1994, the Instituto Nacional de Investigaciones Nucleares (ININ) started in Mexico a teaching and training programme (Diplomado) in Radiotherapy Medical Physics. Based on this experience, the Universidad Autónoma del Estado de México (UAEM) and the Instituto Nacional de Investigaciones Nucleares (ININ) launched two years later, the first Graduate Programme in Science (M.Sc. and D.Sc.), specialised in Medical Physics in Mexico. A preliminary analysis of the social and scientific impact of the UAEM-ININ Programme is presented in this work based on the achievements attained, regarding the number of graduated Medical Physicists, their geographic and academic origin, their current professional activities and the number of scientific publications produced as a result of the thesis, as well as their citations.

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

    International Nuclear Information System (INIS)

    Singh, Satish S.; Roy, Abhijit; Lee, Boeun; Kumta, Prashant N.

    2016-01-01

    Biphasic mixtures of either Mg"2"+ or combined Mg"2"+ and Sr"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"2"+, Sr"2"+, and PO_4"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"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"2"+ and Sr"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.

  3. 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.

  4. Tefera Belachew', MD, MSc, DLSHTM, Tilahun Yemane, MD, MSc

    African Journals Online (AJOL)

    Dietary quality was assessed by asking the consumption of the major food groups. (cereals-legumes, fruits .... different food groups, their cost and values given to them by the society in ..... Guide to Daily Food Choices. Home and Garden.

  5. The Theoretical, Methodological, and Practical Background for Looking at International Students' Learning Styles, Backgrounds, and Quality Perceptions with Regard to ASB's Three English-Language M.Sc. Programs

    DEFF Research Database (Denmark)

    Skaates, Maria Anne

    This paper looking at the methodological background for a questionnaire study of student perceptions with regard to own learning styles and backgrounds as well as the quality of education in Aarhus School of Business' 3 English-language M.Sc. programs (FIB, EU, and BPM). Theories and models about...... the internationalization of business schools, service quality, and student learning styles are discussed in the paper, as is the statistic methodology for treating the questionnaire responses of the respondents.......This paper looking at the methodological background for a questionnaire study of student perceptions with regard to own learning styles and backgrounds as well as the quality of education in Aarhus School of Business' 3 English-language M.Sc. programs (FIB, EU, and BPM). Theories and models about...

  6. Community Eye Health MSc dissertations

    Directory of Open Access Journals (Sweden)

    Osman L

    2008-12-01

    Full Text Available The seven Exchange articles that follow are based on the dissertations of students at the International Centre for Eye Health, London School of Hygiene and Tropical Medicine, who graduated in 2008.

  7. Degenerate wave and capacitive coupling increase human MSC invasion and proliferation while reducing cytotoxicity in an in vitro wound healing model.

    Directory of Open Access Journals (Sweden)

    Michelle Griffin

    Full Text Available Non-unions pose complications in fracture management that can be treated using electrical stimulation (ES. Bone marrow mesenchymal stem cells (BMMSCs are essential in fracture healing; however, the effect of different clinical ES waveforms on BMMSCs cellular activities remains unknown. We compared the effects of direct current (DC, capacitive coupling (CC, pulsed electromagnetic field (PEMF and degenerate wave (DW on cellular activities including cytotoxicity, proliferation, cell-kinetics and apoptosis by stimulating human-BMMSCs 3 hours a day, up to 5 days. In addition, migration and invasion were assessed using fluorescence microscopy and by quantifying gene and protein expression. We found that DW had the greatest proliferative and least apoptotic and cytotoxic effects compared to other waveforms. DC, DW and CC stimulations resulted in a higher number of cells in S phase and G(2/M phase as shown by cell cycle analysis. CC and DW caused more cells to invade collagen and showed increased MMP-2 and MT1-MMP expression. DC increased cellular migration in a scratch-wound assay and all ES waveforms enhanced expression of migratory genes with DC having the greatest effect. All ES treated cells showed similar progenitor potential as determined by MSC differentiation assay. All above findings were shown to be statistically significant (p<0.05. We conclude that ES can influence BMMSCs activities, especially DW and CC, which show greater invasion and higher cell proliferation compared to other types of ES. Application of DW or CC to the fracture site may help in the recruitment of BMMSCs to the wound that may enhance rate of bone healing at the fracture site.

  8. The Effect of Pulsatile Flow on bMSC-Derived Endothelial-Like Cells in a Small-Sized Artificial Vessel Made by 3-Dimensional Bioprinting

    Directory of Open Access Journals (Sweden)

    Kang Woog Lee

    2018-01-01

    Full Text Available Replacement of small-sized vessels is still challenging. This study is aimed at investigating the possibility of small-sized artificial vessels made by 3-dimensional bioprinting and the effect of pulsatile flow on bMSC-derived endothelial-like cells. Cells were harvested from rabbit bone marrow and primary cultured with or without growth factors. Endothelial differentiation was confirmed by the Matrigel tube formation assay, Western blot, and qRT-PCR. In addition, embedment of endothelial-like cells in an artificial vessel was made by 3-dimensional bioprinting, and the pulsatile flow was performed. For pumped and nonpumped groups, qRT-PCR was performed on CD31 and VE-cadherin gene expression. Endothelial-like cells showed increased gene expression of CD31 and VE-cadherin, and tube formation is observed at each week. Endothelial-like cells grow well in a small-sized artificial vessel made by 3-dimensional bioprinting and even express higher endothelial cell markers when they undergo pulsatile flow condition. Moreover, the pulsatile flow condition gives a positive effect for cell observation not only on the sodium alginate hydrogel layer but also on the luminal surface of the artificial vessel wall. We have developed an artificial vessel, which is a mixture of cells and carriers using a 3-dimensional bioprinting method, and applied pulsatile flow using a peristaltic pump, and we also demonstrated cell growth and differentiation into endothelial cells. This study suggests guidelines regarding a small-sized artificial vessel in the field of tissue engineering.

  9. A stepwise approach for introducing numerical modeling in Environmental Engineering MSc unit: The impact of clear assessment criteria and detailed feedback

    Science.gov (United States)

    Rosolem, R.; Pritchard, J.

    2017-12-01

    An important aspect for the new generation of hydrologists and water resources managers is the understanding of hydrological processes through the application of numerical environmental models. Despite its importance, teaching numerical modeling subjects to young students in our MSc Water and Environment Management programme has been difficult, for instance, due to the wide range of student background and lack or poor contact with numerical modeling tools in the past. In previous years, this numerical skills concept has been introduced as a project assignment in our Terrestrial Hydrometeorology unit. However, previous efforts have shown non-optimal engagement by students with often signs of lack of interest or anxiety. Given our initial experience with this unit, we decided to make substantial changes to the coursework format with the aim to introduce a more efficient learning environment to the students. The proposed changes include: (1) a clear presentation and discussion of the assessment criteria at the beginning of the unit, (2) a stepwise approach in which students use our learning environment to acquire knowledge for individual components of the model step-by-step, and (3) access to timely and detailed feedback allowing for particular steps to be retraced or retested. In order to understand the overall impact on assessment and feedback, we carried out two surveys at the beginning and end of the module. Our results indicate a positive impact to student learning experience, as the students have clearly benefited from the early discussion on assignment criteria and appeared to have correctly identified the skills and knowledge required to carry out the assignment. In addition, we have observed a substantial increase in the quality of the reports. Our results results support that student engagement has increased since changes to the format of the coursework were introduced. Interestingly, we also observed a positive impact on the assignment to the final exam

  10. Janis Huston Audin, MSc, DVM,1950-2009. Dynamic editor-in-chief of the Journal of the American Veterinary Medical Association and strong One Health advocate dies

    Directory of Open Access Journals (Sweden)

    Bruce Kaplan, DVM

    2009-09-01

    Full Text Available Dr Janis H. Audin (MSc Illinois 1975, DVM Illinois 1979, a champion of progressive veterinary medical journalism and ‘One Health’ died on 22 April 2009 following a long, courageous and difficult battle with pancreatic cancer. The world has lost a truly significant One Health leader and advocate. Under her guidance, the Journal of the American Veterinary Medical Association (JAVMA implemented a ‘one-health wonders’ column that recognised and highlighted prominent One Health individuals among the medical and veterinary medical professions in the United States. The American Veterinary Medical Association (AVMA has lost a dedicated and gifted editor-in-chief.Dr Audin joined the editorial staff of the AVMA in 1985, as an assistant editor and was promoted to associate editor in 1989 and editor in 1994. She became the editor-in-chief of both the JAVMA and the American Journal of Veterinary Research in 1995. Prior to that, Dr Audin practised as an associate veterinarian in Calumet City, Illinois, for four years.During her tenure, Dr Audin was noted for implementing procedural and technological changes in the journal to reduce costs, improve timeliness of publications and promote readership interest and awareness. New features in the News section introduced under her leadership have made the journals more practical and public health-relevant. For instance, Dr Audin fostered the United States Department of Agriculture’s Food Safety and Inspection Service (USDA-FSIS ‘Inspection Insights’ - a public health-oriented food safety monthly column related to meat, poultry and egg products - from 1996 through 1998. She also increased international manuscript submissions.On 23 March 2009 AVMA Executive Vice President Dr W. Ron DeHaven named Dr Audin as editor-in-chief emeritus of the Publications Division. Wisely, it also meant that Dr Audin could continue contributing to the staff effort to ensure the high quality of the AVMA scientific journals

  11. Caffeinated-beverage consumption and its association with socio-demographic characteristics and self-perceived academic stress in first and second year students at the University of Puerto Rico Medical Sciences Campus (UPR-MSC).

    Science.gov (United States)

    Ríos, Josué L; Betancourt, Jesmari; Pagán, Ideliz; Fabián, Carla; Cruz, Sonia Y; González, Anaisa M; González, Michael J; Rivera-Soto, Winna T; Palacios, Cristina

    2013-06-01

    To determine the association between caffeinated-beverage consumption, self-perceived academic load, and self-perceived stress levels in first and second year students at UPR-MSC. A descriptive epidemiological study was performed using a self-administered anonymous questionnaire given to a representative stratified sample of 275 students. Questions included information regarding socio-demographic characteristics, academic load and stress indicators, and caffeinated-beverage consumption. Chi2 was used to assess the associations between these variables. Most participants were women (68%), aged 21-30 years (88%), with low annual household incomes (43%). Most perceived their academic loads as being heavy (68%), and most perceived their academic stress levels as being moderate (37%). Academic load was significantly correlated with stress level (pstress, and many (49%) reported that these beverages were useful for coping with stress. Energy drinks, in particular, were consumed more often by men compared to women (pstress or load. Consuming caffeinated beverages is a popular practice among participants in this sample, with soft drinks and coffee being the ones that are the most frequently consumed. No associations were found between the consumption of caffeinated beverages and academic stress or load.

  12. 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.

  13. USA üritab Assange'i ja sõnavabadust risti lüüa / Birgitta Jónsdóttir ; intervjueerinud Askur Alas

    Index Scriptorium Estoniae

    Jónsdóttir, Birgitta

    2011-01-01

    Intervjuu Islandi parlamendisaadiku ja Wikileaksi endise kaastöötajaga USA nõudmisest, et Twitter annaks USA-le saadiku isiklikku infot, põhjusest, miks ta pole enam Wikileaksiga seotud. Ta usub, et samasuguseid internetisaite ja organisatsioone tekib veelgi

  14. Piezoelectric Actuator Modeling Using MSC/NASTRAN and MATLAB

    Science.gov (United States)

    Reaves, Mercedes C.; Horta, Lucas G.

    2003-01-01

    This paper presents a procedure for modeling structures containing piezoelectric actuators using MSCMASTRAN and MATLAB. The paper describes the utility and functionality of one set of validated modeling tools. The tools described herein use MSCMASTRAN to model the structure with piezoelectric actuators and a thermally induced strain to model straining of the actuators due to an applied voltage field. MATLAB scripts are used to assemble the dynamic equations and to generate frequency response functions. The application of these tools is discussed using a cantilever aluminum beam with a surface mounted piezoelectric actuator as a sample problem. Software in the form of MSCINASTRAN DMAP input commands, MATLAB scripts, and a step-by-step procedure to solve the example problem are provided. Analysis results are generated in terms of frequency response functions from deflection and strain data as a function of input voltage to the actuator.

  15. Expansion and Harvesting of hMSC-TERT

    DEFF Research Database (Denmark)

    Weber, Christian; Pohl, Sebastian; Pörtner, Ralf

    2007-01-01

    The expansion of human mesenchymal stem cells as suspension culture by means of spinner flasks and microcarriers, compared to the cultivation in tissue culture flasks, offers the advantage of reducing the requirements of large incubator capacities as well as reducing the handling effort during cu...

  16. A case study of a microsystems MSc curriculum

    NARCIS (Netherlands)

    Mouthaan, A.J.

    2004-01-01

    This paper tries to define the contents of master's programmes in Nanotechnology or Nanoengineering. This emerging technology holds large promises for industrial innovation and we need to prepare graduates properly as they will be confronted for most of their future careers with these new

  17. Field-ion microscopy, MSC report No. 4691

    International Nuclear Information System (INIS)

    Seidman, D.N.

    1982-03-01

    This short article discusses the elements of a basic field ion microscope (FIM), the physics of the processes of field ionization and field evaporation, the factors limiting atomic resolution, the principle features of an atom probe FIM and imaging atom-probe mass spectroscopy

  18. MULTIDISCIPLINARY TEACHING – MSc COURSE ON TEAMWORK AND OPARATION

    DEFF Research Database (Denmark)

    Karlshøj, Jan; Dederichs, Anne

    2011-01-01

    focus on teamwork did not lead to a improvement of the team work in contrary. The team-structure was generally flat and decisions were mostly made in consensus. It is worthwhile to offer a multidisciplinary course and give engineering students experience in collaboration methods....... during the design phase; as well as a need of new work methods within the process. This calls for employees who are experienced in collaborating in interdisciplinary teams. To fulfill this demand a multidisciplinary course in “Advanced building design” has been developed at the Technical University...... of Denmark. The goal of the course is to provide training in teamwork at the final stage of the engineering education. The course has been carried out twice. It was held by a multidisciplinary team of professors in periods 2008/09, 2009/10 and 20010/2011. Teams of students were subject of a questionnaire...

  19. Organization of BSc and MSc projects in project families

    DEFF Research Database (Denmark)

    Ottosen, Lisbeth M.; Goltermann, Per; Jensen, Pernille Erland

    2014-01-01

    This work reports organization of student thesis projects in project families, with the benefit to both teaching and learning. The project organization went from student projects broadly distributed on topics related to different research issues and individual supervision to project families with...

  20. Factors that influence MSc (Med) (Pharmacy) completion rates at the ...

    African Journals Online (AJOL)

    %). Only 35.5% of part-time postgraduates and those who communicated more frequently with their supervisors received their degree. Those who completed their degree also scored higher on quality of communication with and accessibility of ...

  1. Mõttekilde fantaasialennust suvelavadel / Tiiu Levald

    Index Scriptorium Estoniae

    Levald, Tiiu, 1940-

    2010-01-01

    Birgitta festivalil etendunud Glucki ooperist "Orpheus ja Eurydike", lavastaja Georg Rootering, R. Wagneri ooperist "Lohengrin", lavastaja Kaspar Holten ja G. Rossini ooperist "Sevilla habemeajaja", lavastaja Eliah Moshinsky

  2. Жаркое и десерт на фестивале Birgitta / Айвар Лоог

    Index Scriptorium Estoniae

    Лоог, Айвар

    2010-01-01

    Richard Wagneri "Lohengrin", lavastaja Kasper Holten ja Gioachino Rossini "Sevilla habemeajaja", lavastaja Elijah Moshinsky. Mõlemad Moskva "Новая Опера" lavastused (The Kolobov Novaya Opera Theatre)

  3. 14 Review Oncocerciasis Wani MG MBchB, MMed (ophth), MSc ...

    African Journals Online (AJOL)

    Angel_D

    E-mail wanimena@mweb.co.zw. Abstract .... in clinical picture which may be related to pathogen city of Oncocerca volvulus, vector biting habits ... nerve. The first sign of ocular involvement is the inversion of the anterior segment ... immediately to a drop of normal saline or distilled water on a microscope slide and examined ...

  4. Formal methods impact on ANSI standard HL7/IM: filling gaps in MSC theory

    NARCIS (Netherlands)

    W. Wesselink; N. Goga (Nicolae); A.J. Mooij (Arjan); R. Spronk

    2005-01-01

    htmlabstractHealth level seven (HL7) is an ANSI standard that provides a comprehensive framework for electronic health information. The most-widely used HL7 specification is called infrastructure management, which facilitates health-care applications to exchange key sets of clinical and

  5. Hydroxychloroquine decreases human MSC-derived osteoblast differentiation and mineralization in vitro

    NARCIS (Netherlands)

    T. Both (Tim); van de Peppel, H.J. (H. Jeroen); M.C. Zillikens (Carola); M. Koedam (Marijke); J.P.T.M. van Leeuwen (Hans); P.M. van Hagen (Martin); P.L.A. van Daele (Paul); B.C.J. van der Eerden (Bram)

    2018-01-01

    textabstractWe recently showed that patients with primary Sjögren Syndrome (pSS) have significantly higher bone mineral density (BMD) compared to healthy controls. The majority of those patients (69%) was using hydroxychloroquine (HCQ), which may have favourable effects on BMD. To study the direct

  6. A new MSc course on diagnostics of electrical machines and power electronics

    DEFF Research Database (Denmark)

    Leban, Krisztina Monika; Ritchie, Ewen

    2011-01-01

    students. Additionally, specific subjects requested by participants, basic diagnosis and testing methods were presented during the lectures and workshops. General engineering knowledge about electric machines, power electronics and the combination of these was presented. The laboratory method, experiments...

  7. Snježana Malić-Limari, MSc in Natural Sciences

    Directory of Open Access Journals (Sweden)

    Sven Jelaska

    2010-06-01

    Full Text Available Snježana Malić-Limari successfully defended her Master’s thesis Evaluation of Medvednica Nature Park with Respect to Land Cover, Landform and Visitor System at the Faculty of Science of the University of Zagreb on November 23, 2009. The Master’s thesis was evaluated by the following Committee: Prof. Dr. Božena Mitić, Assist. Prof. Dr. Sven Jelaska (mentor and Prof. Dr. Sanja Tišma, Institute for International Relations.

  8. Developments in the Curriculum for the Swedish MSc Programme in Agriculture.

    Science.gov (United States)

    Malmfors, Birgitta; Nilsson, Kjell-Arne

    In Sweden, higher education in agriculture is provided exclusively by the Swedish University of Agricultural Sciences. The 130 students admitted to the Master of Science program in agriculture annually may choose to specialize in one of six specialty areas (plant science, animal science, food science, biotechnology, economics, and engineering),…

  9. Polycaprolactone nanomesh cultured with hMSC evaluated by synchrotron tomography

    DEFF Research Database (Denmark)

    Nygaard, Jens Vinge; Andersen, Morten Østergaard; Cloetens, Peter

    Introduction Cell response is closely related to substrate stiffness. Successful induced tissue repair from bioengineered constructs must possess both optimal bioactivity and mechanical strength. This is because cell interaction with the extracellular matrix (ECM) produces two different but concu......Introduction Cell response is closely related to substrate stiffness. Successful induced tissue repair from bioengineered constructs must possess both optimal bioactivity and mechanical strength. This is because cell interaction with the extracellular matrix (ECM) produces two different...... 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...... borders. Naked scaffolds and scaffolds cultivated statically with human bone marrow stromal cells, [3], for 24 hours, 14 days, and 21 days and prepared for holo-tomography. Synchrotron generated hard X-rays were used to perform quantitative phase sensitive holo-tomography at the ID19 beamline to obtain...

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

    Science.gov (United States)

    2015-03-27

    Transport phenomena. New York: Wiley; 1960. [52] Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006;98:1076e84. [53... Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol 2009;217:318e24. [54] Dennis JE, Cohen N, Goldberg VM, Caplan AI. Targeted delivery

  11. BEd, MSc, PhD, Senior Research Officer, Centre for Biotechnology ...

    African Journals Online (AJOL)

    2001-11-01

    Nov 1, 2001 ... on bancroftian filariasis in Kenya, from the time it was first documented in .... houses were Aedes aegypti and Culex fatigans with infection rates of ..... the mosquito biting densities, they exerted a very strong suppressive effect ...

  12. Upgrading and extended testing of the MSC integrated water and waste management hardware

    Science.gov (United States)

    Bambenek, R. A.; Nuccio, P. P.; Hurley, T. L.; Jasionowski, W. J.

    1972-01-01

    The results are presented of upgrading and testing an integrated water and waste management system, which uses the compression distillation, reverse osmosis, adsorption filtration and ion-exchange processes to recover potable water from urine, flush water and used wash water. Also included is the development of techniques for extending the useful biological life of biological filters, activated carbon filters and ion-exchange resins to at least 30 days, and presterilizing ion-exchange resins so that sterile water can be recovered from waste water. A wide variety of reverse osmosos materials, surfactants and germicides were experimentally evaluated to determine the best combination for a wash water subsystem. Full-scale module tests with real wash water demonstrated that surface fouling is a major problem.

  13. An (even) broader perspective: Combining environmental processes and natural hazards education in a MSc programme

    Science.gov (United States)

    Heckmann, Tobias; Haas, Florian; Trappe, Martin; Cyffka, Bernd; Becht, Michael

    2010-05-01

    Natural hazards are processes occurring in the natural environment that negatively affect human society. In most instances, the definition of natural hazards implies sudden events as different as earthquakes, floods or landslides. In addition, there are other phenomena that occur more subtly or slowly, and nevertheless may have serious adverse effects on the human environment. Hence, a comprehensive study programme in natural hazards has to include not only the conspicuous causes and effects of natural catastrophes, but of environmental processes in general. Geography as a discipline is located at the interface of natural, social and economic sciences; the physical geography programme described here is designed to include the social and economic dimension as well as management issues. Modules strengthening the theoretical background of geomorphic, geological, hydrological and meteorological processes and hazards are complemented by practical work in the field and the laboratory, dealing with measuring and monitoring environmental processes. On this basis, modeling and managing skills are developed. Another thread in the transdisciplinary programme deals with sustainability and environmental policy issues, and environmental psychology (e.g. perception of and reaction to hazards). This will improve the communication and team working skills of students wherever they are part of an interdisciplinary working group. Through the involvement in research programmes, students are confronted ‘hands on' with the different aspects of environmental processes and their consequences; thus, they will be excellently but not exclusively qualified for positions in the ‘natural hazards' sector.

  14. Factors Affecting Formation of R&D Alliance : Case of MSC Companies

    OpenAIRE

    Chen, Nick Kid Khian

    2005-01-01

    Confronted with the opening of world markets and intensified competition, companies at the Multimedia Super Corridor are searching for innovation through R&D. In their quest for efficient operation, firms increasingly revert to seeking new technologies via interfirm agreements, not only with suppliers and customers but also with competitors. The advantages of R&D alliance will be explored in this paper. The survey conducted using questionnaires sent by mail focused on three big areas, the mot...

  15. Mozarti spirituaalne sadomaso / Alvar Loog

    Index Scriptorium Estoniae

    Loog, Alvar, 1975-

    2006-01-01

    11.-20. augustini Birgitta festivali raames Pirita kloostri varemetes etendunud Mozarti ooperist "Tituse halastus" (Moskva Helikoni teatri esituses), Tallinna raekojas etendunud Mozarti intermezzo-komöödiast "Apollo ja Hyacinthus"

  16. Inimhääle lummus ja topeltverism / Tiiu Levald

    Index Scriptorium Estoniae

    Levald, Tiiu, 1940-

    2008-01-01

    Birgitta festivali raames 10. ja 11. VIII Pirita kloostris toimunud etendustest - Mascagni "Talupoja au", Leoncavallo "Pajatsid" ja Donizetti "Maria Stuart" Moskva Novaja Opera esituses, dirigendid: Eri Klas, Valeri Kritskov ja Sergei Lõssenko

  17. Keerukas terminal valiti aasta betoonehitiseks / Aivo Vahemets

    Index Scriptorium Estoniae

    Vahemets, Aivo

    2002-01-01

    Aasta Betoonehitise nimetuse võitis Muuga kuivpuisteainete terminal, projekteerija Randväli&Karema AS. Eriauhind arhitektuurse osa eest - Birgitta klooster Pirital. Eriauhind tellijale - büroohoone Tallinnas Toompuiestee 33. Eriauhind ehitajale - konteinerterminal Muugal, projekteerija AS Merin

  18. Pirita kloostri asutamine ja ülesehitamine 1407-1436 Rootsi allikate valguses / Ruth Rajamaa

    Index Scriptorium Estoniae

    Rajamaa, Ruth

    2007-01-01

    Birgitiinide ordu asutamisest ja arengust, Püha Birgitta Liivimaa kloostri algusest, Vadstena kloostri abistavast ja korralekutsuvast osast Pirita tütarkloostri asutamisel aastal 1407 kuni iseseisvaks kloostriks pühitsemisel 1431

  19. Amor meus, Cruxifixus est! / Teresa Perciaccante ; tõlk. Anne Kalling

    Index Scriptorium Estoniae

    Perciaccante, Teresa

    2002-01-01

    Kevadisest kriisist Petlemmas, mil Iisraeli armee piiras Jeesus Kristuse sünnikirikut. Ema Teresa Perciaccante kiri Pühima Päästja Püha Birgitta ordu ülemaabtissile Ema Tekla Famigliettile Rooma

  20. Photos of the conference

    Directory of Open Access Journals (Sweden)

    Birgitta Åhman

    1984-05-01

    Full Text Available Birgitta  Åhman is the photographer of the series of pictures from the conference, also for the cover photo of the full paper edition showing Kongsvold Mountain Hut and Biological Station.

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

    Science.gov (United States)

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

    2016-03-01

    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. Biological analyses were performed to evaluate the effect of scaffold materials on cellular behavior in terms of proliferation and early osteogenic differentiation of human Mesenchymal Stem Cells. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 726-733, 2016. © 2015 Wiley Periodicals, Inc.

  2. Modification of Silk Fibroin Using Diazonium Coupling Chemistry and the Effects on hMSC Proliferation and Differentiation

    Science.gov (United States)

    Murphy, Amanda R.; John, Peter St.; Kaplan, David L.

    2009-01-01

    A simple chemical modification method using diazonium coupling chemistry was developed to tailor the structure and hydrophilicity of silk fibroin protein. The extent of modification using several aniline derivatives was characterized using UV/vis and 1H NMR spectroscopy, and the resulting protein structure was analyzed with ATR-FTIR spectroscopy. Introduction of hydrophobic functional groups facilitated rapid conversion of the protein from a random coil to a β-sheet structure, while addition of hydrophilic groups inhibited this process. hMSCs were grown on these modified silks to assess the biocompatibility of these materials. The hydrophilicity of the silk derivatives was found to affect the growth rate and morphology, but hMSCs were able to attach, proliferate and differentiate into an osteogenic lineage on all of the silk derivatives. PMID:18417206

  3. Pure titanium particle loaded nanocomposites: study on the polymer/filler interface and hMSC biocompatibility.

    Science.gov (United States)

    Avolio, Roberto; D'Albore, Marietta; Guarino, Vincenzo; Gentile, Gennaro; Cocca, Maria Cristina; Zeppetelli, Stefania; Errico, Maria Emanuela; Avella, Maurizio; Ambrosio, Luigi

    2016-10-01

    The integration of inorganic nanoparticles into polymer matrices allows for the modification of physical properties as well as the implementation of new features for unexplored application fields. Here, we propose the study of a new metal/polymer nanocomposite fabricated by dispersing pure Ti nanoparticles into a poly(methylmetacrilate) matrix via solvent casting process, to investigate its potential use as new biomaterial for biomedical applications. We demonstrated that Ti nanoparticles embedded in the poly(methylmetacrilate) matrix can act as reinforcing agent, not negatively influencing the biological response of human mesenchymal stem cell in terms of cytotoxicity and cell viability. As a function of relative amount and surface treatment, Ti nanoparticles may enhance mechanical strength of the composite-ranging from 31.1 ± 2.5 to 43.7 ± 0.7 MPa-also contributing to biological response in terms of adhesion and proliferation mechanisms. In particular, for 1 wt% Ti, treated Ti nanoparticles improve cell materials recognition, as confirmed by higher cell spreading-quantified in terms of cell area via image analysis-locally promoting stronger interactions at cell matrix interface. At this stage, these preliminary results suggest a promising use of pure Ti nanoparticles as filler in polymer composites for biomedical applications.

  4. Double printing of hyaluronic acid/poly(glycidol) hybrid hydrogels with poly(ϵ-caprolactone) for MSC chondrogenesis

    NARCIS (Netherlands)

    Stichler, Simone; Böck, Thomas; Paxton, Naomi; Bertlein, Sarah; Levato, Riccardo; Schill, Verena; Smolan, Willi; Malda, Jos; Teßmar, Jörg; Blunk, Torsten; Groll, Jürgen

    2017-01-01

    This study investigates the use of allyl-functionalized poly(glycidol)s (P(AGE-co-G)) as a cytocompatible cross-linker for thiol-functionalized hyaluronic acid (HA-SH) and the optimization of this hybrid hydrogel as bioink for 3D bioprinting. The chemical cross-linking of gels with 10 wt.% overall

  5. Negotiating and Designing Public Space. Experiences with a new M.Sc. in Urban Design Program in Hong Kong

    Directory of Open Access Journals (Sweden)

    Hendrik Tieben

    2013-05-01

    Full Text Available This contribution reflects on first experiences made with a newly launched Master of Science in Urban Design program at the Chinese University of Hong Kong. As an important part of this program, students have to develop their design proposal in response to feedback of different stakeholders and community members. Thus the program responds to the growing aspiration of Hong Kong’s citizens to shape the urban development of their city and a lack of a meaningful participation process in the region. With its high density, protected country parks, efficient public transport and large scale housing program, generally, Hong Kong offers important lessons for contemporary urbanism. However, since the end of the British colonial rule and in face of increasing property prices, pollution and the disappearance of local heritage, intensive debates started about the regions future. Another central point of the recent discussion in Hong Kong – and key theme of the new urban design program - is the demand for the rights and qualities of public space. The paper presents the set-up of the design studio, which was closely linked to a course on “urban processes”. During the semester, students had to organize community forums and street exhibitions in a specific district, invite stakeholders and residents and discuss with them their ideas. Their projects, then, had to respond on the various feedbacks and integrate them in their design and policy proposals. The text reflects on the student projects and the lessons learned in the process. It addresses general questions such as the challenges in communicating with a diverse community (e.g. language barriers and culturally different ideas of public space. It addresses the question of the intended and unintended effects of a participatory design studio in the community, and possible follow-ups. And it reflects on the general role of design and designers in shaping community spaces.

  6. Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

    Science.gov (United States)

    Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

    2011-11-01

    Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration

    Science.gov (United States)

    Meng, Qingyang; Man, Zhentao; Dai, Linghui; Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Shao, Zhenxing; Zhu, Jingxian; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Ao, Yingfang

    2015-12-01

    Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.

  8. 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.

  9. Direct determination of a radiation-damage profile with atomic resolution in ion-irradiated platinum. MSC report No. 5030

    International Nuclear Information System (INIS)

    Pramanik, D.; Seidman, D.N.

    1983-05-01

    The field-ion microscope (FIM) technique has been employed to determine directly a radiation damage profile, with atomic resolution, in a platinum specimen which had been irradiated at 80 0 K with 20-keV Kr + ions to a fluence of 5 x 10 12 cm - 2 . It is shown that the microscopic spatial-vacancy distribution (radiation-damage profile) is directly related to the elastically-deposited-energy profile. The experimentally constructed radiation-damage profile is compared with a theoretical damage profile - calculated employing the TRIM Monte Carlo code - and excellent agreement is obtained between the two, thus demonstrating that it is possible to go directly from a microscopic spatial distribution of vacancies to a continuous radiation-damage profile

  10. The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice

    OpenAIRE

    Fakharzadeh, Saideh; Sahraian, Mohammad Ali; Hafizi, Maryam; Kalanaky, Somayeh; Masoumi, Zahra; Mahdavi, Mehdi; Kamalian, Nasser; Minagar, Alireza; Nazaran, Mohammad Hassan

    2014-01-01

    Saideh Fakharzadeh,1 Mohammad Ali Sahraian,2 Maryam Hafizi,1 Somayeh Kalanaky,1 Zahra Masoumi,1 Mehdi Mahdavi,1 Nasser Kamalian,3 Alireza Minagar,4 Mohammad Hassan Nazaran1 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Pathology, Medical School of Tehran University of Medical Sciences, Tehran, Iran; 4Department of Neurology, LSU Health Science...

  11. Phenotypic modulation of auto-reactive cells by insertion of tolerogenic molecules via MSC-derived exosomes.

    Science.gov (United States)

    Mokarizadeh, Aram; Delirezh, Nowruz; Morshedi, Ahhmad; Mosayebi, Ghasem; Farshid, Amir-Abbas; Dalir-Naghadeh, Bahram

    2012-01-01

    Auto-reactive cells-mediated immune responses are responsible for the current tissue damages during autoimmunity. Accordingly, functional modulation of auto-reactive cells has been a pivotal aim in many of recent studies. In the current study, we investigated the possibility for insertion of regulatory molecules onto auto-reactive cells through exosomal nano-shuttles as a novel approach for phenotype modification of auto-reactive cells. The exosomes were isolated from supernatant of mesenchymal stem cells culture. Resultant exosomes co-cultured with lymphocytes were harvested from established EAE mice in the presence of antigenic MOG35-55 peptide. After 24 hr, insertion of exosomal tolerogenic molecules (PD-L1, TGF-β, galectin-1) onto auto-reactive cells were explored through flow cytometry. The potency of exosomal inserted membrane molecules to modulate phenotype of auto-reactive lymphocytes was assessed upon ELISA test for their-derived cytokines IFN-γ and IL-17. Incorporation of exosomal molecules into lymohocytes' membrane was confirmed by flow cytometric analyses for surface levels of mentioned molecules. Additionally, the decreased secretion of IFN-γ and IL-17 were detected in exosome pre-treated lymphocytes upon stimulation with MOG peptide. Mesenchymal stem cells -derived exosomes showed to be efficient organelles for insertion of bioactive tolerogenic molecules onto auto-reactive cells and modulation of their phenotypes.

  12. A Comparison of the Optimization and Analysis of Doubly Curved Shells Using MSC/NASTRAN and ASTROS

    Science.gov (United States)

    1990-12-01

    BMC(7,5)=I.OD+00 CALL BMAT (X1,RI,X2,R2,0.OD+00,B,DL) CALL EMAT(DNU,E,T,G) C C DO BMC*E*B C DO 100 J1=1,7 DO 100 J2=1,5 DO 100 J3=1,5 DO 100 J4=1,6...ELEMENT LENGTH. C SUBROUTINE BMAT (XI,RI,X2,R2,DKSI,B,DL) DOUBLE PRECISION XI,RI,X2,R2,DKSI,B(S,6),DL,R,PHI,CPR,SPR,R, &DKMDKP, DLINV C C EXPLANATION OF

  13. E-learning for sustainable development - rationale, strategies, choices and actions. Experiences from the study programme MSc in Development Management

    Directory of Open Access Journals (Sweden)

    Sven Åke Bjørke

    2011-11-01

    Full Text Available The concept of e-learning is vague. ICT-supported education, online education, distance education, e-teaching and e-learning – what is the difference? This article describes the differences and practical pedagogical consequences depending on the choices made and is based on a concrete example and experiences. Modern ICT-supported educational methods demand awareness of various classifications of knowledge when developing curricula and appropriate learning activities.In the quest for a more sustainable development, there are now opportunities to leapfrog several stages. The education sector may jump directly to state of the art in e-pedagogy for building blended or purely online learning environments. To achieve this, investments in the training of teachers might be even more crucial than investing in the technology.

  14. Preliminary Evaluation of Yield and Yield Components of Some Khorasanian Sesame Ecotypes (Sesamum indicum L.

    Directory of Open Access Journals (Sweden)

    A. Nezami

    2014-09-01

    Full Text Available In most region of Khorasan, sesame ecotypes have been planted for many years, but there is little information about seed yield and yield components of them. Therefore a field experimental was conducted to investigation of yield parameters of 14 sesame ecotypes (MSC1, MSC2, MSC3, MSC4, MSC5, MSC6, MSC7, MSC8, MSC9, MSC10, MSC11, MSC12, MSC13 and MSC14 in randomized complete block design with three replications at experimental station, Collage of Agriculture, Ferdowsi University of Mashhad during 2009. Results showed that there were significant difference (P

  15. Education and the Child Labor Paradox Today. Essay Review of "Children on the Streets of the Americas" (Roslyn A. Mickelson, editor); "The Policy Analysis of Child Labor: A Comparative Study" (Christiaan Grootaert, Harry Anthony Patrinos); "What Works for Working Children?" (Jo Boyden, Birgitta Ling, William Myers); "Child Employment in Britain: A Social and Psychological Analysis" (Sandy Hobbs, Jim McKechnie); and "Bud, Not Buddy" (Christopher Paul Curtis).

    Science.gov (United States)

    Post, David

    2001-01-01

    Reviews five books on child labor, published 1997-2000, with reference to the International Labour Organization's 1999 convention that retreats from its previous hard stance on child labor. Discusses street children; public policy on child labor, child welfare, and school attendance; types of children's work; and working children as agents…

  16. "Design for All in the Context of the Information Society": Integration of a Specialist Course in a Generalist M.Sc. Program in Electrical and Electronics Engineering

    Science.gov (United States)

    Godino-Llorente, J. I.; Fraile, R.; Gonzalez de Sande, J. C.; Osma-Ruiz, V.; Saenz-Lechon, N.

    2012-01-01

    This paper describes an educational research experience that took place in the Electrical & Electronics Engineering Master's program offered at the Escuela Universitaria de Ingenieria Tecnica de Telecomunicacion, Universidad Politecnica de Madrid, Madrid, Spain. The focus is to provide details of the motivation behind and the design and…

  17. Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium.

    Science.gov (United States)

    Blocki, Anna; Beyer, Sebastian; Dewavrin, Jean-Yves; Goralczyk, Anna; Wang, Yingting; Peh, Priscilla; Ng, Michael; Moonshi, Shehzahdi S; Vuddagiri, Susmitha; Raghunath, Michael; Martinez, Eliana C; Bhakoo, Kishore K

    2015-06-01

    The limited efficacy of cardiac cell-based therapy is thought to be due to poor cell retention within the myocardium. Hence, there is an urgent need for biomaterials that aid in long-term cell retention. This study describes the development of injectable microcapsules for the delivery of mesenchymal stem cells (MSCs) into the infarcted cardiac wall. These microcapsules comprise of low concentrations of agarose supplemented with extracellular matrix (ECM) proteins collagen and fibrin. Dextran sulfate, a negatively charged polycarbohydrate, was added to mimic glycosaminoglycans in the ECM. Cell viability assays showed that a combination of all components is necessary to support long-term survival and proliferation of MSCs within microcapsules. Following intramyocardial transplantation, microcapsules degraded slowly in vivo and did not induce a fibrotic foreign body response. Pre-labeling of encapsulated MSCs with iron oxide nanoparticles allowed continued cell-tracking by MRI over several weeks following transplantation into infarcted myocardium. In contrast, MSCs injected as cell suspension were only detectable for two days post transplantation by MRI. Histological analysis confirmed integration of transplanted cells at the infarct site. Therefore, microcapsules proved to be suitable for stem cell delivery into the infarcted myocardium and can overcome current limitations of poor cell retention in cardiac cell-based therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Cultivation and Differentiation of Encapsulated hMSC-TERT in a Disposable Small-Scale Syringe-Like Fixed Bed Reactor

    DEFF Research Database (Denmark)

    Weber, Christian; Pohl, Sebastian; Pörtner, Ralf

    2007-01-01

    The use of commercially available plastic syringes is introduced as disposable small-scale fixed bed bioreactors for the cultivation of implantable therapeutic cell systems on the basis of an alginate-encapsulated human mesenchymal stem cell line. The system introduced is fitted with a noninvasiv...

  19. The process of undertaking a quantitative dissertation for a taught M.Sc: Personal insights gained from supporting and examining students in the UK and Ireland

    International Nuclear Information System (INIS)

    Marshall, Gill; Brennan, Patrick

    2008-01-01

    Purpose: This article discusses the roles of the student and the supervisor in the process of undertaking and writing a dissertation, a potentially daunting process. Results: The authors have supervised and examined students within 20 institutions and the personal insights gained result in the guidance provided within this article. Conclusion: The authors conclude that much can be done by students working with their supervisors, to improve progress in both performing and writing up the dissertation. Taking account of these factors will ease the dissertation process and move students progressively towards the production of a well-written dissertation

  20. Continuous bottom temperature measurements in strategic areas of the Florida Reef Tract at MSC Diego Restoration Site, 2004 - 2006 (NODC Accession 0014320)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This ongoing project began in 1988. A total of 38 subsurface recording thermographs have been deployed in the Florida Keys National Marine Sanctuary (FKNMS)and at...

  1. 2,2,2-Trifluoroethanol changes the transition kinetics and subunit interactions in the small bacterial mechanosensitive channel MscS

    NARCIS (Netherlands)

    Akitake, B.; Spelbrink, R.E.J.; Anishkin, A.; Killian, J.A.; de Kruijff, B.; Sukharev, S.

    2007-01-01

    2,2,2-Trifluoroethanol (TFE), a low-dielectric solvent, has recently been used as a promising tool to probe the strength of intersubunit interactions in membrane proteins. An analysis of inner membrane proteins of Escherichia coli has identified several SDS-resistant protein complexes that separate

  2. Status of research methods used in the dissertations of graduates from Tabriz University of Medical Sciences (Assistantship, MD, Board and MSc for the years 1996-2006

    Directory of Open Access Journals (Sweden)

    Abbas Doulani

    2010-03-01

    Full Text Available   The present study seeks to examine the status of research methods employed in dissertations submitted by graduates of Tabriz University of Medical Sciences. The study also examined the impact factors. Using content analysis, the research methods were divided into four groups: historical, descriptive, empirical and literature review. The distributions for each method were calculated on the basis of gender, graduate level, citations, time frame and fields of study. Samples were chosen randomly from among the dissertations available at faculty libraries at TUMS. 390 dissertations were selected. Findings demonstrated that gender did not influence the choice of research method. With exception of Nursing faculty, graduate level proved to be an prominent factor when choosing research method. All types of citations (books, journals, online and non-printed sources were identified as another significant factor impacting pushing towards any given research method. With exception of Hygiene and Food Faculty, the time factor affected the research method selection process as well. Finally, given their different research characteristics, the field of studies investigated also contributed to both the scope and direction of research methods chosen.

  3. Atomic-resolution study of homogeneous radiation-induced precipitation in a neutron-irradiated W-10 at. % Re alloy. MSC report No. 5014

    International Nuclear Information System (INIS)

    Herschitz, R.; Seidman, D.N.

    1983-06-01

    The phenomenon of radiation-induced precipitation has been investigated in a W-10 at. % Re alloy using the atom-probe field-ion microscope. Results show a significant alteration of the microstructure of this alloy as a result of the fast-neutron irradiation. Precipitates with the composition approx. WRe (sigma phase) were detected at a density of 10 16 cm -3 . Coherent, semicoherent and possibly incoherent precipitates of the sigma phase have been observed. They were not associated with either linear or planar defects, or with any impurity atoms; i.e. a true homogeneous radiation-induced precipitation occurs in this alloy. A physical argument is presented for the nucleation of the sigma phase precipitates in the vicinity of displacement cascades produced by primary knock-on atoms. It is suggested that the nucleation of the sigma phase is due to the formation of tightly-bound mobil mixed dumbells which react to form an immobile rhenium cluster. The growth of this cluster into a precipitate is most likely driven by the irreversible vacancy: self-interstitial atom (SIA) annihilation reaction, as suggested recently by Cauvin and Martin. A mechanism for the suppression of voids, in this alloy, is presented which is self-consistent with the homogeneous radiation-induced precipitation mechanism

  4. Differential effects of culture senescence and mechanical stimulation on the proliferation and leiomyogenic differentiation of MSC from different sources: implications for engineering vascular grafts.

    Science.gov (United States)

    Koobatian, Maxwell T; Liang, Mao-Shih; Swartz, Daniel D; Andreadis, Stelios T

    2015-04-01

    We examined the effects of senescence on the proliferation and leiomyogenic differentiation potential of mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs) or hair follicles (HF-MSCs). To this end, we compared ovine HF-MSCs and BM-MSCs in terms of their proliferation and differentiation potential to the smooth muscle cell lineage. We discovered that HF-MSCs are less susceptible to culture senescence compared with BM-MSCs. We hypothesized that application of mechanical forces may enhance the contractility and mechanical properties of vascular constructs prepared from senescent MSCs. Interestingly, HF-MSCs and BM-MSCs responded differently to changes in the mechanical microenvironment, suggesting that despite phenotypic similarities, MSCs from different anatomic locations may activate different pathways in response to the same microenvironmental factors. In turn, this may also suggest that cell-based tissue regeneration approaches may need to be tailored to the stem cell origin, donor age, and culture time for optimal results.

  5. A three-dimensional hierarchical collagen scaffold fabricated by a combined solid freeform fabrication (SFF) and electrospinning process to enhance mesenchymal stem cell (MSC) proliferation

    International Nuclear Information System (INIS)

    Ahn, SeungHyun; Kim, GeunHyung; Koh, Young Ho

    2010-01-01

    Collagen has the advantage of being very similar to macromolecular substances that can be recognized and metabolized in the biological environment. Although the natural material has superior property for this purpose, its use to fabricate reproducible and pore-structure-controlled 3D structures, which are designed to allow the entry of sufficient cells and the easy diffusion of nutrients, has been limited due to its low processability. Here, we propose a hybrid technology that combines a cryogenic plotting system with an electrospinning process. Using this technique, an easily pore-size-controllable hierarchical 3D scaffold consisting of micro-sized highly porous collagen strands and micro/nano-sized collagen fibers was fabricated. The pore structure of the collagen scaffold was controlled by the collagen micro/nanofibers, which were layered in the scaffold. The hierarchical scaffolds were characterized with respect to initial cell attachment and proliferation of bone marrow-derived mesenchymal stem cells within the scaffolds. The hierarchical scaffold exhibited incredibly enhanced initial cell attachment and cell compactness between pores of the plotted scaffold relative to the normally designed 3D collagen scaffold.

  6. Trend road safety measures : international course on transportation and road engineering in developing countries. Two-year postgraduate Diploma and M.Sc. programme.

    NARCIS (Netherlands)

    1991-01-01

    This course focuses mainly on traffic and transport in developing countries, and deals primarily with matters of infrastructure. Road safety and road safety problems are closely related to the construction and operation of the road network. (See also C 1341 - C1346).

  7. Influence of Mussel-Derived Bioactive BMP-2-Decorated PLA on MSC Behavior in Vitro and Verification with Osteogenicity at Ectopic Sites in Vivo.

    Science.gov (United States)

    Chen, Zhuoyue; Zhang, Zhen; Feng, Juantao; Guo, Yayuan; Yu, Yuan; Cui, Jihong; Li, Hongmin; Shang, Lijun

    2018-04-11

    Osteoinductive activity of the implant in bone healing and regeneration is still a challenging research topic. Therapeutic application of recombinant human bone morphogenetic protein-2 (BMP-2) is a promising approach to enhance osteogenesis. However, high dose and uncontrolled burst release of BMP-2 may introduce edema, bone overgrowth, cystlike bone formation, and inflammation. In this study, low-dose BMP-2 of 1 μg was used to design PLA-PD-BMP for functionalization of polylactic acid (PLA) implants via mussel-inspired polydopamine (PD) assist. For the first time, the binding property and efficiency of the PD coating with BMP-2 were directly demonstrated and analyzed using an antigen-antibody reaction. The obtained PLA-PD-BMP surface immobilized with this low BMP-2 dose can endow the implants with abilities of introducing strong stem cell adhesion and enhanced osteogenicity. Furthermore, in vivo osteoinduction of the PLA-PD-BMP-2 scaffolds was confirmed by a rat ectopic bone model, which is marked as the "gold standard" for the evidence of osteoinductive activity. The microcomputed tomography, Young's modulus, and histology analyses were also employed to demonstrate that PLA-PD-BMP grafted with 1 μg of BMP-2 can induce bone formation. Therefore, the method in this study can be used as a model system to immobilize other growth factors onto various different types of polymer substrates. The highly biomimetic mussel-derived strategy can therefore improve the clinical outcome of polymer-based medical implants in a facile, safe, and effective way.

  8. Uue sakraalarhitektuuri buum teise iseseisvuse aja Eestis / Egle Tamm, Urve Eslas

    Index Scriptorium Estoniae

    Tamm, Egle, 1969-

    2006-01-01

    Eesti kaasaegsest sakraalarhitektuurist. Tartu Metodisti Kirik, Viimse aja Pühade Jeesuse Kristuse Kirik (Tallinn), Tallinna Metodisti Kirik, EELK Viimsi Püha Jaakobi koguduse hoone, Tartu Salemi baptistikoguduse kirik, Jehoova tunnistajate kuningriigisaal (Tallinn), Uusapostliku Kiriku Keila koguduse hoone, Püha Birgitta ordu klooster ja kirik Pirital, Uusapostliku Kiriku Tartu koguduse hoone

  9. Dramatic music brings the opera to Estonia / Joel Alas

    Index Scriptorium Estoniae

    Alas, Joel

    2006-01-01

    Etendustest Birgitta Festivali raames 11.-22. aug. Tallinnas Pirita kloostris: Astor Piazzolla tango-ooperist "Maria de Buenos Aires" 11. aug., W. A. Mozarti ooper "Tituse halastus" Moskva Helikon Opera esituses 15. aug., Shostakovitshi ooper "Mtsenski maakonna Lady Macbeth" 17. augustil

  10. Sojuz muzõki i notshnõh sfer / Tamara Unanova

    Index Scriptorium Estoniae

    Unanova, Tamara

    2007-01-01

    Tallinnas Pirita kloostri varemetes Birgitta festivalil nähtust : Anton Rubinshteini ooper "Deemon" Moskva Novaja Opera esituses 16. aug., Arthur Honeggeri oratoorium "Jeanne d'Arc tuleriidal" 10. aug., Carl Orffi lavaline kantaat "Carmina Burana" 15. aug., lavastatud galakontsert filmikatketega ooperidiiva Maria Callasest 17. aug

  11. Maailmaklassi Donizetti ja Britten / Harry Liivrand

    Index Scriptorium Estoniae

    Liivrand, Harry, 1961-

    2008-01-01

    Tallinnas 8.-17. augustini väldanud Birgitta festivalil esitatud ooperitest: Gaetano Donizetti "Maria Stuart" Moskva Novaja Opera esituses (esietendus 11. aug.), Benjamin Britteni "Kruvi keere" (esietendus 15. aug.), Pietro Mascagni "Talupoja au" ja Ruggiero Leoncavallo"Pajatsid" 10. augustil

  12. Social Science Libraries Section. Special Libraries Division. Papers.

    Science.gov (United States)

    International Federation of Library Associations, The Hague (Netherlands).

    Three papers on the nonconventional literature and social science libraries were presented at the 1983 International Federation of Library Associations (IFLA) conference. In "Grey Material: A Scandinavian View," Birgitta Bergdahl (Sweden) outlines the etymology and meaning of the concept of "grey literature" (which can include…

  13. Pirita klooster tänasest ooperikires / Kersti Inno

    Index Scriptorium Estoniae

    Inno, Kersti, 1954-

    2006-01-01

    Birgitta Festivalist 11.-22. aug. Tallinnas Pirita kloostris. Astor Piazzolla tango-ooperist "Maria de Buenos Aires" (etendused 11. ja 12. aug. Pirita kloostri varemetes). Moskva Helikon Opera etendustest: 15. aug. Mozarti ooper "Tituse halastus" ja 17. aug. Shostakovitshi ooper "Mtsenski maakonna Lady Macbeth". Carl Orffi "Carmina Burana" 18. aug., Verdi "Reekviem" 19. aug. ja kontsert "Tuulatud Thule" 20. augustil

  14. Enne kui Rakvere teatrisse saabub vananaistesuvi / Pille-Riin Purje

    Index Scriptorium Estoniae

    Purje, Pille-Riin, 1963-

    2007-01-01

    Rakvere teatri suvest, valmistumisest suurejoonelise "Cyrano de Bergerac'i" väljatoomiseks septembris. Imaveres etendati William Shakespeare'i "MacBethi", Tallinnas Pirita kloostris avas 10. ja 11. augustil Birgitta Festivali Arthur Honeggeri-Paul Claudeli dramaatiline oratoorium "Jeanne d'Arc tuleriidal". Mõlemad lavastas Üllar Saaremäe

  15. Children who screen positive for autism at 2.5 years and receive early intervention: a prospective naturalistic 2-year outcome study

    OpenAIRE

    Spjut Jansson B; Miniscalco C; Westerlund J; Kantzer AK; Fernell E; Gillberg C

    2016-01-01

    Birgitta Spjut Jansson,1–3 Carmela Miniscalco,1,4 Joakim Westerlund,1,5 Anne-Katrin Kantzer,1,6 Elisabeth Fernell,1 Christopher Gillberg1 1Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, Institute of Neuroscience and Physiology, University of Gothenburg, 2Unit of Child and Adolescent Habilitation, 3Department of Psychology, University of Gothenburg, 4Division of Speech and Language Pathology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenbu...

  16. "Deemon" ja "Jeanne d'Arc" / Harry Liivrand

    Index Scriptorium Estoniae

    Liivrand, Harry, 1961-

    2007-01-01

    Anton Rubinshteini ooperist "Deemon" Moskva Novaja Opera esituses 16. aug., Arthur Honeggeri oratooriumist "Jeanne d'Arc tuleriidal" 10. aug., Piazolla tango-ooperist "Maria de Buenos Aires" 14. aug., Carl Orffi lavalisest kantaadist "Carmina Burana" 15. aug., lavastatud galakontserdist filmikatketega ooperidiiva Maria Callasest 17. aug. ja klassikalise ja dzhässballeti õhtutest Vene Keiserlikult balletitrupilt 18. ja 19. aug. Birgitta festivali raames Tallinnas Pirita kloostri varemetes

  17. Quantitative compositional analysis and field-evaporation behavior of ordered Ni4Mo on an atomic plane-by-plane basis: an atom-probe field-ion microscope study. MSC report No. 4802

    International Nuclear Information System (INIS)

    Yamamoto, M.; Seidman, D.N.

    1982-10-01

    The (211) fundamental and (101) superlattice planes, of the bct lattice, were analysed chemically on an atomic plane-by-plane basis. It was demonstrated that the composition of each individual plane can be determined as a function of depth without any ambiguity. The overall average Mo concentration was measured to be 17.1 at. % for the (211) fundamental plane. Details of the field evaporation behavior of the (211) fundamental and (101) superlattice planes were studied. The field-evaporation behavior is described in terms of the field-evaporation rate, the order of the field evaporated ions, etc. Each individual atomic plane field evaporated on an atomic plane-by-plane basis for the (211) fundamental plane. While for (101) superlattice plane a group of planes consisting of one plane of Mo atoms and four planes of Ni atoms field-evaporated as a unit. An abnormal increase in the number of Mo atoms was found in the central portion of the (211) fundamental plane. Possible mechanisms for the abnormal field evaporation rate are discussed. It is concluded that the atom probe technique can be used to follow the physics and chemistry of the field-evaporation process and the chemistry of the alloy as a function of position, on a subnanometer scale, throughout the specimen. 13 figures

  18. Evaluation of User Interface of DL + Federated Search Engine from the Perspective of M.A / M.S.C Students in Al-Zahra University in order to Provide Federated Search Engines User Interface Pattern

    Directory of Open Access Journals (Sweden)

    Amir Ghaebi

    2014-02-01

    The results showed that the major component from graduate students' perspective is guidance and navigation and searched filter components. Results indicate that more than 50 percent of students the importance of 74 criteria of 96 criteria considered high and very high and, (therefore the majority of the criteria in the study from the viewpoints are acceptable. However, findings also showed that among the four components of this study, the search filter, display and record review, consolidation and guidance is a positive relation, and between the views of different faculties is not significant difference about the importance of criterias and components.

  19. The first systematic analysis of 3D rapid prototyped poly(ε-caprolactone) scaffolds manufactured through BioCell printing: the effect of pore size and geometry on compressive mechanical behaviour and in vitro hMSC viability

    International Nuclear Information System (INIS)

    Domingos, M; Bartolo, P; Intranuovo, F; Russo, T; Santis, R De; Gloria, A; Ambrosio, L; Ciurana, J

    2013-01-01

    Novel additive manufacturing processes are increasingly recognized as ideal techniques to produce 3D biodegradable structures with optimal pore size and spatial distribution, providing an adequate mechanical support for tissue regeneration while shaping in-growing tissues. With regard to the mechanical and biological performances of 3D scaffolds, pore size and geometry play a crucial role. In this study, a novel integrated automated system for the production and in vitro culture of 3D constructs, known as BioCell Printing, was used only to manufacture poly(ε-caprolactone) scaffolds for tissue engineering; the influence of pore size and shape on their mechanical and biological performances was investigated. Imposing a single lay-down pattern of 0°/90° and varying the filament distance, it was possible to produce scaffolds with square interconnected pores with channel sizes falling in the range of 245–433 µm, porosity 49–57% and a constant road width. Three different lay-down patterns were also adopted (0°/90°, 0°/60/120° and 0°/45°/90°/135°), thus resulting in scaffolds with quadrangular, triangular and complex internal geometries, respectively. Mechanical compression tests revealed a decrease of scaffold stiffness with the increasing porosity and number of deposition angles (from 0°/90° to 0°/45°/90°/135°). Results from biological analysis, carried out using human mesenchymal stem cells, suggest a strong influence of pore size and geometry on cell viability. On the other hand, after 21 days of in vitro static culture, it was not possible to detect any significant variation in terms of cell morphology promoted by scaffold topology. As a first systematic analysis, the obtained results clearly demonstrate the potential of the BioCell Printing process to produce 3D scaffolds with reproducible well organized architectures and tailored mechanical properties. (paper)

  20. O Mestrado do Programa de Pós-graduação em Epidemiologia da UFPel baseado em consórcio de pesquisa: uma experiência inovadora UFPel's epidemiology MSc program based on research consortium: an innovative experience

    Directory of Open Access Journals (Sweden)

    Aluísio J. D. Barros

    2008-05-01

    Full Text Available O Programa de Pós-graduação em Epidemiologia da UFPel realizou um intenso trabalho de auto-avaliação para resolver problemas identificados com seu curso de mestrado. O resultado foi a introdução de uma estrutura curricular baseada em dois pilares. De um lado, disciplinas de cunho teórico, fornecendo a base da formação do mestrando; de outro, disciplinas de cunho prático, onde os alunos trabalham coletivamente a construção de seu projeto de pesquisa, passando pela escolha de um tema, revisão da literatura, definição de objetivos e da metodologia. Esse esforço conjunto culmina na realização de um trabalho de campo único, na forma de um estudo transversal de base populacional, em que todos os mestrandos participam de maneira integral, obtendo dados para sua dissertação. Essa estratégia tem garantido a formação de mestres em epidemiologia com forte base teórica e com experiência de preparação e condução de um trabalho de campo. Além disso, tem sido possível manter um tempo de titulação abaixo de 24 meses. Cerca de 80% dos egressos têm publicado pelo menos um artigo baseado em seu mestrado. Destas publicações, quase 90% têm se dado em periódicos classificados como Internacional-A no Qualis da Capes.The postgraduate program in epidemiology of the Federal University of Pelotas, Brazil, went through an intense self-assessment process to solve problems related to its Master's course. The result was the introduction of a curricular structure based on two pillars. The first one: theoretical courses to offer students the bases of epidemiology. The other, practical training in which students work in groups to design their research projects, from the choice of a research question, to literature review, definition of objectives and methods. This joint effort leads to shared fieldwork, a cross-sectional population-based study, where all students have full participation and get data for their dissertations. This strategy has provided students with strong theoretical background and experience in preparing and conducting fieldwork. Besides, a median completion time below 24 months has been achieved. About 80% of the students who complete the course published at least one paper based on their dissertations; and almost 90% of these papers were published in journals classified as A-International by the Qualis criteria established by Capes.

  1. Comparison of human expert and computer-automated systems using magnitude-squared coherence (MSC) and bootstrap distribution statistics for the interpretation of pattern electroretinograms (PERGs) in infants with optic nerve hypoplasia (ONH).

    Science.gov (United States)

    Fisher, Anthony C; McCulloch, Daphne L; Borchert, Mark S; Garcia-Filion, Pamela; Fink, Cassandra; Eleuteri, Antonio; Simpson, David M

    2015-08-01

    Pattern electroretinograms (PERGs) have inherently low signal-to-noise ratios and can be difficult to detect when degraded by pathology or noise. We compare an objective system for automated PERG analysis with expert human interpretation in children with optic nerve hypoplasia (ONH) with PERGs ranging from clear to undetectable. PERGs were recorded uniocularly with chloral hydrate sedation in children with ONH (aged 3.5-35 months). Stimuli were reversing checks of four sizes focused using an optical system incorporating the cycloplegic refraction. Forty PERG records were analysed; 20 selected at random and 20 from eyes with good vision (fellow eyes or eyes with mild ONH) from over 300 records. Two experts identified P50 and N95 of the PERGs after manually deleting trials with movement artefact, slow-wave EEG (4-8 Hz) or other noise from raw data for 150 check reversals. The automated system first identified present/not-present responses using a magnitude-squared coherence criterion and then, for responses confirmed as present, estimated the P50 and N95 cardinal positions as the turning points in local third-order polynomials fitted in the -3 dB bandwidth [0.25 … 45] Hz. Confidence limits were estimated from bootstrap re-sampling with replacement. The automated system uses an interactive Internet-available webpage tool (see http://clinengnhs.liv.ac.uk/esp_perg_1.htm). The automated system detected 28 PERG signals above the noise level (p ≤ 0.05 for H0). Good subjective quality ratings were indicative of significant PERGs; however, poor subjective quality did not necessarily predict non-significant signals. P50 and N95 implicit times showed good agreement between the two experts and between experts and the automated system. For the N95 amplitude measured to P50, the experts differed by an average of 13% consistent with differing interpretations of peaks within noise, while the automated amplitude measure was highly correlated with the expert measures but was proportionally larger. Trial-by-trial review of these data required approximately 6.5 h for each human expert, while automated data processing required automated computer system for PERG analysis, using a panel of signal processing and statistical techniques, provides objective present/not-present detection and cursor positioning with explicit confidence intervals. The system achieves, within an efficient and robust statistical framework, estimates of P50 and N95 amplitudes and implicit times similar to those of clinical experts.

  2. Estudio del sistema regulador formado por la serotonina y sus receptores en las células troncales MSC aisladas de médula ósea humana. Adipogénesis.

    OpenAIRE

    González Méndez, Laura

    2014-01-01

    Tesis doctoral inédita, leída en Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 21/03/2014 En los últimos años se ha identificado a la serotonina como un regulador crítico de la masa ósea, regulando tanto directa como indirectamente la actividad de las células responsables del proceso de remodelación ósea, osteoclastos y osteoblastos. El presente trabajo muestra que las MSCs aisladas de la médula ósea humana, células precursoras ...

  3. East African Medical Journal

    African Journals Online (AJOL)

    F. M. Gakuya, BVM, MSc, M.N.Kyule, BVM, MSc, PhD, P.B. Gathura, BVM, MSc, PhD, Department of Public Health, Pharmacology and Toxicology, University of. Nairobi, P.O. Box 29053, Nairobi, Kenya and S. Kariuki, BVM, MSc, PhD, CentreforMicrobiology Research, Kenya Medical Research Institute, P.O. Box54840, ...

  4. [Mesenchymal stem cells: weapons or dangers for cancer treatment?].

    Science.gov (United States)

    Lazennec, Gwendal

    2011-03-01

    Mesenchymal stem cells (MSC) have attracted recent attention for their cell therapy potential, based in particular on their immunosuppressive properties, which have served as the basis for the treatment of autoimmune diseases. Interestingly, MSC have been used in cell therapy strategies to deliver therapeutical genes. Cell therapy approaches taking advantages of MSC have been proposed, as MSC display a potential tropsim for tumors. However, all these strategies raise a series of questions about the safety of MSC, as MSC could enhance tumor growth and metastasis. This review summarizes recent findngs about MSC in carcinogenesis. © 2011 médecine/sciences - Inserm / SRMS.

  5. Mesenchymal stem cell-educated macrophages

    OpenAIRE

    Eggenhofer Elke; Hoogduijn Martin J

    2012-01-01

    Abstract Mesenchymal stem cells (MSC) mediate their immunosuppressive effects via a variety of mechanisms. One of these mechanisms involves the induction of macrophages with immunomodulatory capacities. This effect of MSC may be exploited when MSC are used as a cell therapeutic product. Furthermore, MSC are resident in tissues where they may locally target infiltrating macrophages to adapt more regulatory properties. The present review discusses the interaction between MSC and macrophages, th...

  6. Euroopas haruldane kloostrifestival / Heili Vaus-Tamm

    Index Scriptorium Estoniae

    Vaus-Tamm, Heili, 1961-

    2007-01-01

    Birgitta festivalil Pirita kloostri varemetes mängukavas: Arthur Honeggeri oratoorium "Jeanne d'Arc tuleriidal" (10. ja 11. aug., lavastajaks Üllar Saaremäe, peaosas Mirtel Pohla ja Benedictuse osatäitjaks Rain Simmul), Piazolla tango-ooper "Maria de Buenos Aires" (14. aug.), Carl Orffi lavaline kantaat "Carmina Burana" (15. aug.), A. Rubinshteini ooper "Deemon" (16. aug.), lavastatud galakontsert filmikatketega ooperidiiva Maria Callasest (17. aug.), klassikalise ja dzhässballeti õhtud Vene Keiserlikult balletitrupilt (18. ja 19. aug.)

  7. Suvefestivalid

    Index Scriptorium Estoniae

    2006-01-01

    2006. aasta suvel toimuvatest muusikaüritustest: Heliloojatele Kappidele pühendatud IX Suure-Jaani Muusikafestival, Nissi suvemuusika, Seitsme Linna muusika, Klaaspärlimäng, Pärnu ooperipäevad 2006, Tallinna XX orelifestival, Mravinski Festival 2006, Andrew Lloyd Webberi galaõhtu, Juu Jääb 2006 (retromuusikafestival), David Oistrahhi festival 2006, Hiiumaa VIII kammermuusikapäevad 2006, Viljandi vanamuusikafestival 2006, Rapla kirikumuusika XIV festival 2006, Haapsalu XIII keelpillimuusika festival, Kuressaare ooperipäevad 2006, Birgitta festival 2006, Võru Vaskpillipäevad 2006, Tallinna Kammermuusika festival 2006

  8. Morrissey

    Index Scriptorium Estoniae

    2009-01-01

    Laulja Morrissey kontserdist tuuri "Tour of Refusal" raames 4. juulil Tallinnas Rock Cafés, "IV Tallinna Kitarrifestivalist" 15.-20. juunil Mustpeade Majas, "Birgitta festivalist" 13.-23. augustil Pirita kloostris, rockmuusikafestivalist "Lelle Alternatiiv" 10.-12. juulil, "Tabasalu Jazz Festist" Rannamõisa kirikus ja Tabasalu keskväljakul 26.-27. juunil, muusikafestivalist "Klaaspärlimäng" Tartus ja Vormsil 16.-26. juulil, "VIII Eesti Noorte Heliloojate Festivalist" Tartu Jaani kirikus 4.-7. juunil, muusikafestivalist "Kumu ÖÖ" KUMUs 5. juunil, festivalist "Viru Folk" Käsmus 7.-9. augustil, "XVII Viljandi Pärimusmuusika Festivalist" 23.-26. juulil

  9. 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.

  10.  Usuario/a Ha iniciado sesión como joshua Mi perfil Cerrar Sesión Notificaciones Ver (159 Administrar  Contenido de la revista Herramientas del artículo Imprimir este artículo Metadatos de indexación Cómo citar un elemento Publicar un comentario Información Para los lectores/as Para los autores/as Para los bibliotecarios/as Acerca de los autores/as MSc. Ledys Mata Bravo MSc. Minerva Beis García MSc. María Caridad De Rojas Gómez Encuéntranos en... Inicio / Promoción de salud y autocuidado del sistema genitourinario en estudiantes de la Facultad de Tecnología de la Salud

    Directory of Open Access Journals (Sweden)

    MSc. Ledys Mata Bravo

    2016-06-01

    Full Text Available En el artículo se hizo un bosquejo del surgimiento de la promoción de salud y su papel en la capacitación de la población para ejercer un mayor control sobre las determinantes de su salud y mejorar así esta, como función central de la salud pública, que coadyuva a los esfuerzos invertidos para afrontar las enfermedades transmisibles, las no transmisibles y otras amenazas para la salud. Resultando de vital importancia detenernos en el estudio del comportamiento de las enfermedades más frecuentes en la población cubana, tales como: las infecciones del Sistema Genitourinario identificadas como las más frecuentes en la atención primaria de salud y una de las causas que desencadena enfermedades crónicas como la insuficiencia renal, el cáncer entre otras. De forma general las infecciones del sistema Genitourinario influyen en la apropiación de conocimiento por la ruptura del equilibrio, además atentan contra la procreación del hombre, incide en el aumento del ausentismo escolar y por tanto en la promoción escolar. En la Facultad de Tecnología de la Salud existe un gran por ciento de ausencias provocadas por estas infecciones que han llevado a la repitencia y arrastres de asignaturas debido a un mal manejo de ellas.

  11. Receptor control in mesenchymal stem cell engineering

    Science.gov (United States)

    Dalby, Matthew J.; García, Andrés J.; Salmeron-Sanchez, Manuel

    2018-03-01

    Materials science offers a powerful tool to control mesenchymal stem cell (MSC) growth and differentiation into functional phenotypes. A complex interplay between the extracellular matrix and growth factors guides MSC phenotypes in vivo. In this Review, we discuss materials-based bioengineering approaches to direct MSC fate in vitro and in vivo, mimicking cell-matrix-growth factor crosstalk. We first scrutinize MSC-matrix interactions and how the properties of a material can be tailored to support MSC growth and differentiation in vitro, with an emphasis on MSC self-renewal mechanisms. We then highlight important growth factor signalling pathways and investigate various materials-based strategies for growth factor presentation and delivery. Integrin-growth factor crosstalk in the context of MSC engineering is introduced, and bioinspired material designs with the potential to control the MSC niche phenotype are considered. Finally, we summarize important milestones on the road to MSC engineering for regenerative medicine.

  12. 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

    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......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...... transplanted subcutaneously into immunocompetent mice (n=12). Undifferentiated MSC (group A) were compared with osteogenic-induced MSC (group B). Human-specific in situ hybridization and anti-vimentin staining was used to follow MSC after transplantation. Quantitative evaluation of lymphocytes and macrophages...

  13. Decree no. 2001-1199 of the 10 december 2001 publishing the resolution MSC. 88 (71) notifying adoption of the international compilation of safety rules for the spent nuclear fuels, plutonium and high level radioactive wastes transport in casks on ships (compilation INF) (annexes), adopted at London the 27 may 1999; Decret no. 2001-1199 du 10 decembre 2001 portant publication de la resolution MSC.88 (71) portant adoption du recueil international de regles de securite pour le transport de combustible nucleaire irradie, de plutonium et de dechets hautement radioactifs en colis a bord de navires (recueil INF) (ensemble une annexe), adoptee a Londres le 27 mai 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-01

    This legislative text concerns the safety rules of spent nuclear fuels, plutonium and high level radioactive wastes transport, in casks on ships. Rules, fire prevention, temperature control of casks, electric supply, radioprotection, management and emergency plans are detailed. (A.L.B.)

  14. Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Xiaofang Yu

    Full Text Available Mesenchymal stem cell (MSC administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI by improving MSC migration to the injured kidney. Cobalt was used as hypoxia mimetic preconditioning (HMP. MSC were subjected to HMP through 24 h culture in 200 µmol/L cobalt. Compared to normoxia cultured MSC (NP-MSC, HMP significantly increased the expression of HIF-1α and CXCR4 in MSC and enhanced the migration of MSC in vitro. This effect was lost when MSC were treated with siRNA targeting HIF-1α or CXCR4 antagonist. SPIO labeled MSC were administered to rats with I/R injury followed immediately by magnetic resonance imaging. Imaging clearly showed that HMP-MSC exhibited greater migration and a longer retention time in the ischemic kidney than NP-MSC. Histological evaluation showed more HMP-MSC in the glomerular capillaries of ischemic kidneys than in the kidneys receiving NP-MSC. Occasional tubules showed iron labeling in the HMP group, while no tubules had iron labeling in NP group, indicating the possibility of tubular transdifferentiation after HMP. These results were also confirmed by fluorescence microscopy study using CM-DiI labeling. The increased recruitment of HMP-MSC was associated with reduced kidney injury and enhanced functional recovery. This effect was also related to the increased paracrine action by HMP-MSC. Thus we suggest that by enhancing MSC migration and prolonging kidney retention, hypoxic preconditioning of MSC may be a useful approach for developing AKI cell therapy.

  15. 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 ...... the translation of MSC into clinic: Generation of MSC-like cells from human pluripotent stem cells, strategies to enhance homing of MSC to injured tissues, and targeting of MSC in vivo.......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...

  16. Wnt signalling mediates the cross-talk between bone marrow derived pre-adipocytic and pre-osteoblastic cell populations

    DEFF Research Database (Denmark)

    Taipaleenmaki, Hanna; Abdallah, Basem M; Aldamash, Abdullah

    2011-01-01

    ) (mMSC(Bone)) or adipogenic (mMSC(Adipo)) lineage. To identify the molecular mechanism determining the lineage commitment, we compared the basal gene expression profile of mMSC(Bone) versus mMSC(Adipo) using Affymetrix GeneChip® MG430A 2.0 Array. Gene annotation analysis based on biological function...... revealed an over-representation of skeletal development genes in mMSC(Bone) while genes related to lipid metabolism and immune response were highly expressed in mMSC(Adipo). In addition, there was a significant up-regulation of canonical Wnt signalling genes in mMSC(Bone) compared to mMSC(Adipo) (p...

  17. Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells

    International Nuclear Information System (INIS)

    Nakanishi, Chiaki; Yamagishi, Masakazu; Yamahara, Kenichi; Hagino, Ikuo; Mori, Hidezo; Sawa, Yoshiki; Yagihara, Toshikatsu; Kitamura, Soichiro; Nagaya, Noritoshi

    2008-01-01

    Mesenchymal stem cells (MSC) transplantation has been proved to be promising strategy to treat the failing heart. The effect of MSC transplantation is thought to be mediated mainly in a paracrine manner. Recent reports have suggested that cardiac progenitor cells (CPC) reside in the heart. In this study, we investigated whether MSC had paracrine effects on CPC in vitro. CPC were isolated from the neonatal rat heart using an explant method. MSC were isolated from the adult rat bone marrow. MSC-derived conditioned medium promoted proliferation of CPC and inhibited apoptosis of CPC induced by hypoxia and serum starvation. Chemotaxis chamber assay demonstrated that MSC-derived conditioned medium enhanced migration of CPC. Furthermore, MSC-derived conditioned medium upregulated expression of cardiomyocyte-related genes in CPC such as β-myosin heavy chain (β-MHC) and atrial natriuretic peptide (ANP). In conclusion, MSC-derived conditioned medium had protective effects on CPC and enhanced their migration and differentiation

  18. Genetically-modified pig mesenchymal stromal cells: xenoantigenicity and effect on human T-cell xenoresponses.

    Science.gov (United States)

    Ezzelarab, Mohamed; Ezzelarab, Corin; Wilhite, Tyler; Kumar, Goutham; Hara, Hidetaka; Ayares, David; Cooper, David K C

    2011-01-01

    Mesenchymal stromal cells (MSC) are being investigated as immunomodulatory therapy in the field of transplantation, particularly islet transplantation. While MSC can regenerate across species barriers, the immunoregulatory influence of genetically modified pig MSC (pMSC) on the human and non-human primate T-cell responses has not been studied. Mesenchymal stromal cells from wild-type (WT), α1,3-galactosyltransferase gene knockout (GTKO) and GTKO pigs transgenic for the human complement-regulatory protein CD46 (GTKO/CD46) were isolated and tested for differentiation. Antibody binding and T-cell responses to WT and GTKO pMSC in comparison with GTKO pig aortic endothelial cells (pAEC) were investigated. The expression of swine leukocyte antigen (SLA) class II (SLA II) was tested. Costimulatory molecules CD80 and CD86 mRNA levels were measured. Human T-cell proliferation and the production of pro-inflammatory cytokines in response to GTKO and GTKO/CD46 pMSC in comparison with human MSC (hMSC) were evaluated. α1,3-galactosyltransferase gene knockout and GTKO/CD46 pMSC isolation and differentiation were achieved in vitro. Binding of human antibodies and T-cell responses were lower to GTKO than those to WT pMSC. Human and baboon (naïve and sensitized) antibody binding were significantly lower to GTKO pMSC than to GTKO pAEC. Before activation, human CD4(+) T-cell response to GTKO pMSC was significantly weaker than that to GTKO pAEC, even after pIFN-γ activation. More than 99% of GTKO/CD46 pMSC expressed hCD46. Human peripheral blood mononuclear cells and CD4(+) T-cell responses to GTKO and GTKO/CD46 pMSC were comparable with those to hMSC, and all were significantly lower than to GTKO pAEC. GTKO/CD46 pMSC downregulated human T-cell proliferation as efficiently as hMSC. The level of proinflammatory cytokines IL-2, IFN-γ, TNF-α, and sCD40L correlated with the downregulation of T-cell proliferation by all types of MSC. Genetically modified pMSC is significantly less

  19. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

    Science.gov (United States)

    Golpanian, Samuel; DiFede, Darcy L; Pujol, Marietsy V; Lowery, Maureen H; Levis-Dusseau, Silvina; Goldstein, Bradley J; Schulman, Ivonne H; Longsomboon, Bangon; Wolf, Ariel; Khan, Aisha; Heldman, Alan W; Goldschmidt-Clermont, Pascal J; Hare, Joshua M

    2016-03-15

    Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

  20. Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

    OpenAIRE

    Selleri, Silvia; Bifsha, Panojot; Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Ren?e; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle

    2016-01-01

    Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-...

  1. 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.

  2. Changes in markers of fatigue following a competitive match in elite ...

    African Journals Online (AJOL)

    P Phibbs,1,2 MSc; J Weakley,1,2 MSc; D Read,1,2 MSc; B Jones,1,2 PhD ... match fatigue in other junior collision sport athletes is also far less ... were performed on a portable force plate (400 Series Performance. Plate ... change was described as unclear. ... occurs during collisions,[11] may have further contributed to the.

  3. Military Sealift Command

    Science.gov (United States)

    school girl during a community outreach event. Religious Program Specialist 1st Class Jason Cooper school girl during a community outreach event. (U.S. Navy photo by MC1 Micah Blechner) Voyage Plan Index IG Hotline MSC EEO MSC SAPR Reasonable Accommodation Policy Anti-Harassment Policy About MSC This

  4. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

    Science.gov (United States)

    2012-07-01

    Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related...problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell (iPS) derived MSC

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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

  6. 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.

  7. Analysis of migration rate and chemotaxis of human adipose-derived mesenchymal stem cells in response to LPS and LTA in vitro

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

    Mesenchymal stem cells (MSC) are able to stimulate the regeneration of injured tissue. Since bacterial infections are common complications in wound healing, bacterial pathogens and their components come into direct contact with MSC. The interaction with bacterial structures influences the proliferation, differentiation and migratory activity of the MSC, which might be of relevance during regeneration. Studies on MSC migration in response to bacterial components have shown different results depending on the cell type. Here, we analyzed the migration rate and chemotaxis of human adipose-derived MSC (adMSC) in response to the basic cell-wall components lipopolysaccharide (LPS) of Gram-negative bacteria and lipoteichoic acid (LTA) of Gram-positive bacteria in vitro. To this end, we used transwell and scratch assays, as well as a specific chemotaxis assay combined with live-cell imaging. We found no significant influence of LPS or LTA on the migration rate of adMSC in transwell or scratch assays. Furthermore, in the µ-slide chemotaxis assay, the stimulation with LPS did not exert any chemotactic effect on adMSC. - Highlights: • LPS increased the release of IL-6 and IL-8 in adMSC significantly. • The migration rate of adMSC was not influenced by LPS or LTA. • LPS or LTA did not exert a chemotactic effect on adMSC.

  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. Analysis of migration rate and chemotaxis of human adipose-derived mesenchymal stem cells in response to LPS and LTA in vitro

    International Nuclear Information System (INIS)

    Herzmann, Nicole; Salamon, Achim; Fiedler, Tomas; Peters, Kirsten

    2016-01-01

    Mesenchymal stem cells (MSC) are able to stimulate the regeneration of injured tissue. Since bacterial infections are common complications in wound healing, bacterial pathogens and their components come into direct contact with MSC. The interaction with bacterial structures influences the proliferation, differentiation and migratory activity of the MSC, which might be of relevance during regeneration. Studies on MSC migration in response to bacterial components have shown different results depending on the cell type. Here, we analyzed the migration rate and chemotaxis of human adipose-derived MSC (adMSC) in response to the basic cell-wall components lipopolysaccharide (LPS) of Gram-negative bacteria and lipoteichoic acid (LTA) of Gram-positive bacteria in vitro. To this end, we used transwell and scratch assays, as well as a specific chemotaxis assay combined with live-cell imaging. We found no significant influence of LPS or LTA on the migration rate of adMSC in transwell or scratch assays. Furthermore, in the µ-slide chemotaxis assay, the stimulation with LPS did not exert any chemotactic effect on adMSC. - Highlights: • LPS increased the release of IL-6 and IL-8 in adMSC significantly. • The migration rate of adMSC was not influenced by LPS or LTA. • LPS or LTA did not exert a chemotactic effect on adMSC.

  10. p53 regulates the proliferation, differentiation and spontaneous transformation of mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Armesilla-Diaz, Alejandro, E-mail: aarmesilla@cib.csic.es [Department of Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid (Spain); Elvira, Gema; Silva, Augusto [Department of Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid (Spain)

    2009-12-10

    Mesenchymal stem cells (MSC) have been extensively studied and gained wide popularity due to their therapeutic potential. Spontaneous transformation of MSC, from both human and murine origin, has been reported in many studies. MSC transformation depends on the culture conditions, the origin of the cells and the time on culture; however, the precise biological characteristics involved in this process have not been fully defined yet. In this study, we investigated the role of p53 in the biology and transformation of murine bone marrow (BM)-derived MSC. We demonstrate that the MSC derived from p53KO mice showed an augmented proliferation rate, a shorter doubling time and also morphologic and phenotypic changes, as compared to MSC derived from wild-type animals. Furthermore, the MSC devoid of p53 had an increased number of cells able to generate colonies. In addition, not only proliferation but also MSC differentiation is controlled by p53 since its absence modifies the speed of the process. Moreover, genomic instability, changes in the expression of c-myc and anchorage independent growth were also observed in p53KO MSC. In addition, the absence of p53 implicates the spontaneous transformation of MSC in long-term cultures. Our results reveal that p53 plays a central role in the biology of MSC.

  11. 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.

  12. Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Handgretinger Rupert

    2010-01-01

    Full Text Available Abstract Background Human multipotent mesenchymal stromal cells (MSC can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity. Results After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1α expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation. Conclusion Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.

  13. Global phenotypic characterisation of human platelet lysate expanded MSCs by high-throughput flow cytometry.

    Science.gov (United States)

    Reis, Monica; McDonald, David; Nicholson, Lindsay; Godthardt, Kathrin; Knobel, Sebastian; Dickinson, Anne M; Filby, Andrew; Wang, Xiao-Nong

    2018-03-02

    Mesenchymal stromal cells (MSCs) are a promising cell source to develop cell therapy for many diseases. Human platelet lysate (PLT) is increasingly used as an alternative to foetal calf serum (FCS) for clinical-scale MSC production. To date, the global surface protein expression of PLT-expended MSCs (MSC-PLT) is not known. To investigate this, paired MSC-PLT and MSC-FCS were analysed in parallel using high-throughput flow cytometry for the expression of 356 cell surface proteins. MSC-PLT showed differential surface protein expression compared to their MSC-FCS counterpart. Higher percentage of positive cells was observed in MSC-PLT for 48 surface proteins, of which 13 were significantly enriched on MSC-PLT. This finding was validated using multiparameter flow cytometry and further confirmed by quantitative staining intensity analysis. The enriched surface proteins are relevant to increased proliferation and migration capacity, as well as enhanced chondrogenic and osteogenic differentiation properties. In silico network analysis revealed that these enriched surface proteins are involved in three distinct networks that are associated with inflammatory responses, carbohydrate metabolism and cellular motility. This is the first study reporting differential cell surface protein expression between MSC-PLT and MSC-FSC. Further studies are required to uncover the impact of those enriched proteins on biological functions of MSC-PLT.

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

    International Nuclear Information System (INIS)

    Inukai, Takeharu; Katagiri, Wataru; Yoshimi, Ryoko; Osugi, Masashi; Kawai, Takamasa; Hibi, Hideharu; Ueda, Minoru

    2013-01-01

    Highlights: ► Mesenchymal stem cells (MSCs) secrete a variety of cytokines. ► Cytokines were detected in conditioned medium from cultured MSCs (MSC-CM). ► MSC-CM enhanced activation of dog MSCs and periodontal ligament cells. ► MSC-CM significantly promoted alveolar bone and cementum regeneration. ► 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-β1, 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®) 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.

  15. The Life and Fate of Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Elke eEggenhofer

    2014-05-01

    Full Text Available Mesenchymal stem cells (MSC are present throughout the body and are thought to play a role in tissue regeneration and control of inflammation. MSC can be easily expanded in vitro and their potential as a therapeutic option for degenerative and inflammatory disease is therefore intensively investigated. Whilst it was initially thought that MSC would replace dysfunctional cells and migrate to sites of injury to interact with inflammatory cells, experimental evidence indicates that the majority of administered MSC get trapped in capillary networks and have a short life span. In this review we discuss current knowledge on the migratory properties of endogenous and exogenous MSC and confer on how culture induced modifications of MSC may affect these properties. Finally we will discuss how, despite their limited survival, administered MSC can bring about their therapeutic effects.

  16. Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells?

    Science.gov (United States)

    Zeddou, Mustapha; Relic, Biserka; Malaise, Michel G

    2014-01-01

    In cell therapy protocols, many tissues were proposed as a source of mesenchymal stem cells (MSC) isolation. So far, bone marrow (BM) has been presented as the main source of MSC despite the invasive isolation procedure related to this source. During the last years, the umbilical cord (UC) matrix was cited in different studies as a reliable source from which long term ex vivo proliferating fibroblasts were isolated but with contradictory data about their immunophenotype, gene expression profile, and differentiation potential. Hence, an interesting question emerged: Are cells isolated from cord matrix (UC-MSC) different from other MSCs? In this review, we will summarize different studies that isolated and characterized UC-MSC. Considering BM-MSC as gold standard, we will discuss if UC-MSC fulfill different criteria that define MSC, and what remain to be done in this issue. PMID:25126385

  17. 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 hMSC...... 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...... and adipocytes on the basis of gene expression and protein production of lineage-specific markers. In vivo, hMSC-CD146(+) and hMSC-CD146(-) cells formed bone and bone marrow organ when implanted subcutaneously in immune-deficient mice. Bone was enriched in hMSC-CD146(-) cells (12.6 % versus 8.1 %) and bone...

  18. Osteoblastic mesenchymal stem cell sheet combined with Choukroun platelet-rich fibrin induces bone formation at an ectopic site.

    Science.gov (United States)

    Wang, Zhifa; Weng, Yanming; Lu, Shengjun; Zong, Chunlin; Qiu, Jianyong; Liu, Yanpu; Liu, Bin

    2015-08-01

    To analyze the effects of platelet-rich fibrin (PRF) on mesenchymal stem cells (MSCs) in vitro and investigate in vivo bone formation by MSC sheets with PRF. Cell proliferation and expression of osteogenesis-related genes within MSC sheets were assessed upon exposure to PRF from the same donors. We then injected MSC sheet fragments with or without PRF subcutaneously in nude mice and assessed bone formation by micro-computed tomography and histological analyses. PRF significantly stimulated MSC proliferation and osteogenesis in vitro. MSC sheets injected with or without PRF formed new bone, but those with PRF produced significantly more and denser bone. MSC sheets can be used to generate tissue engineered bone upon injection, and PRF increases the osteogenic capacity of MSC sheets in vitro and in vivo. © 2014 Wiley Periodicals, Inc.

  19. Persistence of human parvovirus B19 in multipotent mesenchymal stromal cells expressing the erythrocyte P antigen: implications for transplantation

    Science.gov (United States)

    Sundin, Mikael; Lindblom, Anna; Örvell, Claes; Barrett, A.John; Sundberg, Berit; Watz, Emma; Wikman, Agneta; Broliden, Kristina; Le Blanc, Katarina

    2014-01-01

    Multipotent mesenchymal stromal cells (MSC) are used to improve the outcome of hematopoietic stem cell transplantation and in regenerative medicine. However, MSC may harbor persistent viruses that may compromise their clinical benefit. Retrospectively screened, 1 of 20 MSC from healthy donors contained parvovirus B19 (B19) DNA. We found that MSC express the B19 receptor (the globoside P antigen) and a co-receptor (Ku 80), and can transmit B19 to bone marrow cells in vitro, suggesting that the virus can persist in the marrow stroma of healthy individuals. Two stem cell transplant patients received the B19 positive MSC as treatment for graft-versus-host disease. Neither developed viremia nor symptomatic B19 infection. These results demonstrate for the first time that persistent B19 in MSC can infect hematopoietic cells and underscore the importance of monitoring B19 transmission by MSC products. PMID:18804048

  20. Proteomics reveals multiple routes to the osteogenic phenotype in mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Yener Bülent

    2007-10-01

    Full Text Available Abstract Background Recently, we demonstrated that human mesenchymal stem cells (hMSC stimulated with dexamethazone undergo gene focusing during osteogenic differentiation (Stem Cells Dev 14(6: 1608–20, 2005. Here, we examine the protein expression profiles of three additional populations of hMSC stimulated to undergo osteogenic differentiation via either contact with pro-osteogenic extracellular matrix (ECM proteins (collagen I, vitronectin, or laminin-5 or osteogenic media supplements (OS media. Specifically, we annotate these four protein expression profiles, as well as profiles from naïve hMSC and differentiated human osteoblasts (hOST, with known gene ontologies and analyze them as a tensor with modes for the expressed proteins, gene ontologies, and stimulants. Results Direct component analysis in the gene ontology space identifies three components that account for 90% of the variance between hMSC, osteoblasts, and the four stimulated hMSC populations. The directed component maps the differentiation stages of the stimulated stem cell populations along the differentiation axis created by the difference in the expression profiles of hMSC and hOST. Surprisingly, hMSC treated with ECM proteins lie closer to osteoblasts than do hMSC treated with OS media. Additionally, the second component demonstrates that proteomic profiles of collagen I- and vitronectin-stimulated hMSC are distinct from those of OS-stimulated cells. A three-mode tensor analysis reveals additional focus proteins critical for characterizing the phenotypic variations between naïve hMSC, partially differentiated hMSC, and hOST. Conclusion The differences between the proteomic profiles of OS-stimulated hMSC and ECM-hMSC characterize different transitional phenotypes en route to becoming osteoblasts. This conclusion is arrived at via a three-mode tensor analysis validated using hMSC plated on laminin-5.

  1. Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal tissue regeneration.

    Science.gov (United States)

    Kawai, Takamasa; Katagiri, Wataru; Osugi, Masashi; Sugimura, Yukiko; Hibi, Hideharu; Ueda, Minoru

    2015-04-01

    Periodontal tissue regeneration with the use of mesenchymal stromal cells (MSCs) has been regarded as a future cell-based therapy. However, low survival rates and the potential tumorigenicity of implanted MSCs could undermine the efficacy of cell-based therapy. The use of conditioned media from MSCs (MSC-CM) may be a feasible approach to overcome these limitations. The aim of this study was to confirm the effect of MSC-CM on periodontal regeneration. MSC-CM were collected during their cultivation. The concentrations of the growth factors in MSC-CM were measured with the use of enzyme-linked immunoassay. Rat MSCs (rMSCs) and human umbilical vein endothelial cells cultured in MSC-CM were assessed on wound-healing and angiogenesis. The expressions of osteogenetic- and angiogenic-related genes of rMSCs cultured in MSC-CM were quantified by means of real-time reverse transcriptase-polymerase chain reaction analysis. In vivo, periodontal defects were prepared in the rat models and the collagen sponges with MSC-CM were implanted. MSC-CM includes insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-β1 and hepatocyte growth factor. In vitro, wound-healing and angiogenesis increased significantly in MSC-CM. The levels of expression of osteogenetic- and angiogenic-related genes were significantly upregulated in rMSCs cultured with MSC-CM. In vivo, in the MSC-CM group, 2 weeks after implantation, immunohistochemical analysis showed several CD31-, CD105-or FLK-1-positive cells occurring frequently. At 4 weeks after implantation, regenerated periodontal tissue was observed in MSC-CM groups. The use of MSC-CM may be an alternative therapy for periodontal tissue regeneration because several cytokines included in MSC-CM will contribute to many processes of complicated periodontal tissue regeneration. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  2. Antimicrobial peptides secreted by equine mesenchymal stromal cells inhibit the growth of bacteria commonly found in skin wounds.

    Science.gov (United States)

    Harman, Rebecca M; Yang, Steven; He, Megan K; Van de Walle, Gerlinde R

    2017-07-04

    The prevalence of chronic skin wounds in humans is high, and treatment is often complicated by the presence of pathogenic bacteria. Therefore, safe and innovative treatments to reduce the bacterial load in cutaneous wounds are needed. Mesenchymal stromal cells (MSC) are known to provide paracrine signals that act on resident skin cells to promote wound healing, but their potential antibacterial activities are not well described. The present study was designed to examine the antibacterial properties of MSC from horses, as this animal model offers a readily translatable model for MSC therapies in humans. Specifically, we aimed to (i) evaluate the in vitro effects of equine MSC on the growth of representative gram-negative and gram-positive bacterial species commonly found in skin wounds and (ii) define the mechanisms by which MSC inhibit bacterial growth. MSC were isolated from the peripheral blood of healthy horses. Gram-negative E. coli and gram-positive S. aureus were cultured in the presence of MSC and MSC conditioned medium (CM), containing all factors secreted by MSC. Bacterial growth was measured by plating bacteria and counting viable colonies or by reading the absorbance of bacterial cultures. Bacterial membrane damage was detected by incorporation of N-phenyl-1-naphthylamine (NPN). Antimicrobial peptide (AMP) gene and protein expression by equine MSC were determined by RT-PCR and Western blot analysis, respectively. Blocking of AMP activity of MSC CM was achieved using AMP-specific antibodies. We found that equine MSC and MSC CM inhibit the growth of E. coli and S. aureus, and that MSC CM depolarizes the cell membranes of these bacteria. In addition, we found that equine MSC CM contains AMPs, and blocking these AMPs with antibodies reduces the effects of MSC CM on bacteria. Our results demonstrate that equine MSC inhibit bacterial growth and secrete factors that compromise the membrane integrity of bacteria commonly found in skin wounds. We also identified

  3. GAC-EPA

    CERN Multimedia

    GAC-EPA

    2012-01-01

    Alzheimer Association Switzerland Wednesday, 29th February 2012 - From 6 pm to 8 pm Hotel Mandarin Oriental - Quai Turrettini 1 - Geneva A public conference in English about   Alzheimer’s disease and other dementias   Prof. Dr Gabriel GOLD, Head of the Division of Geriatrics at Geneva University Hospital, will talk about medical topics related to Alzheimer’s disease and other dementias. Elizabeth BOHLER-GOODSHIP, Mayor of Grand-Saconnex and Vice-president of Alzheimer Geneva, will present the section’s services for English-speaking people in the Geneva area. Birgitta MARTENSSON, Executive Director of Alzheimer Switzerland, will highlight some facts and figures about dementia in Switzerland. Drinks and snacks will be served after the presentations, giving the audience the opportunity to talk with the speakers and other members of the Association. Entrance free To help us organize the event, please announce your participation to sophie.courvoisier@a...

  4. Plasmid-based genetic modification of human bone marrow-derived stromal cells: analysis of cell survival and transgene expression after transplantation in rat spinal cord.

    Science.gov (United States)

    Ronsyn, Mark W; Daans, Jasmijn; Spaepen, Gie; Chatterjee, Shyama; Vermeulen, Katrien; D'Haese, Patrick; Van Tendeloo, Viggo Fi; Van Marck, Eric; Ysebaert, Dirk; Berneman, Zwi N; Jorens, Philippe G; Ponsaerts, Peter

    2007-12-14

    Bone marrow-derived stromal cells (MSC) are attractive targets for ex vivo cell and gene therapy. In this context, we investigated the feasibility of a plasmid-based strategy for genetic modification of human (h)MSC with enhanced green fluorescent protein (EGFP) and neurotrophin (NT)3. Three genetically modified hMSC lines (EGFP, NT3, NT3-EGFP) were established and used to study cell survival and transgene expression following transplantation in rat spinal cord. First, we demonstrate long-term survival of transplanted hMSC-EGFP cells in rat spinal cord under, but not without, appropriate immune suppression. Next, we examined the stability of EGFP or NT3 transgene expression following transplantation of hMSC-EGFP, hMSC-NT3 and hMSC-NT3-EGFP in rat spinal cord. While in vivo EGFP mRNA and protein expression by transplanted hMSC-EGFP cells was readily detectable at different time points post-transplantation, in vivo NT3 mRNA expression by hMSC-NT3 cells and in vivo EGFP protein expression by hMSC-NT3-EGFP cells was, respectively, undetectable or declined rapidly between day 1 and 7 post-transplantation. Further investigation revealed that the observed in vivo decline of EGFP protein expression by hMSC-NT3-EGFP cells: (i) was associated with a decrease in transgenic NT3-EGFP mRNA expression as suggested following laser capture micro-dissection analysis of hMSC-NT3-EGFP cell transplants at day 1 and day 7 post-transplantation, (ii) did not occur when hMSC-NT3-EGFP cells were transplanted subcutaneously, and (iii) was reversed upon re-establishment of hMSC-NT3-EGFP cell cultures at 2 weeks post-transplantation. Finally, because we observed a slowly progressing tumour growth following transplantation of all our hMSC cell transplants, we here demonstrate that omitting immune suppressive therapy is sufficient to prevent further tumour growth and to eradicate malignant xenogeneic cell transplants. In this study, we demonstrate that genetically modified hMSC lines can survive

  5. Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

    Science.gov (United States)

    Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Renée; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle; Beauséjour, Christian; Stroncek, David; Le Deist, Françoise; Haddad, Elie

    2016-01-01

    Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation. PMID:27070086

  6. Safety and immune regulatory properties of canine induced pluripotent stem cell-derived mesenchymal stem cells.

    Science.gov (United States)

    Chow, Lyndah; Johnson, Valerie; Regan, Dan; Wheat, William; Webb, Saiphone; Koch, Peter; Dow, Steven

    2017-12-01

    Mesenchymal stem cells (MSCs) exhibit broad immune modulatory activity in vivo and can suppress T cell proliferation and dendritic cell activation in vitro. Currently, most MSC for clinical usage are derived from younger donors, due to ease of procurement and to the superior immune modulatory activity. However, the use of MSC from multiple unrelated donors makes it difficult to standardize study results and compare outcomes between different clinical trials. One solution is the use of MSC derived from induced pluripotent stem cells (iPSC); as iPSC-derived MSC have nearly unlimited proliferative potential and exhibit in vitro phenotypic stability. Given the value of dogs as a spontaneous disease model for pre-clinical evaluation of stem cell therapeutics, we investigated the functional properties of canine iPSC-derived MSC (iMSC), including immune modulatory properties and potential for teratoma formation. We found that canine iMSC downregulated expression of pluripotency genes and appeared morphologically similar to conventional MSC. Importantly, iMSC retained a stable phenotype after multiple passages, did not form teratomas in immune deficient mice, and did not induce tumor formation in dogs following systemic injection. We concluded therefore that iMSC were phenotypically stable, immunologically potent, safe with respect to tumor formation, and represented an important new source of cells for therapeutic modulation of inflammatory disorders. Copyright © 2017. Published by Elsevier B.V.

  7. Estrogenic effects of marijuana smoke condensate and cannabinoid compounds

    International Nuclear Information System (INIS)

    Lee, Soo Yeun; Oh, Seung Min; Chung, Kyu Hyuck

    2006-01-01

    Chronic exposure to marijuana produces adverse effects on the endocrine and reproductive systems in humans; however, the experimental evidence for this presented thus far has not been without controversy. In this study, the estrogenic effect of marijuana smoke condensate (MSC) was evaluated using in vitro bioassays, viz., the cell proliferation assay, the reporter gene assay, and the ER competitive binding assay. The results of these assays were compared with those of three major cannabinoids, i.e., THC, CBD, and CBN. The estrogenic effect of MSC was further confirmed by the immature female rat uterotrophic assay. MSC stimulated the estrogenicity related to the ER-mediated pathway, while neither THC, CBD, nor CBN did. Moreover, treatment with 10 and 25 mg/kg MSC induced significant uterine response, and 10 mg/kg MSC resulted in an obvious change in the uterine epithelial cell appearance. MSC also enhanced the IGFBP-1 gene expression in a dose-dependent manner. To identify the constituents of MSC responsible for its estrogenicity, the MSC fractionated samples were examined using another cell proliferation assay, and the estrogenic active fraction was analyzed using GC-MS. In the organic acid fraction that showed the strongest estrogenic activity among the seven fractions of MSC, phenols were identified. Our results suggest that marijuana abuse is considered an endocrine-disrupting factor. Furthermore, these results suggest that the phenolic compounds contained in MSC play a role in its estrogenic effect

  8. Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses.

    Science.gov (United States)

    Pigott, J H; Ishihara, A; Wellman, M L; Russell, D S; Bertone, A L

    2013-01-01

    To compare the clinical and inflammatory joint responses to intra-articular injection of bone marrow-derived mesenchymal stem cells (MSC) including autologous, genetically modified autologous, allogeneic, or xenogeneic cells in horses. Six five-year-old Thoroughbred mares had one fetlock joint injected with Gey's balanced salt solution as the vehicle control. Each fetlock joint of each horse was subsequently injected with 15 million MSC from the described MSC groups, and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, joint swelling, and pain. There were not any significant differences between autologous and genetically modified autologous MSC for synovial fluid total nucleated cell count, total protein, interleukin (IL)-6, IL-10, fetlock circumference, oedema score, pain-free range-of-motion, and soluble gene products that were detected for at least two days. Allogeneic and xenogeneic MSC produced a greater increase in peak of inflammation at 24 hours than either autologous MSC group. Genetically engineered MSC can act as vehicles to deliver gene products to the joint; further investigation into the therapeutic potential of this cell therapy is warranted. Intra-articular MSC injection resulted in a moderate acute inflammatory joint response that was greater for allogeneic and xenogeneic MSC than autologous MSC. Clinical management of this response may minimize this effect.

  9. Reduced reactivation from dormancy but maintained lineage choice of human mesenchymal stem cells with donor age.

    Directory of Open Access Journals (Sweden)

    Verena Dexheimer

    Full Text Available UNLABELLED: Mesenchymal stem cells (MSC are promising for cell-based regeneration therapies but up to date it is still controversial whether their function is maintained throughout ageing. Aim of this study was to address whether frequency, activation in vitro, replicative function, and in vitro lineage choice of MSC is maintained throughout ageing to answer the question whether MSC-based regeneration strategies should be restricted to younger individuals. MSC from bone marrow aspirates of 28 donors (5-80 years were characterized regarding colony-forming unit-fibroblast (CFU-F numbers, single cell cloning efficiency (SSCE, osteogenic, adipogenic and chondrogenic differentiation capacity in vitro. Alkaline phosphatase (ALP activity, mineralization, Oil Red O content, proteoglycan- and collagen type II deposition were quantified. While CFU-F frequency was maintained, SSCE and early proliferation rate decreased significantly with advanced donor age. MSC with higher proliferation rate before start of induction showed stronger osteogenic, adipogenic and chondrogenic differentiation. MSC with high osteogenic capacity underwent better chondrogenesis and showed a trend to better adipogenesis. Lineage choice was, however, unaltered with age. CONCLUSION: Ageing influenced activation from dormancy and replicative function of MSC in a way that it may be more demanding to mobilize MSC to fast cell growth at advanced age. Since fast proliferation came along with high multilineage capacity, the proliferation status of expanded MSC rather than donor age may provide an argument to restrict MSC-based therapies to certain individuals.

  10. Zero-valent iron particles embedded on the mesoporous silica–carbon for chromium (VI) removal from aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Kun, E-mail: kunxiong312@gmail.com; Gao, Yuan [Chongqing Technology and Business University, Engineering Research Center for Waste Oil Recovery Technology and Equipment of Ministry of Education, Chongqing Key Laboratory of Catalysis & Environmental New Materials (China); Zhou, Lin [Chengdu Radio and TV University (China); Zhang, Xianming [Chongqing Technology and Business University, Engineering Research Center for Waste Oil Recovery Technology and Equipment of Ministry of Education, Chongqing Key Laboratory of Catalysis & Environmental New Materials (China)

    2016-09-15

    Nanoscale zero-valent iron (nZVI) particles were embedded on the walls of mesoporous silica–carbon (MSC) under the conditions of high-temperature carbonization and reduction and used to remove chromium (VI) from aqueous solution. The structure and textural properties of nZVI–MSC were characterized by the powder X-ray diffraction, transmission electron microscopy and N{sub 2} adsorption and desorption. The results show that nZVI–MSC has highly ordered mesoporous structure and large surface area, indistinguishable with that of MSC. Compared with the support MSC and iron particles supported on the activated carbon (nZVI/AC), nZVI–MSC exhibited much higher Cr(VI) removal efficiency with about 98 %. The removal process obeys a pseudo first-order model. Such excellent performance of nZVI–MSC could be ascribed to the large surface and iron particles embedded on the walls of the MSC, forming an intimate contact with the MSC. It is proposed that this feature might create certain micro-electrode on the interface of iron particles and MSC, which prevented the formation of metal oxide on the surface and provided fresh Fe surface for Cr(VI) removal.

  11. 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.

  12. DSP30 enhances the immunosuppressive properties of mesenchymal stromal cells and protects their suppressive potential from lipopolysaccharide effects: A potential role of adenosine.

    Science.gov (United States)

    Sangiorgi, Bruno; De Freitas, Helder Teixeira; Schiavinato, Josiane Lilian Dos Santos; Leão, Vitor; Haddad, Rodrigo; Orellana, Maristela Delgado; Faça, Vitor Marcel; Ferreira, Germano Aguiar; Covas, Dimas Tadeu; Zago, Marco Antônio; Panepucci, Rodrigo Alexandre

    2016-07-01

    Multipotent mesenchymal stromal cells (MSC) are imbued with an immunosuppressive phenotype that extends to several immune system cells. In this study, we evaluated how distinct Toll-like receptor (TLR) agonists impact immunosuppressive properties of bone marrow (BM)-MSC and explored the potential mechanisms involved. We show that TLR4 stimulation by lipopolysaccharide (LPS) restricted the ability of MSC to suppress the proliferation of T lymphocytes, increasing the gene expression of interleukin (IL)-1β and IL-6. In contrast, stimulation of TLR9 by DSP30 induced proliferation and the suppressive potential of BM-MSC, coinciding with reducing tumor necrosis factor (TNF)-α expression, increased expression of transforming growth factor (TGF)-β1, increased percentages of BM-MSC double positive for the ectonucleotidases CD39+CD73+ and adenosine levels. Importantly, following simultaneous stimulation with LPS and DSP30, BM-MSC's ability to suppress T lymphocyte proliferation was comparable with that of non-stimulated BM-MSC levels. Moreover, stimulation of BM-MSC with LPS reduced significantly the gene expression levels, on co-cultured T lymphocyte, of IL-10 and interferon (IFN)γ, a cytokine with potential to enhance the immunosuppression mediated by MSC and ameliorate the clinical outcome of patients with graft-versus-host disease (GVHD). Altogether, our findings reiterate the harmful effects of LPS on MSC immunosuppression, besides indicating that DSP30 could provide a protective effect against LPS circulating in the blood of GVHD patients who receive BM-MSC infusions, ensuring a more predictable immunosuppressive effect. The novel effects and potential mechanisms following the stimulation of BM-MSC by DSP30 might impact their clinical use, by allowing the derivation of optimal "licensing" protocols for obtaining therapeutically efficient MSC. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  13. 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.

  14. Bone marrow mesenchymal stem cells for improving hematopoietic function: an in vitro and in vivo model. Part 2: Effect on bone marrow microenvironment.

    Directory of Open Access Journals (Sweden)

    Soraya Carrancio

    Full Text Available The aim of the present study was to determine how mesenchymal stem cells (MSC could improve bone marrow (BM stroma function after damage, both in vitro and in vivo. Human MSC from 20 healthy donors were isolated and expanded. Mobilized selected CD34(+ progenitor cells were obtained from 20 HSCT donors. For in vitro study, long-term bone marrow cultures (LTBMC were performed using a etoposide damaged stromal model to test MSC effect in stromal confluence, capability of MSC to lodge in stromal layer as well as some molecules (SDF1, osteopontin, involved in hematopoietic niche maintenance were analyzed. For the in vivo model, 64 NOD/SCID recipients were transplanted with CD34+ cells administered either by intravenous (i.v. or intrabone (i.b. route, with or without BM derived MSC. MSC lodgement within the BM niche was assessed by FISH analysis and the expression of SDF1 and osteopontin by immunohistochemistry. In vivo study showed that when the stromal damage was severe, TP-MSC could lodge in the etoposide-treated BM stroma, as shown by FISH analysis. Osteopontin and SDF1 were differently expressed in damaged stroma and their expression restored after TP-MSC addition. Human in vivo MSC lodgement was observed within BM niche by FISH, but MSC only were detected and not in the contralateral femurs. Human MSC were located around blood vessels in the subendoestal region of femurs and expressed SDF1 and osteopontin. In summary, our data show that MSC can restore BM stromal function and also engraft when a higher stromal damage was done. Interestingly, MSC were detected locally where they were administered but not in the contralateral femur.

  15. Aspectos sociopsicológicos del medio laboral asociados a la autoestima de personas que viven con VIHn Notificaciones Ver (159 Administrar  Contenido de la revista Herramientas del artículo Imprimir este artículo Metadatos de indexación Cómo citar un elemento Publicar un comentario Información Para los lectores/as Para los autores/as Para los bibliotecarios/as Acerca de los autores/as Lic. Nielvis de la Caridad Senra Pérez MSc. Mailé Contrera Betarte MSc. Yexenia Martín Chávez Encuéntranos en... Inicio / Aspectos sociopsicológicos del medio laboral asociados a la autoestima de personas que viven con VIH

    Directory of Open Access Journals (Sweden)

    Lic. Nielvis de la Caridad Senra Pérez

    2016-06-01

    Full Text Available La presente investigación consiste en un estudio cuali-cuantitativo, no experimental, que comienza siendo descriptivo y continúa siendo correlacional, describiendo y relacionando las variables: autoestima, apoyo social y conocimiento que poseen los directivos y trabajadores sobre el Virus de Inmunodeficiencia Humana. Persiguiendo como objetivo determinar la posible asociación entre los aspectos sociopsicológicos del medio laboral con la autoestima de las personas que viven con el virus. Para la realización del mismo se emplean métodos del nivel teórico, empírico y estadístico. La selección de la muestra se hace coincidir con el universo (todas las personas de Rodas que viven con el Virus de Inmunodeficiencia Humana, que se encuentran laborando por ser este uno de los municipios que más casos aporta en la provincia de Cienfuegos. Se emplean diferentes técnicas para la recogida de datos como son: entrevista en profundidad, semiestructurada, observación participante, cuestionario de apoyo social e inventario de autoestima de Coopersmith. Los resultados se muestran en tablas y figuras, así como se hace un análisis porcentual y se realiza la valoración estadística mediante la correlación de Spearman.

  16. Pathogen-free, plasma-poor platelet lysate and expansion of human mesenchymal stem cells.

    Science.gov (United States)

    Iudicone, Paola; Fioravanti, Daniela; Bonanno, Giuseppina; Miceli, Michelina; Lavorino, Claudio; Totta, Pierangela; Frati, Luigi; Nuti, Marianna; Pierelli, Luca

    2014-01-27

    Supplements to support clinical-grade cultures of mesenchymal stem cells (MSC) are required to promote growth and expansion of these cells. Platelet lysate (PL) is a human blood component which may replace animal serum in MSC cultures being rich in various growth factors. Here, we describe a plasma poor pathogen-free platelet lysate obtained by pooling 12 platelet (PLT) units, to produce a standardized and safe supplement for clinical-grade expansion of MSC. PL lots were obtained by combining 2 6-unit PLT pools in additive solution (AS) following a transfusional-based procedure including pathogen inactivation (PI) by Intercept technology and 3 cycles of freezing/thawing, followed by membrane removal. Three PI-PL and 3 control PL lots were produced to compare their ability to sustain bone marrow derived MSC selection and expansion. Moreover, two further PL, subjected to PI or not, were also produced starting from the same initial PLT pools to evaluate the impact of PI on growth factor concentration and capacity to sustain cell growth. Additional PI-PL lots were used for comparison with fetal bovine serum (FBS) on MSC expansion. Immunoregulatory properties of PI-PL-generated MSC were documented in vitro by mixed lymphocyte culture (MLC) and peripheral blood mononuclear cells (PBMC) mitogen induced proliferation. PI-PL and PL control lots had similar concentrations of 4 well-described growth factors endowed with MSC stimulating ability. Initial growth and MSC expansion by PI-PL and PL controls were comparable either using different MSC populations or in head to head experiments. Moreover, PI-PL and PL control sustained similar MSC growth of frozen/thawed MSC. Multilineage differentiation of PI-derived and PI-PL-derived MSC were maintained in any MSC cultures as well as their immunoregulatory properties. Finally, no direct impact of PI on growth factor concentration and MSC growth support was observed, whereas the capacity of FBS to sustain MSC expansion in basic

  17. Aging of bone marrow mesenchymal stromal/stem cells: Implications on autologous regenerative medicine.

    Science.gov (United States)

    Charif, N; Li, Y Y; Targa, L; Zhang, L; Ye, J S; Li, Y P; Stoltz, J F; Han, H Z; de Isla, N

    2017-01-01

    With their proliferation, differentiation into specific cell types, and secretion properties, mesenchymal stromal/stem cells (MSC) are very interesting tools to be used in regenerative medicine. Bone marrow (BM) was the first MSC source characterized. In the frame of autologous MSC therapy, it is important to detect donor's parameters affecting MSC potency. Age of the donors appears as one parameter that could greatly affect MSC properties. Moreover, in vitro cell expansion is needed to obtain the number of cells necessary for clinical developments. It will lead to in vitro cell aging that could modify cell properties. This review recapitulates several studies evaluating the effect of in vitro and in vivo MSC aging on cell properties.

  18. Lignin-rich biomass of cotton by-products for biorefineries via pyrolysis.

    Science.gov (United States)

    Chen, Jiao; Liang, Jiajin; Wu, Shubin

    2016-10-01

    Pyrolysis was demonstrated to investigate the thermal decomposition characteristics and potential of lignin-rich cotton by-products cotton exocarp (CE) and spent mushroom substrate consisted of cotton by-products (MSC) for biorefineries. The chemical component and structure alteration of CE and MSC was found to affect their thermochemical behaviors. The bio-oil yield from CE was 58.13wt% while the maximum yield from MSC was 45.01% at 600°C. The phenolic compounds obtained from CE and MSC were 33.9% and 39.2%, respectively. The yield of acetic acid from MSC between 400 and 600°C was about 30-38% lower than that from CE, which suggests the high quality of bio-oil was obtained. Biochar from MSC via slow pyrolysis had a high mass yield (44.38wt%) with well-developed pore structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. 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

    Regenerative medicine is a novel approach for treating conditions in which enhanced bone regeneration is required. We identified transgelin (TAGLN), a transforming growth factor beta (TGFβ)-inducible gene, as an upregulated gene during in vitro osteoblastic and adipocytic differentiation of human......MSC by regulating cytoskeleton organization. Targeting TAGLN is a plausible approach to enrich for committed hMSC cells needed for regenerative medicine application....... 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...

  20. Alignment of Malaysia and ASEAN Agreements on Ict Laws: a Review

    OpenAIRE

    Manap, Nazura Abdul

    2015-01-01

    The mega Multimedia Super Corridor (MSC) project launched in 1996 is a strong endorsement of the Malaysian government's commitment towards developing the ICT industry in Malaysia. To attract world-class technology companies and prepare the local ICT industry, the government has offered MSC Malaysia Status to companies developing or using multimedia technologies in producing and enhancing their products and services and locating in any of the 26 Cybercities and Cyber centres in Malaysia. MSC s...

  1. Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

    OpenAIRE

    Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen; Wang, Fu-Sheng

    2012-01-01

    This study assessed the safety and initial efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) transfusions for acute-on-chronic liver failure (ACLF) patients associated with hepatitis B virus (HBV) infection. No significant side effects were observed, and the UC-MSC transfusions significantly increased the survival rates in ACLF patients. It was found that UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients.

  2. The application of coloured Petri nets to verification of distributed systems specified by message Sequence Charts

    OpenAIRE

    CHERNENOK S.A.; NEPOMNIASCHY V.A.

    2015-01-01

    The language of message sequence charts (MSC) is a popular scenario-based specification language used to describe the interaction of components in distributed systems. However, the methods for validation of MSC diagrams are underdeveloped. This paper describes a method for translation of MSC diagrams into coloured Petri nets (CPN). The method is applied to the property verification of these diagrams. The considered set of diagram elements is extended by the elements of UML sequence diagrams a...

  3. Society of Archaeological Masters Students Annual Conference V

    Directory of Open Access Journals (Sweden)

    Nicole Barber

    2017-10-01

    Full Text Available The Society of Archaeological Masters Students Conference is an opportunity for UCL Institute of Archaeology masters students to present their research. This year’s conference included papers from MA Cultural Heritage Studies, MSc Bioarchaeology and Forensic Anthropology, MSc Archaeological Science: Technology and Materials, and MSc Palaeoanthropology and Palaeolithic Archaeology students. The event sparked discussion between students from all areas of the department, and showcased the impressive range of research currently undertaken at the Institute of Archaeology.

  4. Acceleration of wound healing with stem cell-derived growth factors.

    Science.gov (United States)

    Tamari, Masayuki; Nishino, Yudai; Yamamoto, Noriyuki; Ueda, Minoru

    2013-01-01

    Recently, it has been revealed that bone marrow-derived mesenchymal stem cells (MSCs) accelerate the healing of skin wounds. Although the proliferative capacity of MSCs decreases with age, MSCs secrete many growth factors. The present study examined the effect of mesenchymal stem cell-conditioned medium (MSC-CM) on wound healing. The wound-healing process was observed macroscopically and histologically using an excisional wound-splinting mouse model, and the expression level of hyaluronic acid related to the wound healing process was observed to evaluate the wound-healing effects of MSC, MSC-CM, and control (phosphate-buffered saline). The MSC and MSC-CM treatments accelerated wound healing versus the control group. At 7 days after administration, epithelialization was accelerated, thick connective tissue had formed in the skin defect area, and the wound area was reduced in the MSC and MSC-CM groups versus the control group. At 14 days, infiltration of inflammatory cells was decreased versus 7 days, and the wounds were closed in the MSC and MSC-CM groups, while a portion of epithelium was observed in the control group. At 7 and 14 days, the MSC and MSC-CM groups expressed significantly higher levels of hyaluronic acid versus the control group (P wound healing versus the control group to a similar degree. Accordingly, it is suggested that the MSC-CM contains growth factor derived from stem cells, is able to accelerate wound healing as well as stem cell transplantation, and may become a new therapeutic method for wound healing in the future.

  5. Hypoxic Preconditioning Promotes the Bioactivities of Mesenchymal Stem Cells via the HIF-1?-GRP78-Akt Axis

    OpenAIRE

    Lee, Jun Hee; Yoon, Yeo Min; Lee, Sang Hun

    2017-01-01

    Mesenchymal stem cells (MSC) are ideal materials for stem cell-based therapy. As MSCs reside in hypoxic microenvironments (low oxygen tension of 1% to 7%), several studies have focused on the beneficial effects of hypoxic preconditioning on MSC survival; however, the mechanisms underlying such effects remain unclear. This study aimed to uncover the potential mechanism involving 78-kDa glucose-regulated protein (GRP78) to explain the enhanced MSC bioactivity and survival in hindlimb ischemia. ...

  6. Hepatoma SK Hep-1 cells exhibit characteristics of oncogenic mesenchymal stem cells with highly metastatic capacity.

    Directory of Open Access Journals (Sweden)

    Jong Ryeol Eun

    Full Text Available SK Hep-1 cells (SK cells derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here, we characterized SK cells and its tumourigenicity.We found that classical mesenchymal stem cell (MSC markers were presented on SK cells, but endothelial marker CD31, hematopoietic markers CD34 and CD45 were negative. SK cells are capable of differentiate into adipocytes and osteoblasts as adipose-derived MSC (Ad-MSC and bone marrow-derived MSC (BM-MSC do. Importantly, a single SK cell exhibited a substantial tumourigenicity and metastatic capacity in immunodefficient mice. Metastasis not only occurred in circulating organs such as lung, liver, and kidneys, but also in muscle, outer abdomen, and skin. SK cells presented greater in vitro invasive capacity than those of Ad-MSC and BM-MSC. The xenograft cells from subcutaneous and metastatic tumors exhibited a similar tumourigenicity and metastatic capacity, and showed the same relatively homogenous population with MSC characteristics when compared to parental SK cells. SK cells could unlimitedly expand in vitro without losing MSC characteristics, its tumuorigenicity and metastatic capacity, indicating that SK cells are oncogenic MSC with enhanced self-renewal capacity. We believe that this is the first report that human MSC appear to be transformed into cancer stem cells (CSC, and that their derivatives also function as CSCs.Our findings demonstrate that SK cells represent a transformation mechanism of normal MSC into an enhanced self-renewal CSC with metastasis capacity, SK cells and their xenografts represent a same relative homogeneity of CSC with substantial metastatic capacity. Thus, it represents a novel mechanism of tumor initiation, development and

  7. Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

    DEFF Research Database (Denmark)

    Rolandsson, Sara; Andersson Sjöland, Annika; Brune, Jan C

    2014-01-01

    BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This st......BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported...

  8. Master sintering curve: A practical approach to its construction

    Directory of Open Access Journals (Sweden)

    Pouchly V.

    2010-01-01

    Full Text Available The concept of a Master Sintering Curve (MSC is a strong tool for optimizing the sintering process. However, constructing the MSC from sintering data involves complicated and time-consuming calculations. A practical method for the construction of a MSC is presented in the paper. With the help of a few dilatometric sintering experiments the newly developed software calculates the MSC and finds the optimal activation energy of a given material. The software, which also enables sintering prediction, was verified by sintering tetragonal and cubic zirconia, and alumina of two different particle sizes.

  9. ANAM4 TBI Reaction Time-Based Tests have Prognostic Utility for Acute Concussion

    Science.gov (United States)

    2013-07-01

    7:767. 2013 ANAM4 TBI Reaction Time-Based Tests Have Prognostic Utility for Acute Concussion LT Jacob N. Norris, MSC USN*; LCDR Waiter Carr, MSC USN...CDR Thomas Herzig, MSC USNf; CDR D. Waiter Labrie, MSC USNf; CDR Richard Sams, MC USN§ ABSTRACT The Concussion Restoration Care Center has used the...Work Unit No. N24LB. REFERENCES 1. Department of Defense: DoD Poiicy Guidance for Management of Mild Traumatic Brain Injury/Concussion in the Deployed

  10. Human umbilical cord mesenchymal stem cells increase interleukin-9 production of CD4+ T cells

    OpenAIRE

    Yang, Zhou Xin; Chi, Ying; Ji, Yue Ru; Wang, You Wei; Zhang, Jing; Luo, Wei Feng; Li, Li Na; Hu, Cai Dong; Zhuo, Guang Sheng; Wang, Li Fang; Han, Zhi-Bo; Han, Zhong Chao

    2017-01-01

    Mesenchymal stem cells (MSC) are able to differentiate into cells of multiple lineage, and additionally act to modulate the immune response. Interleukin (IL)-9 is primarily produced by cluster of differentiation (CD)4+ T cells to regulate the immune response. The present study aimed to investigate the effect of human umbilical cord derived-MSC (UC-MSC) on IL-9 production of human CD4+ T cells. It was demonstrated that the addition of UC-MSC to the culture of CD4+ T cells significantly enhance...

  11. Human umbilical cord mesenchymal stem cells increase interleukin-9 production of CD4+ T cells

    Science.gov (United States)

    Yang, Zhou Xin; Chi, Ying; Ji, Yue Ru; Wang, You Wei; Zhang, Jing; Luo, Wei Feng; Li, Li Na; Hu, Cai Dong; Zhuo, Guang Sheng; Wang, Li Fang; Han, Zhi-Bo; Han, Zhong Chao

    2017-01-01

    Mesenchymal stem cells (MSC) are able to differentiate into cells of multiple lineage, and additionally act to modulate the immune response. Interleukin (IL)-9 is primarily produced by cluster of differentiation (CD)4+ T cells to regulate the immune response. The present study aimed to investigate the effect of human umbilical cord derived-MSC (UC-MSC) on IL-9 production of human CD4+ T cells. It was demonstrated that the addition of UC-MSC to the culture of CD4+ T cells significantly enhanced IL-9 production by CD4+ T cells. Transwell experiments suggested that UC-MSC promotion of IL-9 production by CD4+ T cells was dependent on cell-cell contact. Upregulated expression of CD106 was observed in UC-MSC co-cultured with CD4+ T cells, and the addition of a blocking antibody of CD106 significantly impaired the ability of UC-MSC to promote IL-9 production by CD4+ T cells. Therefore, the results of the present study demonstrated that UC-MSC promoted the generation of IL-9 producing cells, which may be mediated, in part by CD106. The findings may act to expand understanding and knowledge of the immune modulatory role of UC-MSC. PMID:29042945

  12. Robust Analysis and Prediction for Integrated Design of Structures (RAPIDS), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Commercially available software suites such as the Automate Structural Optimization System (ASTROS) and MSC/NASTRAN represent the current industry standard in...

  13. Mesenchymal stem cell-conditioned medium prevents radiation-induced liver injury by inhibiting inflammation and protecting sinusoidal endothelial cells

    International Nuclear Information System (INIS)

    Chen Yixing; Zeng Zhaochong; Sun Jing; Huang Yan; Zhang Zhenyu; Zeng Haiying

    2015-01-01

    Current management of radiation-induced liver injury is limited. Sinusoidal endothelial cell (SEC) apoptosis and inflammation are considered to be initiating events in hepatic damage. We hypothesized that mesenchymal stem cells (MSCs) possess anti-apoptotic and anti-inflammatory actions during hepatic irradiation, acting via paracrine mechanisms. This study aims to examine whether MSC-derived bioactive components are protective against radiation-induced liver injury in rats. MSC-conditioned medium (MSC-CM) was generated from rat bone marrow–derived MSCs. The effect of MSC-CM on the viability of irradiated SECs was examined by flow cytometric analysis. Activation of the Akt and ERK pathways was analyzed by western blot. MSC-CM was also delivered to Sprague–Dawley rats immediately before receiving liver irradiation, followed by testing for pathological features, changes in serum hyaluronic acid, ALT, and inflammatory cytokine levels, and liver cell apoptosis. MSC-CM enhanced the viability of irradiated SECs in vitro and induced Akt and ERK phosphorylation in these cells. Infusion of MSC-CM immediately before liver irradiation provided a significant anti-apoptotic effect on SECs and improved the histopathological features of injury in the irradiated liver. MSC-CM also reduced the secretion and expression of inflammatory cytokines and increased the expression of anti-inflammatory cytokines. MSC-derived bioactive components could be a novel therapeutic approach for treating radiation-induced liver injury. (author)

  14. More Robust Test Stand Operations through Next-Gen Real-Time Analysis of Operations Anomalies

    Data.gov (United States)

    National Aeronautics and Space Administration — The Functional Monitoring & Diagnosis (FMD) software (developed by MSC) is a next-generation monitoring & diagnostic software that works by evaluating...

  15. Maintenance of differentiation potential of human bone marrow mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene despite of extensive proliferation

    International Nuclear Information System (INIS)

    Abdallah, Basem M.; Haack-Sorensen, Mandana; Burns, Jorge S.; Elsnab, Birgitte; Jakob, Franz; Hokland, Peter; Kassem, Moustapha

    2005-01-01

    Human bone marrow mesenchymal stem cells (hMSC) represent a population of stem cells that are capable of differentiation into multiple lineages. However, these cells exhibit senescence-associated growth arrest and phenotypic changes during long-term in vitro culture. We have recently demonstrated that overexpression of human telomerase reverse transcriptase (hTERT) in hMSC reconstitutes telomerase activity and extends life span of the cells [Nat. Biotechnol. 20 (2002) 592]. In the present study, we have performed extensive characterization of three independent cell lines derived from the parental hMSC-TERT cell line based on different plating densities during expansion in culture: 1:2 (hMSC-TERT2), 1:4 (hMSC-TERT4), and 1:20 (hMSC-TERT20). The 3 cell lines exhibited differences in morphology and growth rates but they all maintained the characteristics of self-renewing stem cells and the ability to differentiate into multiple mesoderm-type cell lineages: osteoblasts, adipocytes, chondrocytes, and endothelial-like cells over a 3-year period in culture. Also, surface marker studies using flow cytometry showed a pattern similar to that known from normal hMSC. Thus, telomerization of hMSC by hTERT overexpression maintains the stem cell phenotype of hMSC and it may be a useful tool for obtaining enough number of cells with a stable phenotype for mechanistic studies of cell differentiation and for tissue engineering protocols

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

    DEFF Research Database (Denmark)

    Schmal, H; Niemeyer, P; Roesslein, M

    2007-01-01

    . Corresponding with this, C5a induced the migration of PBMC but not of MSC. Dose-dependent and -specific adhesion to fibronectin, fibrinogen, collagen type I and collagen type II could be demonstrated for MSC; in contrast, PBMC did not adhere to any of the investigated proteins. Real-time PCR of receptor...... expression revealed a 12.2-fold higher expression of alphav in MSC compared with PBMC. Incubation of MSC with tumor necrosis factor-alpha (TNFalpha) induced NFkappaB activation and increased the chemotactic response to serum and adhesion to fibronedtin. DISCUSSION: Chemotaxis and adhesion are crucial...

  17. Transplantation of mesenchymal stem cells overexpressing IL10 attenuates cardiac impairments in rats with myocardial infarction.

    Science.gov (United States)

    Meng, Xin; Li, Jianping; Yu, Ming; Yang, Jian; Zheng, Minjuan; Zhang, Jinzhou; Sun, Chao; Liang, Hongliang; Liu, Liwen

    2018-01-01

    Mesenchymal stem cell (MSC) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). In addition, interleukin-10 (IL10) could attenuate MI through suppressing inflammation. Thus, the combination of MSC implantation with IL10 delivery may extend health benefits to ameliorate cardiac injury after MI. Here we established overexpression of IL10 in bone marrow-derived MSC through adenoviral transduction. Cell viability, apoptosis, and IL10 secretion under ischemic challenge in vitro were examined. In addition, MSC was transplanted into the injured hearts in a rat model of MI. Four weeks after the MI induction, MI, cardiac functions, apoptotic cells, and inflammation cytokines were assessed. In response to in vitro oxygen-glucose deprivation (OGD), IL10 overexpression in MSC (Ad.IL10-MSC) enhanced cell viability, decreased apoptosis, and increased IL10 secretion. Consistently, the implantation of Ad.IL10-MSCs into MI animals resulted in more reductions in myocardial infarct size, cardiac impairment, and cell apoptosis, compared to the individual treatments of either MSC or IL10 administration. Moreover, the attenuation of both systemic and local inflammations was most prominent for Ad.IL10-MSC treatment. IL10 overexpression and MSC may exert a synergistic anti-inflammatory effect to alleviate cardiac injury after MI. © 2017 Wiley Periodicals, Inc.

  18. Kardiovaskulaer regeneration med mesenkymale stamceller

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Sørensen, Mandana Haack; Jørgensen, Erik

    2010-01-01

    a multipotent differentiation capacity. Clinical MSC studies on patients with ischaemic heart disease have shown improved left ventricular function and perfusion and also a reduction in infarct size and symptoms. In this short review we provide a status on MSC regenerative treatment in cardiovascular disease.......Treatment with stem cells with a regenerative potential is a new form of therapy that is being studied intensively. Mesenchymal stem cells or stromal cells (MSC) are a promising source of stem cells for regenerative therapy. MSC are easy to isolate and culture, expand in vitro and have...

  19. [Mesenchymal stromal cells in the treatment of graft-versus-host disease: where do we stand?].

    Science.gov (United States)

    Schüle, Silke; Berger, André

    2015-11-01

    Medicinal products based on mesenchymal stromal cells (MSC) are expected to have a therapeutic benefit in a variety of conditions and, accordingly, are being tested in many clinical studies. The treatment and prevention of graft-versus-host disease (GVHD) is one of the world's most widely studied MSC therapy concepts. So far, one MSC medicinal product has been approved for the treatment of GvHD. This article gives an overview of the particular features related to the production of MSC-based medicinal products, the state of non-clinical research, and the clinical development status of MSCs and the associated challenges, especially in the context of GvHD.

  20. Enhanced neuro-therapeutic potential of Wharton's Jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture.

    Science.gov (United States)

    Drela, Katarzyna; Lech, Wioletta; Figiel-Dabrowska, Anna; Zychowicz, Marzena; Mikula, Michał; Sarnowska, Anna; Domanska-Janik, Krystyna

    2016-04-01

    Substantial inconsistencies in mesenchymal stem (stromal) cell (MSC) therapy reported in early translational and clinical studies may indicate need for selection of the proper cell population for any particular therapeutic purpose. In the present study we have examined stromal stem cells derived either from umbilical cord Wharton's Jelly (WJ-MSC) or bone marrow (BM-MSC) of adult, healthy donors. The cells characterized in accordance with the International Society for Cellular Therapy (ISCT) indications as well as other phenotypic and functional parameters have been compared under strictly controlled culture conditions. WJ-MSC, in comparison with BM-MSC, exhibited a higher proliferation rate, a greater expansion capability being additionally stimulated under low-oxygen atmosphere, enhanced neurotrophic factors gene expression and spontaneous tendency toward a neural lineage differentiation commitment confirmed by protein and gene marker induction. Our data suggest that WJ-MSC may represent an example of immature-type "pre-MSC," where a substantial cellular component is embryonic-like, pluripotent derivatives with the default neural-like differentiation. These cells may contribute in different extents to nearly all classical MSC populations adversely correlated with the age of cell donors. Our data suggest that neuro-epithelial markers, like nestin, stage specific embryonic antigens-4 or α-smooth muscle actin expressions, may serve as useful indicators of MSC culture neuro-regeneration-associated potency. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  1. Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis.

    Science.gov (United States)

    Maria, Alexandre T J; Toupet, Karine; Maumus, Marie; Fonteneau, Guillaume; Le Quellec, Alain; Jorgensen, Christian; Guilpain, Philippe; Noël, Danièle

    2016-06-01

    Displaying immunosuppressive and trophic properties, mesenchymal stem/stromal cells (MSC) are being evaluated as promising therapeutic options in a variety of autoimmune and degenerative diseases. Although benefits may be expected in systemic sclerosis (SSc), a rare autoimmune disease with fibrosis-related mortality, MSC have yet to be evaluated in this specific condition. While autologous approaches could be inappropriate because of functional alterations in MSC from patients, the objective of the present study was to evaluate allogeneic and xenogeneic MSC in the HOCl-induced model of diffuse SSc. We also questioned the source of human MSC and compared bone marrow- (hBM-MSC) and adipose-derived MSC (hASC). HOCl-challenged BALB/c mice received intravenous injection of BM-MSC from syngeneic BALB/c or allogeneic C57BL/6 mice, and xenogeneic hBM-MSC or hASC (3 donors each). Skin thickness was measured during the experiment. At euthanasia, histology, immunostaining, collagen determination and RT-qPCR were performed in skin and lungs. Xenogeneic hBM-MSC were as effective as allogeneic or syngeneic BM-MSC in decreasing skin thickness, expression of Col1, Col3, α-Sma transcripts, and collagen content in skin and lungs. This anti-fibrotic effect was not associated with MSC migration to injured skin or with long-term MSC survival. Interestingly, compared with hBM-MSC, hASC were significantly more efficient in reducing skin fibrosis, which was related to a stronger reduction of TNFα, IL1β, and enhanced ratio of Mmp1/Timp1 in skin and lung tissues. Using primary cells isolated from 3 murine and 6 human individuals, this preclinical study demonstrated similar therapeutic effects using allogeneic or xenogeneic BM-MSC while ASC exerted potent anti-inflammatory and remodeling properties. This sets the proof-of-concept prompting to evaluate the therapeutic efficacy of allogeneic ASC in SSc patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Salamon, Achim; Jonitz-Heincke, Anika; Adam, Stefanie; Rychly, Joachim; Müller-Hilke, Brigitte; Bader, Rainer; Lochner, Katrin; Peters, Kirsten

    2013-01-01

    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

  3. Detrimental effects of rat mesenchymal stromal cell pre-treatment in a model of acute kidney rejection

    Directory of Open Access Journals (Sweden)

    Martina eSeifert

    2012-07-01

    Full Text Available Mesenchymal stromal cells (MSC have shown immunomodulatory and tissue repair potential including partial tolerance induction by pre-treatment of donor-specific cells in a rat heart transplantation model. Very recently, we could show that autologous MSC attenuated ischemia reperfusion injury in a highly mismatched donor-recipient rat kidney transplant model. Therefore, we investigated donor-specific MSC pre-treatment in this rat kidney transplantation model to study whether graft function could be improved, or if tolerance could be induced.Donor- and recipient-type MSC or PBS as a control were injected i.v. four days before kidney transplantation. Mycophenolate mofetil (MMF immunosuppression (20 mg/kg body weight was applied for 7 days. Kidney grafts and spleens were harvested between days 8-10 and analyzed by quantitative RT-PCR and immunohistology. In addition, creatinine levels in the blood were measured and serum was screened for the presence of donor-specific antibodies.Surprisingly, application of both donor- and recipient-specific MSC resulted in enhanced humoral immune responses verified by intragraft B cell infiltration and complement factor C4d deposits. Moreover, signs of inflammation and rejection were generally enhanced in both MSC-treated groups relative to PBS control group. Additionally, pre-treatment with donor-specific MSC significantly enhanced the level of donor-specific antibody formation when compared with PBS- or recipient-MSC-treated groups. Pre-treatment with both MSC types resulted in a higher degree of kidney cortex tissue damage and elevated creatinine levels at the time point of rejection. Thus, MSC pre-sensitization in this model impairs the allograft outcome.Our data from this pre-clinical kidney transplantation model indicate that pre-operative MSC administration may not be optimal in kidney transplantation and caution must be exerted before moving forward with clinical studies in order to avoid adverse effects.

  4. Lipopolysaccharide induces proliferation and osteogenic differentiation of adipose-derived mesenchymal stromal cells in vitro via TLR4 activation

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-01-01

    Multipotent mesenchymal stromal cells (MSC) are capable of multi-lineage differentiation and support regenerative processes. In bacterial infections, resident MSC can come intocontact with and need to react to bacterial components. Lipopolysaccharide (LPS), a typical structure of Gram-negative bacteria, increases the proliferation and osteogenic differentiation of MSC. LPS is usually recognized by the toll-like receptor (TLR) 4 and induces pro-inflammatory reactions in numerous cell types. In this study, we quantified the protein expression of TLR4 and CD14 on adipose-derived MSC (adMSC) in osteogenic differentiation and investigated the effect of TLR4 activation by LPS on NF-κB activation, proliferation and osteogenic differentiation of adMSC. We found that TLR4 is expressed on adMSC whereas CD14 is not, and that osteogenic differentiation induced an increase of the amount of TLR4 protein whereas LPS stimulation did not. Moreover, we could show that NF-κB activation via TLR4 occurs upon LPS treatment. Furthermore, we were able to show that competitive inhibition of TLR4 completely abolished the stimulatory effect of LPS on the proliferation and osteogenic differentiation of adMSC. In addition, the inhibition of TLR4 leads to the complete absence of osteogenic differentiation of adMSC, even when osteogenically stimulated. Thus, we conclude that LPS induces proliferation and osteogenic differentiation of adMSC in vitro through the activation of TLR4 and that the TLR4 receptor seems to play a role during osteogenic differentiation of adMSC.

  5. Canine Platelet Lysate Is Inferior to Fetal Bovine Serum for the Isolation and Propagation of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells

    Science.gov (United States)

    Russell, Keith A.; Gibson, Thomas W. G.; Chong, Andrew; Co, Carmon; Koch, Thomas G.

    2015-01-01

    Background Mesenchymal stromal cells (MSC) are increasingly investigated for their clinical utility in dogs. Fetal bovine serum (FBS) is a common culture supplement used for canine MSC expansion. However, FBS content is variable, its clinical use carries risk of an immune response, and its cost is increasing due to global demand. Platelet lysate (PL) has proven to be a suitable alternative to FBS for expansion of human MSC. Hypothesis and Objectives We hypothesized that canine adipose tissue (AT) and bone marrow (BM) MSC could be isolated and expanded equally in PL and FBS at conventionally-used concentrations with differentiation of these MSC unaffected by choice of supplement. Our objectives were to evaluate the use of canine PL in comparison with FBS at four stages: 1) isolation, 2) proliferation, 3) spontaneous differentiation, and 4) directed differentiation. Results 1) Medium with 10% PL was unable to isolate MSC. 2) MSC, initially isolated in FBS-supplemented media, followed a dose-dependent response with no significant difference between PL and FBS cultures at up to 20% (AT) or 30% (BM) enrichment. Beyond these respective peaks, proliferation fell in PL cultures only, while a continued dose-dependent proliferation response was noted in FBS cultures. 3) Further investigation indicated PL expansion culture was inducing spontaneous adipogenesis in concentrations as low as 10% and as early as 4 days in culture. 4) MSC isolated in FBS, but expanded in either FBS or PL, maintained ability to undergo directed adipogenesis and osteogenesis, but not chondrogenesis. Conclusions/Significance Canine PL did not support establishment of MSC colonies from AT and BM, nor expansion of MSC, which appear to undergo spontaneous adipogenesis in response to PL exposure. In vivo studies are warranted to determine if concurrent use of MSC with any platelet-derived products such as platelet-rich plasma are associated with synergistic, neutral or antagonistic effects. PMID:26353112

  6. Canine Platelet Lysate Is Inferior to Fetal Bovine Serum for the Isolation and Propagation of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells.

    Directory of Open Access Journals (Sweden)

    Keith A Russell

    Full Text Available Mesenchymal stromal cells (MSC are increasingly investigated for their clinical utility in dogs. Fetal bovine serum (FBS is a common culture supplement used for canine MSC expansion. However, FBS content is variable, its clinical use carries risk of an immune response, and its cost is increasing due to global demand. Platelet lysate (PL has proven to be a suitable alternative to FBS for expansion of human MSC.We hypothesized that canine adipose tissue (AT and bone marrow (BM MSC could be isolated and expanded equally in PL and FBS at conventionally-used concentrations with differentiation of these MSC unaffected by choice of supplement. Our objectives were to evaluate the use of canine PL in comparison with FBS at four stages: 1 isolation, 2 proliferation, 3 spontaneous differentiation, and 4 directed differentiation.1 Medium with 10% PL was unable to isolate MSC. 2 MSC, initially isolated in FBS-supplemented media, followed a dose-dependent response with no significant difference between PL and FBS cultures at up to 20% (AT or 30% (BM enrichment. Beyond these respective peaks, proliferation fell in PL cultures only, while a continued dose-dependent proliferation response was noted in FBS cultures. 3 Further investigation indicated PL expansion culture was inducing spontaneous adipogenesis in concentrations as low as 10% and as early as 4 days in culture. 4 MSC isolated in FBS, but expanded in either FBS or PL, maintained ability to undergo directed adipogenesis and osteogenesis, but not chondrogenesis.Canine PL did not support establishment of MSC colonies from AT and BM, nor expansion of MSC, which appear to undergo spontaneous adipogenesis in response to PL exposure. In vivo studies are warranted to determine if concurrent use of MSC with any platelet-derived products such as platelet-rich plasma are associated with synergistic, neutral or antagonistic effects.

  7. 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.

  8. 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

  9. Potential of iPSC-Derived Mesenchymal Stromal Cells for Treating Periodontal Disease

    Directory of Open Access Journals (Sweden)

    K. Hynes

    2018-01-01

    Full Text Available Mesenchymal stromal cell-like populations have been derived from mouse-induced pluripotent stem cells (miPSC-MSC with the capability for tissue regeneration. In this study, murine iPSC underwent differentiation towards an MSC-like immunophenotype. Stable miPSC-MSC cultures expressed the MSC-associated markers, CD73, CD105, and Sca-1, but lacked expression of the pluripotency marker, SSEA1, and hematopoietic markers, CD34 and CD45. Functionally, miPSC-MSC exhibited the potential for trilineage differentiation into osteoblasts, adipocytes, and chondrocytes and the capacity to suppress the proliferation of mitogen-activated splenocytes. The efficacy of miPSC-MSC was assessed in an acute inflammation model following systemic or local delivery into mice with subcutaneous implants containing heat-inactivated P. gingivalis. Histological analysis revealed less inflammatory cellular infiltrate within the sponges in mice treated with miPSC-MSC cells delivered locally rather than systemically. Assessment of proinflammatory cytokines in mouse spleens found that CXCL1 transcripts and protein were reduced in mice treated with miPSC-MSC. In a periodontitis model, mice subjected to oral inoculation with P. gingivalis revealed less bone tissue destruction and inflammation within the jaws when treated with miPSC-MSC compared to PBS alone. Our results demonstrated that miPSC-MSC derived from iPSC have the capacity to control acute and chronic inflammatory responses associated with the destruction of periodontal tissue. Therefore, miPSC-MSC present a promising novel source of stromal cells which could be used in the treatment of periodontal disease and other inflammatory systemic diseases such as rheumatoid arthritis.

  10. 78 FR 68444 - Notice of Agreements Filed

    Science.gov (United States)

    2013-11-14

    ...; Oceania Cruises; Paul Gauguin Cruises; Pearl Seas Cruises; Princess Cruises; Regent Seven Seas Cruises.... Agreement No.: 012232. Title: MSC/CMA CGM North West European Continent-US East Coast Service Space Charter... authorizes MSC to charter space to CMA CGM in the trade between the North West European Continent and the U.S...

  11. Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Heile, Anna M B; Wallrapp, Christine; Klinge, Petra M

    2009-01-01

    -protective substance glucagon-like peptide-1 (GLP-1). METHODS: Thirty two Sprague-Dawley rats were randomized to five groups: controls (no CCI), CCI-only, CCI+eMSC, CCI+GLP-1 eMSC, and CCI+empty capsules. On day 14, cisternal cerebro-spinal fluid (CSF) was sampled for measurement of GLP-1 concentration. Brains were...

  12. A novel switched inductor configuration for modified SEPIC DC-to-DC converter for renewable energy application

    DEFF Research Database (Denmark)

    Maroti, Pandav Kiran; Padmanaban, Sanjeevikumar; Blaabjerg, Frede

    2017-01-01

    The proposed work is on the Modified SEPIC Converter (MSC) and its different configuration with switched inductor structure (SI). In this paper, five different configuration of modified SEPIC Converter namely-Modified SEPIC converter without switched inductor configuration (MSC-LLL), Modified SEP...

  13. Destination: Saving Lives and Providing Hope in Haiti

    Science.gov (United States)

    2010-01-01

    the other group, which was led by Andy Busk , field support divi- sion deputy director and ex-MSC chief engineer, and Jim Williams, MSC electri- cal...efforts.” Comfort was able to drop off some of the members of the tiger team on a ferry as it passed by Norfolk. Watts, Busk , and Williams remained

  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. Biomimetic chimeric peptide-tethered hydrogels for human mesenchymal stem cell delivery.

    Science.gov (United States)

    Shim, Gayong; Kim, Gunwoo; Choi, Junhyeok; Yi, TacGhee; Cho, Yun Kyoung; Song, Sun Uk; Byun, Youngro; Oh, Yu-Kyoung

    2015-12-01

    Here, we report a chimeric peptide-tethered fibrin hydrogel scaffold for delivery of human mesenchymal stem cells (hMSC). Osteopontin-derived peptide (OP) was used as an hMSC-tethering moiety. OP showed hMSC adhesion properties and enhanced hMSC proliferation. A natural fibrin-binding protein-derived peptide (FBP) was tested for its ability to tether hMSC to the fibrin gel matrix. FBP loading on fibrin gels was 8.2-fold higher than that of a scrambled peptide (scFBP). FBP-loaded fibrin gels were retained at injection sites longer than scFBP-loaded fibrin gels, showing a 15.9-fold higher photon intensity of fluorescent FBP-grafted fibrin gels than fluorescent scFBP-loaded fibrin gels 48 h after injection. On the basis of the fibrin gel-binding properties of FBP and the hMSC-binding and proliferation-supporting properties of OP, we constructed chimeric peptides containing FBP and OP linked with a spacer (FBPsOP). Four days after transplantation, the survival of hMSC in FBPsOP-grafted fibrin gels was 3.9-fold higher than hMSC in fibrin gels alone. Our results suggest the potential of FBPsOP-grafted fibrin gels as a bioactive delivery system for enhanced survival of stem cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. "But I'm Not Good at Math": The Changing Salience of Mathematical Self-Concept in Shaping Women's and Men's STEM Aspirations

    Science.gov (United States)

    Sax, Linda J.; Kanny, M. Allison; Riggers-Piehl, Tiffani A.; Whang, Hannah; Paulson, Laura N.

    2015-01-01

    Math self-concept (MSC) is considered an important predictor of the pursuit of science, technology, engineering and math (STEM) fields. Women's underrepresentation in the STEM fields is often attributed to their consistently lower ratings on MSC relative to men. Research in this area typically considers STEM in the aggregate and does not account…

  18. The life and fate of mesenchymal stem cells

    NARCIS (Netherlands)

    E. Eggenhofer (Elke); F. Luk (Franka); M.H. Dahlke (Marc); M.J. Hoogduijn (Martin)

    2014-01-01

    textabstractMesenchymal stem cells (MSC) are present throughout the body and are thought to play a role in tissue regeneration and control of inflammation. MSC can be easily expanded in vitro and their potential as a therapeutic option for degenerative and inflammatory disease is therefore

  19. Verification of Checking of the Validity and Effectiveness of Damage

    Directory of Open Access Journals (Sweden)

    Dorin LOZICI-BRINZEI

    2017-06-01

    Full Text Available This paper presents a methodology for identifying some stress concentrators based on the modal analysis performed using MSC Patran and MSC Nastran programs. The influence of a beam crack on its own frequency is practically insignificant. In order to emphasize this concentrator and its position, a modal shape processing method is used, by way of a program developed in EXCEL.

  20. A Software Tool for the Rapid Analysis of the Sintering Behavior of Particulate Bodies

    Science.gov (United States)

    2017-11-01

    for a given thermal history (Pouchly and Maca 2010). Since Su and Johnson’s MSC paper, further development of the MSC theory has occurred (Kiani et...2006;37(11):3337. Pouchly V, Maca K. Master sintering curve: a practical approach to its construction. Science of Sintering. 2010;42(1):25–32. Su H

  1. 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

  2. (Penicillium) marneffei infection in a returning HIV-infected traveller

    African Journals Online (AJOL)

    N P Govender,1,2 MB BCh, MMed, MSc; R E Magobo,1 MSc; T G Zulu,1 Nat Dip Tech; M du Plooy,3 Nat Dip Tech;. C Corcoran,3 MB ChB, MMed. 1 National Institute for Communicable Diseases (Centre for Opportunistic, Tropical and Hospital Infections), National Health. Laboratory Service, Johannesburg, South Africa.

  3. Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α

    Science.gov (United States)

    Liu, Chang; Tang, Xiaojun; Feng, Ruihai; Yao, Genhong; Chen, Weiwei; Li, Wenchao; Liang, Jun; Feng, Xuebing

    2018-01-01

    Objective To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSC) transplantation on joint damage and osteoporosis in collagen-induced arthritis (CIA) mice and to explore the mechanisms by which UC-MSCs modulate the osteogenic differentiation. Methods CIA mice were divided into the following treated groups: UC-MSC transplantation group, antitumor necrosis factor- (TNF-) α group, and zoledronic acid (ZA) group. Microcomputed tomography (micro-CT) was used to analyze the bone morphology parameters. Osteogenic differentiation of treated CIA mice was determined. Bone marrow mesenchymal stem cells (BM-MSCs) from CIA mice were treated with TNF-α in vitro to explore their effects on osteogenesis. Results The arthritis score was significantly reduced in the UC-MSC transplantation and anti-TNF-α-treated CIA groups, compared with control mice (P UC-MSC-treated CIA mice. Impaired osteogenic differentiation functions were indicated by decreased ALP activity (P UC-MSC treatment significantly upregulated the impaired osteogenic differentiation ability in CIA mice. Meanwhile, the serum TNF-α level was decreased significantly in the UC-MSC group. The osteogenesis was reduced with the addition of TNF-α in vitro. Conclusion This study demonstrated that UC-MSC transplantation not only significantly improved the joint damage but also played a beneficial role in osteoporosis in CIA mice. Mechanistically, the improved osteogenic differentiation of CIA under UC-MSC treatment may be achieved by inhibition of TNF-α. PMID:29853911

  4. β1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions

    NARCIS (Netherlands)

    D. Zwolanek (Daniela); M. Flicker (Magdalena); E. Kirstätter (Elisabeth); F. Zaucke (Frank); G.J.V.M. van Osch (Gerjo); R.G. Erben (Reinhold)

    2015-01-01

    textabstractMesenchymal stem cells (MSC) may have great potential for cell-based therapies of osteoarthritis. However, after injection in the joint, only few cells adhere to defective articular cartilage and contribute to cartilage regeneration. Little is known about the molecular mechanisms of MSC

  5. 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.

    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

  6. 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 hypoxi...

  7. EAMJ Modifiable 10.indd

    African Journals Online (AJOL)

    2010-02-02

    Feb 2, 2010 ... MODIFIABLE FACTORS ASSOCIATED WITH ACTIVE PULMONARY TUBERCULOSIS IN A KENYAN PRISON. A. S. Amwayi, MBChB, MSc., ... University of Agriculture and Technology, P.O. Box 62000- 0200, Nairobi, Kenya and E. M. Muchiri, MSc, PhD., Division ..... Diabetes and low BMI. 223452.81.

  8. AGROFORESTERÍA

    OpenAIRE

    Luis Fernando Osorio, Director 6 Simp. For.

    2014-01-01

    Comité científico del simposio Director Luis Fernando Osorio Vélez, Ph.D. Universidad Nacional de Colombia, sede Medellín. Colombia. Agroforestería y silvopastoreo Luis Gonzalo Moscoso H, M.Sc. Forestpa. Colombia. León Escobar Múnera, M.Sc. Forestpa. Colombia.

  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

    2015-08-03

    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. Some aspects of pollution of coastal marine environment of Bombay

    Digital Repository Service at National Institute of Oceanography (India)

    Rokade, M.A.

    stream_size 159 stream_content_type text/plain stream_name Rokade_MSc_thesis.pdf.txt stream_source_info Rokade_MSc_thesis.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 ...

  11. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells has a neutral effect on obesity-induced diabetic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Sebastián D Calligaris

    2013-01-01

    Full Text Available Obesity is a major global health issue. Obese patients develop metabolic syndrome, which is a cluster of clinical features characterized by insulin resistance and dyslipidemia. Its cardiac manifestation, diabetic cardiomyopathy, leads to heart failure. Bone marrow-derived multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSC are envisioned as a therapeutic tool not only for cardiovascular diseases but also for other degenerative conditions. Our aim was to evaluate whether the intravenous administration of MSC modifies cardiac dysfunction in obese mice. To this end, C57BL/6 mice were fed a regular (normal or high-fat diet (obese. Obese animals received the vehicle (obese, a single dose (obese + 1x MSC or three doses (obese + 3x MSC of 0.5x10(6 syngeneic MSC. Two to three months following MSC administration, cardiac function was assessed by cardiac catheterization, at basal condition and after a pharmacological stress. Compared to normal mice, obese mice presented hyperglycemia, hyperinsulinemia, hypercholesterolemia and cardiac dysfunction after stress condition. Exogenous MSC neither improved nor impaired this cardiac dysfunction. Thus, intravenous administration of MSC has neutral effect on obesity-induced diabetic cardiomyopathy

  12. NCBI nr-aa BLAST: CBRC-AGAM-07-0048 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-AGAM-07-0048 ref|YP_069528.1| MscS family mechanosensitive channel [Yersinia pseudotuberculosis... IP 32953] emb|CAH20227.1| MscS family mechanosensitive channel [Yersinia pseudotuberculosis IP 32953] YP_069528.1 1e-106 53% ...

  13. Soil application of formulated Metarhizium brunneum F52 (Hypocreales: Clavicipitaceae) containing microsclerotia controls eggs of Aedes aegypti (Diptera: Culicidae)

    Science.gov (United States)

    We evaluated the potential of a granular formulation of Metarhizium brunneum F52 containing microsclerotia (MbMSc granules) for control of Aedes aegypti (L.) by targeting eggs. MbMSc granules produced infective conidia within 14 days after application to moist potting soil, producing 5.9 × 10**5, 2....

  14. Isolation, culture and intraportal transplantation of rat marrow stromal cell

    International Nuclear Information System (INIS)

    Wang Ping; Wang Jianhua; Yan Zhiping; Li Wentao; Lin Genlai; Hu Meiyu; Wang Yanhong

    2004-01-01

    Objective: To observe the tracing and evolution of marrow stromal cell (MSC) after intraportal transplantation into the liver of homogenous rats, and to provide experimental data for MSC differentiation to hepatocyte in vivo. Methods: The MSC was isolated from the leg bone marrow of adult SD rats, and purified by culture-expanded in vitro. Before transplantation, MSC was labeled with DAPI. Then 10 5 MSC were intraportally transplanted into the homogenous rat liver. Rats were killed at 2 hours and 1, 2, 3 and 4 weeks after transplantation. The cryosection samples of liver and lung were observed under fluorescence microscopy. Results: MSC in vitro culture had high ability of proliferation. Except 4 rats were dead because of abdominal bleeding or infection, other recipients were healthy until sacrificed. The implantation cells were detected by identifying the DAPI labeled MSC in the host livers, but not in the host lungs. Conclusion: Intraportal transplanted MSC could immigrate and survive in the host livers at least for 4 weeks. They could immigrate from the small branches of portal veins to hepatic parenchyma

  15. Effects of high glucose on mesenchymal stem cell proliferation and differentiation

    DEFF Research Database (Denmark)

    Li, Yu-Ming; Schilling, Tatjana; Benisch, Peggy

    2007-01-01

    High glucose (HG) concentrations impair cellular functions and induce apoptosis. Exposition of mesenchymal stem cells (MSC) to HG was reported to reduce colony forming activity and induce premature senescence. We characterized the effects of HG on human MSC in vitro using telomerase-immortalized...

  16. Climate stability in central Anatolia during the Messinian Salinity Crisis

    NARCIS (Netherlands)

    Meijers, Maud J.M.; Peynircioğlu, A. Ahmet; Cosca, Michael A.; Brocard, Gilles Y.; Whitney, Donna L.; Langereis, Cor G.; Mulch, Andreas

    2018-01-01

    Deposition of large amounts of evaporites and erosion of deep canyons within the Mediterranean Basin as a result of reduced basin connectivity with the Atlantic Ocean and the epicontinental Paratethys Sea characterized the Messinian Salinity Crisis (MSC, 5.97–5.33 Ma). The influence of the MSC on

  17. 76 FR 19176 - Shipping Coordinating Committee; Notice of Committee Meeting

    Science.gov (United States)

    2011-04-06

    ...) Maritime Safety Committee (MSC 89) to be held May 11-20, 2011. The primary matters to be considered at MSC... --Technical assistance sub-programme in maritime safety and security --Capacity-building for the... business --Report of the Maritime Safety Committee Members of the public may attend these two meetings up...

  18. Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss

    DEFF Research Database (Denmark)

    Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

    2009-01-01

    Marrow stromal cells (MSC) are thought to be stem cells with osteogenic potential and therefore responsible for the repair and maintenance of the skeleton. Age related bone loss is one of the most prevalent diseases in the elder population. It is controversial whether MSC undergo a process of agi...

  19. 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...

  20. Osteoblastic cells: differentiation and trans-differentiation

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem; Saeed, Hamid

    2008-01-01

    The osteoblast is the bone forming cell and is derived from mesenchymal stem cells (MSC) present among the bone marrow stroma. MSC are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts and adipocytes. Understanding the mechanisms underlying osteoblast different...

  1. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells

    DEFF Research Database (Denmark)

    Dokkedahl, Karin Stenderup; Justesen, Jeannette; Clausen, Christian

    2003-01-01

    Age-related decrease in bone formation is well described. However, the cellular causes are not known. Thus, we have established cultures of bone marrow stromal cells (MSC) from young (aged 18-29 years, n = 6) and old (aged 68-81 years, n = 5) donors. MSC were serially passaged until reaching maxi...

  2. A biological study establishing the endotoxin limit for in vitro proliferation of human mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Yusuke Nomura

    2017-12-01

    Conclusions: Since endotoxins can affect various cellular functions, an endotoxin limit should be set for in vitro MSC cultures. The lowest observed adverse effect level was determined to be 0.1 ng/ml based on the effect on MSC proliferation.

  3. Evaluation of gene delivery strategies to efficiently overexpress functional HLA-G on human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Joana S Boura

    2014-01-01

    Full Text Available Mesenchymal stromal cells (MSC constitutively express low levels of human leukocyte antigen-G (HLA-G, which has been shown to contribute to their immunomodulatory and anti-inflammatory properties. Here, we hypothesized that overexpression of HLA-G on bone marrow-derived MSC would improve their immunomodulatory function, thus increasing their therapeutic potential. Therefore, we investigated which gene transfer system is best suited for delivering this molecule while maintaining its immunomodulatory effects. We performed a side-by-side comparison between three nonviral plasmid-based platforms (pmax-HLA-G1; MC-HLA-G1; pEP-HLA-G1 and a viral system (Lv-HLA-G1 using gene transfer parameters that yielded similar levels of HLA-G1-expressing MSC. Natural killer (NK cell–mediated lysis assays and T cell proliferation assays showed that MSC modified with the HLA-G1 expressing viral vector had significantly lower susceptibility to NK-lysis and significantly reduced T cell proliferation when compared to nonmodified cells or MSC modified with plasmid. We also show that, in plasmid-modified MSC, an increase in Toll-like receptor (TLR9 expression is the mechanism responsible for the abrogation of HLA-G1's immunomodulatory effect. Although MSC can be efficiently modified to overexpress HLA-G1 using viral and nonviral strategies, only viral-based delivery of HLA-G1 is suitable for improvement of MSC's immunomodulatory properties.

  4. Raw mechanically separated chicken meat and salmon protein hydrolysate as protein sources in extruded dog food

    DEFF Research Database (Denmark)

    Tjernsbekk, M. T.; Tauson, A. H.; Kraugerud, O. F.

    2017-01-01

    Protein quality was evaluated for mechanically separated chicken meat (MSC) and salmon protein hydrolysate (SPH), and for extruded dog foods where MSC or SPH partially replaced poultry meal (PM). Apparent total tract digestibility (ATTD) of crude protein (CP) and amino acids (AA) in the protein...

  5. [Construction of fetal mesenchymal stem cell cDNA subtractive library].

    Science.gov (United States)

    Yang, Li; Wang, Dong-Mei; Li, Liang; Bai, Ci-Xian; Cao, Hua; Li, Ting-Yu; Pei, Xue-Tao

    2002-04-01

    To identify differentially expressed genes between fetal mesenchymal stem cell (MSC) and adult MSC, especially specified genes expressed in fetal MSC, a cDNA subtractive library of fetal MSC was constructed using suppression subtractive hybridization (SSH) technique. At first, total RNA was isolated from fetal and adult MSC. Using SMART PCR synthesis method, single-strand and double-strand cDNAs were synthesized. After Rsa I digestion, fetal MSC cDNAs were divided into two groups and ligated to adaptor 1 and adaptor 2 respectively. Results showed that the amplified library contains 890 clones. Analysis of 890 clones with PCR demonstrated that 768 clones were positive. The positive rate is 86.3%. The size of inserted fragments in these positive clones was between 0.2 - 1 kb, with an average of 400 - 600 bp. SSH is a convenient and effective method for screening differentially expressed genes. The constructed cDNA subtractive library of fetal MSC cDNA lays solid foundation for screening and cloning new and specific function related genes of fetal MSC.

  6. Tumorigenic Heterogeneity in Cancer Stem Cells Evolved from Long-term Cultures of Telomerase-Immortalized

    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...

  7. 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

  8. The effect of allogenic versus autologue mesenchymal stem cells in bone reconstructio

    DEFF Research Database (Denmark)

    Jensen, Stefan; Overgaard, Søren; Ding, Ming

    2008-01-01

    with allogenic MSC (group#3) proved to have a significant higher mean SFE (Fisher's LSD-test). The other groups (#1 and #2) had a slightly higher mean SFE (Table 2). Discussion and Conclusion: There are shown two interesting things in this minor pilot-study. There is a trend showing, that the use of MSC has...

  9. Kardiovaskulaer regeneration med mesenkymale stamceller

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Sørensen, Mandana Haack; Jørgensen, Erik

    2010-01-01

    Treatment with stem cells with a regenerative potential is a new form of therapy that is being studied intensively. Mesenchymal stem cells or stromal cells (MSC) are a promising source of stem cells for regenerative therapy. MSC are easy to isolate and culture, expand in vitro and have a multipot...

  10. East African Medical Journal

    African Journals Online (AJOL)

    Paris, France, K. C. Takarinda, BSc, MSc, International Union Against Tuberculosis and Lung ... Kenya and T. Galgalo, MSc, African Field Epidemiology Network. ... times more likely to develop active TB than those ... isoniazid preventive therapy (IPT), intensified TB case ... The capital city, where this study took place, had a.

  11. 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.

  12. 78 FR 69430 - Center for Scientific Review; Notice of Closed Meetings

    Science.gov (United States)

    2013-11-19

    ... Rockledge Drive, Room 3211, MSC 7808, Bethesda, MD 20892, 301-435- 0903, [email protected]csr.nih.gov . This notice is being published less than 15 days prior to the meeting due to the timing limitations imposed by... Health, 6701 Rockledge Drive, Room 3211, MSC 7808, Bethesda, MD 20892,301-435- 0903, [email protected]csr.nih.gov...

  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. 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...

  15. Osteosarcoma models : understanding complex disease

    NARCIS (Netherlands)

    Mohseny, Alexander Behzad

    2012-01-01

    A mesenchymal stem cell (MSC) based osteosarcoma model was established. The model provided evidence for a MSC origin of osteosarcoma. Normal MSCs transformed spontaneously to osteosarcoma-like cells which was always accompanied by genomic instability and loss of the Cdkn2a locus. Accordingly loss of

  16. Development of the multistep compound process calculation code

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Toshihiko [Kyushu Univ., Fukuoka (Japan)

    1998-03-01

    A program `cmc` has been developed to calculate the multistep compound (MSC) process by Feshback-Kerman-Koonin. A radial overlap integral in the transition matrix element is calculated microscopically, and comparisons are made for neutron induced {sup 93}Nb reactions. Strengths of the two-body interaction V{sub 0} are estimated from the total MSC cross sections. (author)

  17. Patient-specific age: the other side of the coin in advanced mesenchymal stem cell therapy

    Directory of Open Access Journals (Sweden)

    Magdalena Maria Schimke

    2015-12-01

    Full Text Available Multipotential mesenchymal stromal cells (MSC are present as a rare subpopulation within any type of stroma in the body of higher animals. Prominently, MSC have been recognized to reside in perivascular locations, supposedly maintaining blood vessel integrity. During tissue damage and injury, MSC/pericytes become activated, evade from their perivascular niche and are thus assumed to support wound healing and tissue regeneration.In vitro MSC exhibit demonstrated capabilities to differentiate into a wide variety of tissue cell types. Hence, many MSC-based therapeutic approaches have been performed to address bone, cartilage or heart regeneration. Furthermore, prominent studies showed efficacy of ex vivo expanded MSC to countervail graft-versus-host-disease. Therefore, additional fields of application are presently conceived, in which MSC-based therapies potentially unfold beneficial effects, such as amelioration of non-healing conditions after tendon or spinal cord injury, as well as neuropathies. Working along these lines, MSC-based scientific research has been forged ahead to prominently occupy the clinical stage.Aging is to a great deal stochastic by nature bringing forth changes in an individual fashion. Yet, is aging of stem cells or/and their corresponding niche considered a determining factor for outcome and success of clinical therapies?

  18. Longitudinal Mechano-Sorptive Creep Behavior of Chinese Fir in Tension during Moisture Adsorption Processes.

    Science.gov (United States)

    Peng, Hui; Lu, Jianxiong; Jiang, Jiali; Cao, Jinzhen

    2017-08-10

    To provide comprehensive data on creep behaviors at relative humidity (RH) isohume conditions and find the basic characteristics of mechano-sorptive (MS) creep (MSC), the tensile creep behaviors, "viscoelastic creep (VEC)" at equilibrium moisture content and MSC during adsorption process, were performed on Chinese fir in the longitudinal direction under 20%, 40%, 60% and 80% RH (25 °C) and at 1, 1.3, and 1.6 MPa, respectively. The free swelling behavior was also measured, where the climate conditions corresponded with MSC tests. Based on the databases of free swelling, VEC, and MSC, the existence of MS effect was examined, and the application of the rheological model under the assumption of partitioned strain was investigated. The results revealed that both VEC and MSC increased with magnitude of applied stress, and the increasing RH level. Under all RH isohume conditions, the total strain of MSC was greater than that of VEC. The influence of RH level on VEC was attributed to the water plasticization effect, whereas that on MSC was presumed to be the effect of water plasticization and unstable state in the wood cell wall. In addition, the RH level promoted the relaxation behavior in MSC, while it slightly affected the relaxation behavior in VEC. In the future, the rheological model could consider the link between load configuration and the anatomic structural feature of wood.

  19. Kardiovaskulaer regeneration med mesenkymale stamceller

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Sørensen, Mandana Haack; Jørgensen, Erik

    2010-01-01

    Treatment with stem cells with a regenerative potential is a new form of therapy that is being studied intensively. Mesenchymal stem cells or stromal cells (MSC) are a promising source of stem cells for regenerative therapy. MSC are easy to isolate and culture, expand in vitro and have...

  20. 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.

  1. Persistence of DNA damage following exposure of human bladder cells to chronic monomethylarsonous acid

    International Nuclear Information System (INIS)

    Wnek, S.M.; Medeiros, M.K.; Eblin, K.E.; Gandolfi, A.J.

    2009-01-01

    Malignant transformation was demonstrated in UROtsa cells following 52-weeks of exposure to 50 nM monomethylarsonous acid (MMA III ); the result was the malignantly transformed cell line, URO-MSC. URO-MSC cells were used to study the induction of DNA damage and the alteration of DNA repair enzymes in both the presence of MMA III [URO-MSC(+)] and after subsequent removal of MMA III [URO-MSC(-)] following chronic, low-level exposure. In the presence of MMA III , URO-MSC(+) cells demonstrated a sustained increase in DNA damage following 12-weeks of exposure; in particular, a significant increase in DNA single-strand breaks at 12-weeks of exposure consistently elevated through 52 weeks. The persistence of DNA damage in URO-MSC cells was assessed after a 2-week removal of MMA III . URO-MSC(-) cells demonstrated a decrease in DNA damage compared to URO-MSC(+); however, DNA damage in URO-MSC(-) remained significantly elevated when compared to untreated UROtsa and increased in a time-dependent manner. Reactive oxygen species (ROS) were demonstrated to be a critical component in the generation of DNA damage determined through the incubation of ROS scavengers with URO-MSC cells. Poly (ADP-ribose) polymerase (PARP) is a key repair enzyme in DNA single-strand break repair. URO-MSC(+) resulted in a slight increase in PARP activity after 36-weeks of MMA III exposure, suggesting the presence of MMA III is inhibiting the increase in PARP activity. In support, PARP activity in URO-MSC(-) increased significantly, coinciding with a subsequent decrease in DNA damage demonstrated in URO-MSC(-) compared to URO-MSC(+). These data demonstrate that chronic, low-level exposure of UROtsa cells to 50 nM MMA III results in: the induction of DNA damage that remains elevated upon removal of MMA III ; increased levels of ROS that play a role in MMA III induced-DNA damage; and decreased PARP activity in the presence of MMA III .

  2. A Novel Corynebacterium glutamicum l-Glutamate Exporter.

    Science.gov (United States)

    Wang, Yu; Cao, Guoqiang; Xu, Deyu; Fan, Liwen; Wu, Xinyang; Ni, Xiaomeng; Zhao, Shuxin; Zheng, Ping; Sun, Jibin; Ma, Yanhe

    2018-03-15

    Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyperproduction of biochemicals using microbial cell factories. The identification and characterization of transporters are therefore of great significance for the understanding and engineering of transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists extensively in Corynebacterium glutamicum strains but is distinct from the only known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate-producing C. glutamicum strain. MscCG2 was predicted to possess three transmembrane helices in the N-terminal region and located in the cytoplasmic membrane, which are typical structural characteristics of the mechanosensitive channel of small conductance. MscCG2 has a low amino acid sequence identity (23%) to MscCG and evolved separately from MscCG with four transmembrane helices. Despite the considerable differences between MscCG2 and MscCG in sequence and structure, gene deletion and complementation confirmed that MscCG2 also functioned as an l-glutamate exporter and an osmotic safety valve in C. glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes were transcribed in similar patterns and not induced by l-glutamate-producing conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion was activated by biotin limitation or penicillin treatment and that constitutive l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2 (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino acid transport and provide additional targets for exporter engineering. IMPORTANCE The exchange of matter, energy, and information with surroundings is fundamental for cellular metabolism. Therefore, studying transport systems that are essential for these processes is of great significance. Besides, transport systems of bacterial cells are usually related to

  3. Homing of mesenchymal stem cells: mechanistic or stochastic? Implications for targeted delivery in arthritis.

    Science.gov (United States)

    Eseonu, Onyedikachi I; De Bari, Cosimo

    2015-02-01

    Mesenchymal stem cells (MSCs) are multipotent cells with the capacity to undergo chondrogenic differentiation. Systemically administered MSCs have been shown to preferentially accumulate at sites of tissue damage and inflammation, thus MSC-based therapy holds great promise for the treatment of inflammatory diseases such as RA. Modulation of MSC homing may allow targeted delivery of systemically administered MSCs to damaged articular cartilage, where they can suppress immune-mediated cartilage destruction and contribute to cartilage repair via a combination of chondrogenic differentiation and paracrine stimulation of intrinsic residual repair. To harness the potential of MSC homing, a thorough understanding of the mechanism is key. This review discusses current knowledge of the mechanism of MSC homing to injured/inflamed tissue and its implications for targeted MSC-based therapy in arthritis. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Enhanced Adipogenicity of Bone Marrow Mesenchymal Stem Cells in Aplastic Anemia

    Directory of Open Access Journals (Sweden)

    Naresh Kumar Tripathy

    2014-01-01

    Full Text Available Fatty bone marrow (BM and defective hematopoiesis are a pathologic hallmark of aplastic anemia (AA. We have investigated adipogenic and osteogenic potential of BM mesenchymal stem cells (BM-MSC in 10 AA patients (08 males and 02 females with median age of 37 years (range: 06 to 79 years and in the same number of age and sex matched controls. It was observed that BM-MSC of AA patients had a morphology, phenotype, and osteogenic differentiation potential similar to control subjects but adipocytes differentiated from AA BM-MSC had a higher density and larger size of lipid droplets and they expressed significantly higher levels of adiponectin and FABP4 genes and proteins as compared to control BM-MSC (P<0.01 for both. Thus our data shows that AA BM-MSC have enhanced adipogenicity, which may have an important implication in the pathogenesis of the disease.

  5. Cell-based Therapy for Acute Organ Injury: Preclinical Evidence and On-going Clinical Trials Using Mesenchymal Stem Cells

    Science.gov (United States)

    Monsel, Antoine; Zhu, Ying-gang; Gennai, Stephane; Hao, Qi; Liu, Jia; Lee, Jae W.

    2014-01-01

    Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver or brain. Genomic, proteomic and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of pro-mitotic, anti-apoptotic, anti-inflammatory and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, we review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use. PMID:25211170

  6. Analysis and Verification of Message Sequence Charts of Distributed Systems with the Help of Coloured Petri Nets

    Directory of Open Access Journals (Sweden)

    S. A. Chernenok

    2014-01-01

    Full Text Available The standard language of message sequence charts MSC is intended to describe scenarios of object interaction. Due to their expressiveness and simplicity MSC diagrams are widely used in practice at all stages of system design and development. In particular, the MSC language is used for describing communication behavior in distributed systems and communication protocols. In this paper the method for analysis and verification of MSC and HMSC diagrams is considered. The method is based on the translation of (HMSC into coloured Petri nets. The translation algorithms cover most standard elements of the MSC including data concepts. Size estimates of the CPN which is the result of the translation are given. Properties of the resulting CPN are analyzed and verified by using the known system CPN Tools and the CPN verifier based on the known tool SPIN. The translation method has been demonstrated by the example.

  7. Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Horwood, Nicole J.; Dazzi, Francesco; Zaher, Walid

    2012-01-01

    Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth...... and differentiation of hematopoietic stem cells (HSC) and hematopoiesis. These cells have been described as important immunoregulators due to their ability to suppress T cells proliferation. MSC can also directly contribute to tissue repair by migrating to sites of injury and providing a source of cells...... for differentiation and/or providing bystander support for resident stromal cells. This chapter discusses the cellular and molecular properties of MSC, the mechanisms by which they can modulate immune responses and the clinical applications of MSC in disorders such as graft-versus-host disease and aplastic anaemia...

  8. 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

    Human mesenchymal stem cells (hMSC) are currently being introduced for cell therapy, yet, antibodies specific for native and differentiated MSCs are required for their identification prior to clinical use. Herein, high quality antibodies against MSC surface proteins were developed by immunizing...... 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...... 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...

  9. Human Serum is as Efficient as Fetal Bovine Serum in Supporting Proliferation and Differentiation of Human Multipotent Stromal (Mesenchymal) Stem Cells In Vitro and In Vivo

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Haack-Sørensen, Mandana; Al-Nbaheen, May

    2011-01-01

    BACKGROUND: Human multipotent stromal (skeletal, mesenchymal) stem cells (hMSC) are employed in an increasing number of clinical trials for tissue regeneration of age-related degenerative diseases. However, routine use of fetal bovine sera (FBS) for their in vitro expansion is not optimal and may......) or adipocytic markers (PPAR-gamma2, lipoprotein lipase (LPL), aP2), respectively. In order to test for the functional capacity of hMSC-TERT that have been maintained in long-term cultures in the presence of HuS vs. FBS, the cells were mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) and implanted...... subcutaneously in immune deficient mice. hMSC maintained in HuS vs. FBS formed comparable heterotopic bone. DISCUSSION: Human serum can support proliferation and differentiation of hMSC in vitro and can maintain their bone forming capacity in vivo. The use of human serum in cell cultures of hMSC intended...

  10. Musculoskeletal complaints among nurses related to patient handling tasks and psychosocial factors - Based on logbook registrations

    DEFF Research Database (Denmark)

    Warming, S.; Precht, D.H.; Suadicani, P.

    2009-01-01

    The aims were to evaluate the inter-method reliability of a registration sheet for patient handling tasks, to study the day-to-day variation of musculoskeletal complaints (MSC) and to examine whether patient handling tasks and psychosocial factors were associated with MSC. Nurses (n = 148...... transfer and care tasks. The numbers of nurses reporting MSC and the level of pain increased significantly during the three working days (15%-30% and 17%-37%, respectively) and decreased on the day off. Stress and transfer task were associated with LPB and transfer tasks were associated with KP. Our...... results confirm a relationship between work factors and MSC and indicate that logs could be one way to obtain a better understanding of the complex interaction of various nursing working conditions in relation to MSC. (C) 2008 Elsevier Ltd. All rights reserved Udgivelsesdato: 2009/7...

  11. 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...... were cell-free beads and beads containing unmodified MSCs (bead-MSC), n = 4-5 per group. Echocardiography confirmed left ventricular (LV) dysfunction at time of delivery in all groups. Four weeks after intervention, only the bead-GLP-1 MSC group demonstrated LV function improvement toward baseline...... 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...

  12. Clinical information system based on the medical smart card.

    Science.gov (United States)

    Danon, Y L; Saiag, E

    2000-07-01

    Over the last 5 years Israel has implemented a nationwide health insurance plan covering the entire population of the country. We have developed a clinical information system based on electronic-chip health care medical smart cards. Health care cards are used in several European countries and chip smart cards have been successful in many sectors. Our project involves the community use of the MSC, thereby enabling health care professionals to skillfully employ card systems in the health care sector. This system can easily arrange electronic medical charts in clinics, facilitating the confidential sharing of personal health databases among health professionals. To develop an MSC applicable for daily use in the community and hospital system. The MSC project, currently underway in Israel and the USA, will aid in determining the costs, benefits and feasibility of the MSC. Successful implementation of the MSC in chosen clinics will promote a nationwide willingness to adopt this promising technology.

  13. 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......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 (h......, was deposited in the scaffold concavities. Here, mature osteoblasts stained positively for differentiated osteoblast markers TAZ, biglycan, osteocalcin, and phospho-AKT. Quantification of collagen birefringence and relatively high expression of genes for matrix proteins, including type I collagen, biglycan...

  14. Human Stromal (Mesenchymal) Stem Cells from Bone Marrow, Adipose Tissue and Skin Exhibit Differences in Molecular Phenotype and Differentiation Potential

    DEFF Research Database (Denmark)

    Al-Nbaheen, May; Vishnubalaji, Radhakrishnan; Ali, Dalia

    2013-01-01

    Human stromal (mesenchymal) stem cells (hMSCs) are multipotent stem cells with ability to differentiate into mesoderm-type cells e.g. osteoblasts and adipocytes and thus they are being introduced into clinical trials for tissue regeneration. Traditionally, hMSCs have been isolated from bone marrow......, but the number of cells obtained is limited. Here, we compared the MSC-like cell populations, obtained from alternative sources for MSC: adipose tissue and skin, with the standard phenotype of human bone marrow MSC (BM-MSCs). MSC from human adipose tissue (human adipose stromal cells (hATSCs)) and human skin......, MSC populations obtained from different tissues exhibit significant differences in their proliferation, differentiation and molecular phenotype, which should be taken into consideration when planning their use in clinical protocols....

  15. Mesenchymal stem cells as a novel vaccine platform

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    Suzanne L. Tomchuck

    2012-11-01

    Full Text Available Vaccines are the most efficient and cost-effective means of preventing infectious disease. However, traditional vaccine approaches have thus far failed to provide protection against human immunodeficiency virus (HIV, tuberculosis, malaria and many other diseases. New approaches to vaccine development are needed to address some of these intractable problems. In this report, we review the literature identifying stimulatory effects of mesenchymal stem cells (MSC on immune responses and explore the potential for MSC as a novel, universal vaccination platform. MSC are unique bone marrow-derived multipotent progenitor cells that are presently being exploited as gene therapy vectors for a variety of conditions, including cancer and autoimmune diseases. Although MSC are predominantly known for anti-inflammatory properties during allogeneic MSC transplant, there is evidence that MSC can actually promote adaptive immunity under certain settings. MSC have also demonstrated some success in anti-cancer therapeutic vaccines and anti-microbial prophylactic vaccines, as we report, for the first time, the ability of modified MSC to express and secrete a viral antigen that stimulates antigen-specific antibody production in vivo. We hypothesize that the unique properties of modified MSC may enable MSC to serve as an unconventional but innovative, vaccine platform. Such a platform would be capable of expressing hundreds of proteins, thereby generating a broad array of epitopes with correct post-translational processing, mimicking natural infection. By stimulating immunity to a combination of epitopes, it may be possible to develop prophylactic and even therapeutic vaccines to tackle major health problems including those of non-microbial and microbial origin, including cancer, or an infectious disease like HIV, where traditional vaccination approaches have failed.

  16. Human Umbilical Cord Mesenchymal Stem Cells: Subpopulations and Their Difference in Cell Biology and Effects on Retinal Degeneration in RCS Rats.

    Science.gov (United States)

    Wang, L; Li, P; Tian, Y; Li, Z; Lian, C; Ou, Q; Jin, C; Gao, F; Xu, J-Y; Wang, J; Wang, F; Zhang, J; Zhang, J; Li, W; Tian, H; Lu, L; Xu, G-T

    2017-01-01

    Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential candidates for treating retinal degeneration (RD). To further study the biology and therapeutic effects of the hUC-MSCs on retinal degeneration. Two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated by single-cell cloning method and their therapeutic functions were compared in RCS rat, a RD model. Although both subsets satisfied the basic requirements for hUC-MSCs, they were significantly different in morphology, proliferation rate, differentiation capacity, phenotype and gene expression. Furthermore, only the smaller, fibroblast-like, faster growing subset hUC-MSC1 displayed stronger colony forming potential as well as adipogenic and osteogenic differentiation capacities. When the two subsets were respectively transplanted into the subretinal spaces of RCS rats, both subsets survived, but only hUC-MSC1 expressed RPE cell markers Bestrophin and RPE65. More importantly, hUC-MSC1 showed stronger rescue effect on the retinal function as indicated by the higher b-wave amplitude on ERG examination, thicker retinal nuclear layer, and decreased apoptotic photoreceptors. When both subsets were treated with interleukin-6, mimicking the inflammatory environment when the cells were transplanted into the eyes with degenerated retina, hUC-MSC1 expressed much higher levels of trophic factors in comparison with hUC-MSC2. The data here, in addition to prove the heterogeneity of hUC-MSCs, confirmed that the stronger therapeutic effects of hUC-MSC1 were attributed to its stronger anti-apoptotic effect, paracrine of trophic factors and potential RPE cell differentiation capacity. Thus, the subset hUC-MSC1, not the other subset or the ungrouped hUC-MSCs should be used for effective treatment of RD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Instant stem cell therapy: Characterization and concentration of human mesenchymal stem cells in vitro

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    P Kasten

    2008-10-01

    Full Text Available In regenerative medicine, there is an approach to avoid expansion of the mesenchymal stem cell (MSC before implantation. The aim of this study was to compare methods for instant MSC therapy by use of a portable, automatic and closed system centrifuge that allows for the concentration of MSCs. The main outcome measures were the amount of MSCs per millilitre of bone marrow (BM, clusters of differentiation (CD, proliferation and differentiation capacities of the MSC. A volume reduction protocol was compared to the traditional laboratory methods of isolation using a Ficoll gradient and native BM. Fifty millilitres of BM were obtained from haematologically healthy male Caucasians (n=10, age 8 to 49 years. The number of colony forming units-fibroblast (CFU-F/ml BM was highest in the centrifuge volume reduction protocol, followed by the native BM (not significant, the centrifuge Ficoll (p=0.042 and the manual Ficoll procedure (p=0.001. The MSC of all groups could differentiate into the mesenchymal lineages without significant differences between the groups. The CD pattern was identical for all groups: CD13+; CD 44+; CD73 +; CD90+; CD105+; HLA-A,B,C+; CD14-; CD34-; CD45-; CD271-; HLA-DR-. In a further clinical pilot study (n=5 with 297 ml BM (SD 18.6, the volume reduction protocol concentrated the MSC by a factor of 14: there were 1.08 x 102 MSC/ml BM (standard deviation (SD 1.02 x 102 before concentration, 14.8 x 102 MSC/ ml BM (SD 12.4 x 102 after concentration, and on average 296 x 102 MSC (SD 248.9 x 102, range 86.4-691.5 x 102 were available for MSC therapy. The volume reduction protocol of the closed centrifuge allows for the highest concentration of the MSC, and therefore, is a promising candidate for instant stem cell therapy.

  18. Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses.

    Science.gov (United States)

    Carrade, Danielle D; Owens, Sean D; Galuppo, Larry D; Vidal, Martin A; Ferraro, Gregory L; Librach, Fred; Buerchler, Sabine; Friedman, Michael S; Walker, Naomi J; Borjesson, Dori L

    2011-04-01

    The development of an allogeneic mesenchymal stem cell (MSC) product to treat equine disorders would be useful; however, there are limited in vivo safety data for horses. We hypothesized that the injection of self (autologous) and non-self (related allogeneic or allogeneic) MSC would not elicit significant alterations in physical examination, gait or synovial fluid parameters when injected into the joints of healthy horses. Sixteen healthy horses were used in this study. Group 1 consisted of foals (n = 6), group 2 consisted of their dams (n = 5) and group 3 consisted of half-siblings (n = 5) to group 1 foals. Prior to injection, MSC were phenotyped. Placentally derived MSC were injected into contralateral joints and MSC diluent was injected into a separate joint (control). An examination, including lameness evaluation and synovial fluid analysis, was performed at 0, 24, 48 and 72 h post-injection. MSC were major histocompatibility complex (MHC) I positive, MHC II negative and CD86 negative. Injection of allogeneic MSC did not elicit a systemic response. Local responses such as joint swelling or lameness were minimal and variable. Intra-articular MSC injection elicited marked inflammation within the synovial fluid (as measured by nucleated cell count, neutrophil number and total protein concentration). However, there were no significant differences between the degree and type of inflammation elicited by self and non-self-MSC. The healthy equine joint responds similarly to a single intra-articular injection of autologous and allogeneic MSC. This pre-clinical safety study is an important first step in the development of equine allogeneic stem cell therapies.

  19. Human platelet lysate in mesenchymal stromal cell expansion according to a GMP grade protocol: a cell factory experience.

    Science.gov (United States)

    Becherucci, Valentina; Piccini, Luisa; Casamassima, Serena; Bisin, Silvia; Gori, Valentina; Gentile, Francesca; Ceccantini, Riccardo; De Rienzo, Elena; Bindi, Barbara; Pavan, Paola; Cunial, Vanessa; Allegro, Elisa; Ermini, Stefano; Brugnolo, Francesca; Astori, Giuseppe; Bambi, Franco

    2018-05-02

    The use of platelet lysate (PL) for the ex-vivo expansion of mesenchymal stromal/stem cells (MSCs) was initially proposed by Doucet et al. in 2005, as an alternative to animal serum. Moreover, regulatory authorities discourage the use of fetal bovine serum (FBS) or other animal derivatives, to avoid risk of zoonoses and xenogeneic immune reactions. Even if many studies investigated PL composition, there still are some open issues related to its use in ex-vivo MSC expansion, especially according to good manufacturing practice (GMP) grade protocols. As an authorized cell factory, we report our experience using standardized PL produced by Azienda Ospedaliero Universitaria Meyer Transfusion Service for MSC expansion according to a GMP grade clinical protocol. As suggested by other authors, we performed an in-vitro test on MSCs versus MSCs cultured with FBS that still represents the best way to test PL batches. We compared 12 MSC batches cultured with DMEM 5% PL with similar batches cultured with DMEM 10% FBS, focusing on the MSC proliferation rate, MSC surface marker expression, MSC immunomodulatory and differentiation potential, and finally MSC relative telomere length. Results confirmed the literature data as PL increases cell proliferation without affecting the MSC immunophenotype, immunomodulatory potential, differentiation potential and relative telomere length. PL can be considered a safe alternative to FBS for ex-vivo expansion of MSC according to a GMP grade protocol. Our experience confirms the literature data: a large number of MSCs for clinical applications can be obtained by expansion with PL, without affecting the MSC main features. Our experience underlines the benefits of a close collaboration between the PL producers (transfusion service) and the end users (cell factory) in a synergy of skills and experiences that can lead to standardized PL production.

  20. 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.

  1. Characterization and Immunomodulatory Effects of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells.

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    Keith A Russell

    Full Text Available Mesenchymal stromal cells (MSC hold promise for both cell replacement and immune modulation strategies owing to their progenitor and non-progenitor functions, respectively. Characterization of MSC from different sources is an important and necessary step before clinical use of these cells is widely adopted. Little is known about the biology and function of canine MSC compared to their mouse or human counterparts. This knowledge-gap impedes development of canine evidence-based MSC technologies.We hypothesized that canine adipose tissue (AT and bone marrow (BM MSC (derived from the same dogs will have similar differentiation and immune modulatory profiles. Our objectives were to evaluate progenitor and non-progenitor functions as well as other characteristics of AT- and BM-MSC including 1 proliferation rate, 2 cell surface marker expression, 3 DNA methylation levels, 4 potential for trilineage differentiation towards osteogenic, adipogenic, and chondrogenic cell fates, and 5 immunomodulatory potency in vitro.1 AT-MSC proliferated at more than double the rate of BM-MSC (population doubling times in days for passage (P 2, AT: 1.69, BM: 3.81; P3, AT: 1.80, BM: 4.06; P4, AT: 2.37, BM: 5.34; P5, AT: 3.20, BM: 7.21. 2 Canine MSC, regardless of source, strongly expressed cell surface markers MHC I, CD29, CD44, and CD90, and were negative for MHC II and CD45. They also showed moderate expression of CD8 and CD73 and mild expression of CD14. Minor differences were found in expression of CD4 and CD34. 3 Global DNA methylation levels were significantly lower in BM-MSC compared to AT-MSC. 4 Little difference was found between AT- and BM-MSC in their potential for adipogenesis and osteogenesis. Chondrogenesis was poor to absent for both sources in spite of adding varying levels of bone-morphogenic protein to our standard transforming growth factor (TGF-β3-based induction medium. 5 Immunomodulatory capacity was equal regardless of cell source when tested in

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

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    Lynn Brandon Williams

    2016-07-01

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

  3. Comparison of human sodium iodide symporter (hNIS) gene expression between lentiviral and adenoviral vectors in rat mesenchymal stem cell

    International Nuclear Information System (INIS)

    Park, So Yeon; Lee, Won Woo; Kim, Sung Jin; Lee, Heui Ran; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun

    2007-01-01

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirus-mediated delivery systems has not been done. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated stably hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning the hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and Rad-hNIS transduced rMSC (adeno-hNIS-rMSC) was evaluated for the hNIS expression 48 hours post infection at MOI 1, 5, 20, 50, and 100. The hNIS expression in lenti-hNIS-rMSC or adeno-hNIS-rMSC was assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry using mono-clonal anti-hNIS antibody revealed that intensity of hNIS immunoreactivity in lenti-hNIS-rMSC was greater than that in adeno-hNIS-rMSC at MOl 20 but lower than that at MOl 50. Western blot analysis also showed that lenti-hNIS-rMSC was intermediate between adeno-hNIS-rMSCs at MOl 20 and 50 in hNIS expression. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (297046659 picomole/106 cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (61682134 picomole/106 cells). These results suggest that lentivirus mediated hNIS expression is greater in terms of hNIS function but lower in terms of hNIS protein amount than adenovirus mediated hNIS expression 48 hours post infection. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative viral efficiency of transgene expression

  4. Biodistribution and Immunogenicity of Allogeneic Mesenchymal Stem Cells in a Rat Model of Intraarticular Chondrocyte Xenotransplantation

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    Maribel Marquina

    2017-11-01

    Full Text Available Xenogeneic chondrocytes and allogeneic mesenchymal stem cells (MSC are considered a potential source of cells for articular cartilage repair. We here assessed the immune response triggered by xenogeneic chondrocytes when injected intraarticularly, as well as the immunoregulatory effect of allogeneic bone marrow-derived MSC after systemic administration. To this end, a discordant xenotransplantation model was established by injecting three million porcine articular chondrocytes (PAC into the femorotibial joint of Lewis rats and monitoring the immune response. First, the fate of MSC injected using various routes was monitored in an in vivo imaging system. The biodistribution revealed a dependency on the injection route with MSC injected intravenously (i.v. succumbing early after 24 h and MSC injected intraperitoneally (i.p. lasting locally for at least 5 days. Importantly, no migration of MSC to the joint was detected in rats previously injected with PAC. MSC were then administered either i.v. 1 week before PAC injection or i.p. 3 weeks after to assess their immunomodulatory function on humoral and adaptive immune parameters. Anti-PAC IgM and IgG responses were detected in all PAC-injected rats with a peak at week 2 postinjection and reactivity remaining above baseline levels by week 18. IgG2a and IgG2b were the predominant and long-lasting IgG subtypes. By contrast, no anti-MSC antibody response was detected in the cohort injected with MSC only, but infusion of MSC before PAC injection temporarily augmented the anti-PAC antibody response. Consistent with a cellular immune response to PAC in PAC-injected rats, cytokine/chemokine profiling in serum by antibody array revealed a distinct pattern relative to controls characterized by elevation of multiple markers at week 2, as well as increases in proliferation in draining lymph nodes. Notably, systemic administration of allogeneic MSC under the described conditions did not diminish the immune

  5. Marrow-derived mesenchymal stem cells: role in epithelial tumor cell determination.

    Science.gov (United States)

    Fierro, Fernando A; Sierralta, Walter D; Epuñan, Maria J; Minguell, José J

    2004-01-01

    Marrow stroma represents an advantageous environment for development of micrometastatic cells. Within the cellular structure of marrow stroma, mesenchymal stem cells (MSC) have been postulated as an interacting target for disseminated cancer cells. The studies reported here were performed to gain more information on the interaction of the human breast cancer cell line MCF-7 with human bone marrow-derived MSC cells and to investigate whether this interaction affects tumor cell properties. The results showed that after co-culture with MSC, changes were detected in the morphology, proliferative capacity and aggregation pattern of MCF-7 cells, but these parameters were not affected after the co-culture of MSC cells with a non-tumorigenic breast epithelial cell line, MCF-10. Since the indirect culture of MCF-7 with MSC or its products also resulted in functional changes in the tumor cells, we evaluated whether these effects could be attributed to growth factors produced by MSC cells. It was found that VEGF and IL-6 mimic the effects produced by MSC or its products on the proliferation and aggregation properties of MCF-7, cells, respectively. Thus, it seems that after entry of disseminated tumor cells into the marrow space, their proliferative and morphogenetic organization patterns are modified after interaction with distinct stromal cells and/or with specific signals from the marrow microenvironment.

  6. Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

    Science.gov (United States)

    Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen

    2012-01-01

    Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664

  7. Characterization and Application of a Disposable Rotating Bed Bioreactor for Mesenchymal Stem Cell Expansion

    Directory of Open Access Journals (Sweden)

    Anne Neumann

    2014-11-01

    Full Text Available Recruitment of mesenchymal stromal cells (MSC into the field of tissue engineering is a promising development since these cells can be expanded vivo to clinically relevant numbers and, after expansion, retain their ability to differentiate into various cell lineages. Safety requirements and the necessity to obtain high cell numbers without frequent subcultivation of cells raised the question of the possibility of expanding MSC in one-way (single-use disposable bioreactors. In this study, umbilical cord-derived MSC (UC-MSC were expanded in a disposable Z 2000 H bioreactor under dynamic conditions. Z was characterized regarding residence time and mixing in order to evaluate the optimal bioreactor settings, enabling optimal mass transfer in the absence of shear stress, allowing an reproducible expansion of MSC, while maintaining their stemness properties. Culture of the UC-MSC in disposable Z 2000 H bioreactor resulted in a reproducible 8-fold increase of cell numbers after 5 days. Cells were shown to maintain specific MSC surface marker expression as well as trilineage differentiation potential and lack stress-induced premature senescence.

  8. Characterization and Application of a Disposable Rotating Bed Bioreactor for Mesenchymal Stem Cell Expansion.

    Science.gov (United States)

    Neumann, Anne; Lavrentieva, Antonina; Heilkenbrinker, Alexandra; Loenne, Maren; Kasper, Cornelia

    2014-11-27

    Recruitment of mesenchymal stromal cells (MSC) into the field of tissue engineering is a promising development since these cells can be expanded vivo to clinically relevant numbers and, after expansion, retain their ability to differentiate into various cell lineages. Safety requirements and the necessity to obtain high cell numbers without frequent subcultivation of cells raised the question of the possibility of expanding MSC in one-way (single-use) disposable bioreactors. In this study, umbilical cord-derived MSC (UC-MSC) were expanded in a disposable Z 2000 H bioreactor under dynamic conditions. Z was characterized regarding residence time and mixing in order to evaluate the optimal bioreactor settings, enabling optimal mass transfer in the absence of shear stress, allowing an reproducible expansion of MSC, while maintaining their stemness properties. Culture of the UC-MSC in disposable Z 2000 H bioreactor resulted in a reproducible 8-fold increase of cell numbers after 5 days. Cells were shown to maintain specific MSC surface marker expression as well as trilineage differentiation potential and lack stress-induced premature senescence.

  9. Combination therapy with intra-articular injection of mesenchymal stem cells and articulated joint distraction for repair of a chronic osteochondral defect in the rabbit.

    Science.gov (United States)

    Harada, Yohei; Nakasa, Tomoyuki; Mahmoud, Elhussein Elbadry; Kamei, Goki; Adachi, Nobuo; Deie, Masataka; Ochi, Mitsuo

    2015-10-01

    The present study investigated intra-articular injection of bone-marrow-derived mesenchymal stem cells (MSCs) combined with articulated joint distraction as treatment for osteochondral defects. Large osteochondral defects were created in the weight-bearing area of the medial femoral condyle in rabbit knees. Four weeks after defect creation, rabbits were divided into six groups: control group, MSC group, distraction group, distraction + MSC group, temporary distraction group, and temporary distraction + MSC group. Groups with MSC received intra-articular injection of MSCs. Groups with distraction underwent articulated distraction arthroplasty. Groups with temporary distraction discontinued the distraction after 4 weeks. The rabbits were euthanized at 4, 8, and 12 weeks after treatment except temporary distraction groups which were euthanized at only 12 weeks. Histological scores in the distraction + MSC group were significantly better than in the control, MSC group or distraction group at 4 and 8 weeks, but showed no further improvement. At 12 weeks, the temporary distraction + MSC group showed the best results, demonstrating hyaline cartilage repair with regeneration of the osteochondral junction. In conclusion, joint distraction with intra-articular injection of MSCs promotes early cartilage repair, and compressive loading of the repair tissue after temporary distraction stimulates articular cartilage regeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  10. Identification of Pathways in Liver Repair Potentially Targeted by Secretory Proteins from Human Mesenchymal Stem Cells

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    Sandra Winkler

    2016-07-01

    Full Text Available Background: The beneficial impact of mesenchymal stem cells (MSC on both acute and chronic liver diseases has been confirmed, although the molecular mechanisms behind it remain elusive. We aim to identify factors secreted by undifferentiated and hepatocytic differentiated MSC in vitro in order to delineate liver repair pathways potentially targeted by MSC. Methods: Secreted factors were determined by protein arrays and related pathways identified by biomathematical analyses. Results: MSC from adipose tissue and bone marrow expressed a similar pattern of surface markers. After hepatocytic differentiation, CD54 (intercellular adhesion molecule 1, ICAM-1 increased and CD166 (activated leukocyte cell adhesion molecule, ALCAM decreased. MSC secreted different factors before and after differentiation. These comprised cytokines involved in innate immunity and growth factors regulating liver regeneration. Pathway analysis revealed cytokine-cytokine receptor interactions, chemokine signalling pathways, the complement and coagulation cascades as well as the Januskinase-signal transducers and activators of transcription (JAK-STAT and nucleotide-binding oligomerization domain-like receptor (NOD-like receptor signalling pathways as relevant networks. Relationships to transforming growth factor β (TGF-β and hypoxia-inducible factor 1-α (HIF1-α signalling seemed also relevant. Conclusion: MSC secreted proteins, which differed depending on cell source and degree of differentiation. The factors might address inflammatory and growth factor pathways as well as chemo-attraction and innate immunity. Since these are prone to dysregulation in most liver diseases, MSC release hepatotropic factors, potentially supporting liver regeneration.

  11. How to Hit Mesenchymal Stromal Cells and Make the Tumor Microenvironment Immunostimulant Rather Than Immunosuppressive

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    Alessandro Poggi

    2018-02-01

    Full Text Available Experimental evidence indicates that mesenchymal stromal cells (MSCs may regulate tumor microenvironment (TME. It is conceivable that the interaction with MSC can influence neoplastic cell functional behavior, remodeling TME and generating a tumor cell niche that supports tissue neovascularization, tumor invasion and metastasization. In addition, MSC can release transforming growth factor-beta that is involved in the epithelial–mesenchymal transition of carcinoma cells; this transition is essential to give rise to aggressive tumor cells and favor cancer progression. Also, MSC can both affect the anti-tumor immune response and limit drug availability surrounding tumor cells, thus creating a sort of barrier. This mechanism, in principle, should limit tumor expansion but, on the contrary, often leads to the impairment of the immune system-mediated recognition of tumor cells. Furthermore, the cross-talk between MSC and anti-tumor lymphocytes of the innate and adaptive arms of the immune system strongly drives TME to become immunosuppressive. Indeed, MSC can trigger the generation of several types of regulatory cells which block immune response and eventually impair the elimination of tumor cells. Based on these considerations, it should be possible to favor the anti-tumor immune response acting on TME. First, we will review the molecular mechanisms involved in MSC-mediated regulation of immune response. Second, we will focus on the experimental data supporting that it is possible to convert TME from immunosuppressive to immunostimulant, specifically targeting MSC.

  12. The effect of a chitosan-gelatin matrix and dexamethasone on the behavior of rabbit mesenchymal stem cells

    International Nuclear Information System (INIS)

    Medrado, G C B; Machado, C B; Valerio, P; Sanches, M D; Goes, A M

    2006-01-01

    Cartilage tissue has poor capability of self-repair, especially in the case of severe cartilage damage due to trauma or age-related degeneration. Cell-based tissue engineering using scaffolds has provided an option for the repair of defects in adult cartilage tissue. Mesenchymal stem cells (MSC) and chondrocytes are the two major cell sources for cartilage tissue engineering. The present study combined culture conditions of MSC in a chitosan-gelatin matrix in chondrogenic media to evaluate their effects on MSC viability and chondrogenesis for cartilage tissue engineering. MSC were harvested from rabbit bone marrows and cultured in chondrogenic media supplemented, or not, with dexamethasone in a chitosan-gelatin film (C-GF). The association of C-GF and dexamethasone promoted significant increase in cell adhesivity, viability and proliferation when compared to MCS cultured in media without dexamethasone or C-GF. In addition, dexamethasone promoted increase in the collagen concentration of MSC cultures. A reduction of alkaline phosphatase activity after three weeks of culture in chondrogenic media was verified. No influence of the C-GF or of dexamethasone was observed in this matter. Therefore, it is reasonable to suggest that biomaterial-based chitosan-gelatin and chondrogenic media supplemented with dexamethasone may stimulate the proliferation and differentiation of MSC according to the complex environmental conditions. The information presented here should be useful for the development of biomaterials to regulate the chondrogenesis of MSC suitable for cartilage tissue engineering

  13. Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and Their Extracellular Vesicles: Are We Still Learning?

    Directory of Open Access Journals (Sweden)

    Paul Lohan

    2017-11-01

    Full Text Available Mesenchymal stromal cells (MSC have been used to treat a broad range of disease indications such as acute and chronic inflammatory disorders, autoimmune diseases, and transplant rejection due to their potent immunosuppressive/anti-inflammatory properties. The breadth of their usage is due in no small part to the vast quantity of published studies showing their ability to modulate multiple immune cell types of both the innate and adaptive immune response. While patient-derived (autologous MSC may be the safer choice in terms of avoiding unwanted immune responses, factors including donor comorbidities may preclude these cells from use. In these situations, allogeneic MSC derived from genetically unrelated individuals must be used. While allogeneic MSC were initially believed to be immune-privileged, substantial evidence now exists to prove otherwise with multiple studies documenting specific cellular and humoral immune responses against donor antigens following administration of these cells. In this article, we will review recent published studies using non-manipulated, inflammatory molecule-activated (licensed and differentiated allogeneic MSC, as well as MSC extracellular vesicles focusing on the immune responses to these cells and whether or not such responses have an impact on allogeneic MSC-mediated safety and efficacy.

  14. The effect of stem cell from human exfoliated deciduous teeth on T lymphocyte proliferation.

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    Alipour, Razieh; Adib, Minoo; Hashemi-Beni, Batool; Sadeghi, Farzaneh

    2014-01-01

    Mesenchymal stem cells (MSC), a specific type of adult tissue stem cell; have the immunosuppressive effects that make them valuable targets for regenerative medicine and treatment of many human illnesses. Hence, MSC have been the subject of numerous studies. The classical source of MSC is adult bone marrow (BM). Due to many shortcomings of harvesting MSC from BM, finding the alternative sources for MSC is an urgent. Stem cells from human exfoliated deciduous teeth (SHED) are relative new MSC populations that fulfill these criteria but their potential immunosuppressive effect has not been studied enough yet. Thus, in this work the effect of SHED on the proliferation of in vitro activated T lymphocytes were explored. In this study, both mitogen and alloantigen activated T cells were cultured in the presence of different numbers of SHED. In some co-cultures, activated T cells were in direct contact to MSCs and in other co-cultures; they were separated from SHED by a permeable membrane. In all co-cultures, the proliferation of T cells was measured by ELISA Bromodeoxyuridine proliferation assay. In general, our results showed that SHED significantly suppress the proliferation of activated T cells in a dose-dependent manner. Moreover, the suppression was slightly stronger when MSCs were in physical contact to activated T cells. This study showed that SHED likewise other MSC populations can suppress the activation of T lymphocytes, which can be used instead of BM derived MSCs in many investigational and clinical applications.

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

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    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.

  16. Insulin Promotes the Proliferation of Human Umbilical Cord Matrix-Derived Mesenchymal Stem Cells by Activating the Akt-Cyclin D1 Axis

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    Peng Li

    2017-01-01

    Full Text Available Background. The functions of insulin in mesenchymal stem cells (MSC remain poorly understood. Methods. MSC from human umbilical cord matrix (UCM cultured in serum-free media (SFM with or without insulin were subjected to various molecular biological analyses to determine their proliferation and growth states, expression levels of Akt-cyclin D1 signaling molecules, and in vitro differentiation capacities. Results. Insulin accelerated the G1-S cell cycle progression of UCM-MSC and significantly stimulated their proliferation and growth in SFM. The pro-proliferative action of insulin was associated with augmented cyclin D1 and phosphorylated Akt expression levels. Akt inactivation remarkably abrogated insulin-induced increases in cyclin D1 expression and cell proliferation, indicating that insulin enhances the proliferation of UCM-MSC via acceleration of the G1-S transition mediated by the Akt-cyclin D1 pathway. Additionally, the UCM-MSC propagated in SFM supplemented with insulin exhibited similar specific surface antigen profiles and differentiation capacities as those generated in conventional media containing fetal bovine serum. Conclusions. These findings suggest that insulin acts solely to promote UCM-MSC proliferation without affecting their immunophenotype and differentiation potentials and thus have important implications for utilizing insulin to expand clinical-grade MSC in vitro.

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

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    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.

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

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    Aggerholm-Pedersen, Ninna; Demuth, Christina; Safwat, Akmal; Meldgaard, Peter; Kassem, Moustapha; Sandahl Sorensen, Boe

    2016-01-01

    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.

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

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    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.

  20. Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells

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    Norlaily Mohd Ali

    2016-01-01

    Full Text Available Decline in the therapeutic potential of bone marrow-derived mesenchymal stem cells (MSC is often seen with older donors as compared to young. Although hypoxia is known as an approach to improve the therapeutic potential of MSC in term of cell proliferation and differentiation capacity, its effects on MSC from aged donors have not been well studied. To evaluate the influence of hypoxia on different age groups, MSC from young (60 years donors were expanded under hypoxic (5% O2 and normal (20% O2 culture conditions. MSC from old donors exhibited a reduction in proliferation rate and differentiation potential together with the accumulation of senescence features compared to that of young donors. However, MSC cultured under hypoxic condition showed enhanced self-renewing and proliferation capacity in both age groups as compared to normal condition. Bioinformatic analysis of the gene ontology (GO and KEGG pathway under hypoxic culture condition identified hypoxia-inducible miRNAs that were found to target transcriptional activity leading to enhanced cell proliferation, migration as well as decrease in growth arrest and apoptosis through the activation of multiple signaling pathways. Overall, differentially expressed miRNA provided additional information to describe the biological changes of young and aged MSCs expansion under hypoxic culture condition at the molecular level. Based on our findings, the therapeutic potential hierarchy of MSC according to donor’s age group and culture conditions can be categorized in the following order: young (hypoxia > young (normoxia > old aged (hypoxia > old aged (normoxia.

  1. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

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    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. Mechano-Signal Transduction in Mesenchymal Stem Cells Induces Prosaposin Secretion to Drive the Proliferation of Breast Cancer Cells.

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    Ishihara, Seiichiro; Inman, David R; Li, Wan-Ju; Ponik, Suzanne M; Keely, Patricia J

    2017-11-15

    In response to chemical stimuli from cancer cells, mesenchymal stem cells (MSC) can differentiate into cancer-associated fibroblasts (CAF) and promote tumor progression. How mechanical stimuli such as stiffness of the extracellular matrix (ECM) contribute to MSC phenotype in cancer remains poorly understood. Here, we show that ECM stiffness leads to mechano-signal transduction in MSC, which promotes mammary tumor growth in part through secretion of the signaling protein prosaposin. On a stiff matrix, MSC cultured with conditioned media from mammary cancer cells expressed increased levels of α-smooth muscle actin, a marker of CAF, compared with MSC cultured on a soft matrix. By contrast, MSC cultured on a stiff matrix secreted prosaposin that promoted proliferation and survival of mammary carcinoma cells but inhibited metastasis. Our findings suggest that in addition to chemical stimuli, increased stiffness of the ECM in the tumor microenvironment induces differentiation of MSC to CAF, triggering enhanced proliferation and survival of mammary cancer cells. Cancer Res; 77(22); 6179-89. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Additive effect of mesenchymal stem cells and defibrotide in an arterial rat thrombosis model.

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    Dilli, Dilek; Kılıç, Emine; Yumuşak, Nihat; Beken, Serdar; Uçkan Çetinkaya, Duygu; Karabulut, Ramazan; Zenciroğlu, Ayşegu L

    2017-06-01

    In this study, we aimed to investigate the additive effect of mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral arterial thrombosis. Thirty Sprague Dawley rats were included. An arterial thrombosis model by ferric chloride (FeCl3) was developed in the left femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated (without arterial injury); Group 2-Phosphate buffered saline (PBS) injected; Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT. All had two intraperitoneal injections of 0.5 ml: the 1st injection was 4 h after the procedure and the 2nd one 48 h after the 1st injection. The rats were sacrificed 7 days after the 2nd injection. Although the use of human bone marrow-derived (hBM) hBM-MSC or DFT alone enabled partial resolution of the thrombus, combining them resulted in near-complete resolution. Neovascularization was two-fold better in hBM-MSC + DFT treated rats (11.6 ± 2.4 channels) compared with the hBM-MSC (3.8 ± 2.7 channels) and DFT groups (5.5 ± 1.8 channels) (P < 0.0001 and P= 0.002, respectively). The combined use of hBM-MSC and DFT in a rat model of arterial thrombosis showed additive effect resulting in near-complete resolution of the thrombus.

  4. Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells.

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    Geyh, S; Oz, S; Cadeddu, R-P; Fröbel, J; Brückner, B; Kündgen, A; Fenk, R; Bruns, I; Zilkens, C; Hermsen, D; Gattermann, N; Kobbe, G; Germing, U; Lyko, F; Haas, R; Schroeder, T

    2013-09-01

    Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS-MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS-MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS.

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

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    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. © 2015 Wiley Periodicals, Inc.

  6. The effect of a chitosan-gelatin matrix and dexamethasone on the behavior of rabbit mesenchymal stem cells

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    Medrado, G C B [Medicine School, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Machado, C B [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil); Valerio, P [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil); Sanches, M D [Medicine School, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Goes, A M [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil)

    2006-09-15

    Cartilage tissue has poor capability of self-repair, especially in the case of severe cartilage damage due to trauma or age-related degeneration. Cell-based tissue engineering using scaffolds has provided an option for the repair of defects in adult cartilage tissue. Mesenchymal stem cells (MSC) and chondrocytes are the two major cell sources for cartilage tissue engineering. The present study combined culture conditions of MSC in a chitosan-gelatin matrix in chondrogenic media to evaluate their effects on MSC viability and chondrogenesis for cartilage tissue engineering. MSC were harvested from rabbit bone marrows and cultured in chondrogenic media supplemented, or not, with dexamethasone in a chitosan-gelatin film (C-GF). The association of C-GF and dexamethasone promoted significant increase in cell adhesivity, viability and proliferation when compared to MCS cultured in media without dexamethasone or C-GF. In addition, dexamethasone promoted increase in the collagen concentration of MSC cultures. A reduction of alkaline phosphatase activity after three weeks of culture in chondrogenic media was verified. No influence of the C-GF or of dexamethasone was observed in this matter. Therefore, it is reasonable to suggest that biomaterial-based chitosan-gelatin and chondrogenic media supplemented with dexamethasone may stimulate the proliferation and differentiation of MSC according to the complex environmental conditions. The information presented here should be useful for the development of biomaterials to regulate the chondrogenesis of MSC suitable for cartilage tissue engineering.

  7. Direct Head-To-Head Comparison of Cationic Liposome-Mediated Gene Delivery to Mesenchymal Stem/Stromal Cells of Different Human Sources: A Comprehensive Study

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    Boura, Joana S.; dos Santos, Francisco; Gimble, Jeffrey M.; Cardoso, Carla M.P.; Madeira, Catarina; Cabral, Joaquim M.S.

    2013-01-01

    Abstract Nonviral gene delivery to human mesenchymal stem/stromal cells (MSC) can be considered a very promising strategy to improve their intrinsic features, amplifying the therapeutic potential of these cells for clinical applications. In this work, we performed a comprehensive comparison of liposome-mediated gene transfer efficiencies to MSC derived from different human sources—bone marrow (BM MSC), adipose tissue-derived cells (ASC), and umbilical cord matrix (UCM MSC). The results obtained using a green fluorescent protein (GFP)-encoding plasmid indicated that MSC isolated from BM and UCM are more amenable to genetic modification when compared to ASC as they exhibited superior levels of viable, GFP+ cells 48 hr post-transfection, 58±7.1% and 54±3.8%, respectively, versus 33±4.7%. For all cell sources, high cell recoveries (≈50%) and viabilities (>85%) were achieved, and the transgene expression was maintained for 10 days. Levels of plasmid DNA uptake, as well as kinetics of transgene expression and cellular division, were also determined. Importantly, modified cells were found to retain their characteristic immunophenotypic profile and multilineage differentiation capacity. By using the lipofection protocol optimized herein, we were able to maximize transfection efficiencies to human MSC (maximum of 74% total GFP+ cells) and show that lipofection is a promising transfection strategy for MSC genetic modification, especially when a transient expression of a therapeutic gene is required. Importantly, we also clearly demonstrated that intrinsic features of MSC from different sources should be taken into consideration when developing and optimizing strategies for MSC engineering with a therapeutic gene. PMID:23360350

  8. Different wound healing properties of dermis, adipose, and gingiva mesenchymal stromal cells.

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    Boink, Mireille A; van den Broek, Lenie J; Roffel, Sanne; Nazmi, Kamran; Bolscher, Jan G M; Gefen, Amit; Veerman, Enno C I; Gibbs, Susan

    2016-01-01

    Oral wounds heal faster and with better scar quality than skin wounds. Deep skin wounds where adipose tissue is exposed, have a greater risk of forming hypertrophic scars. Differences in wound healing and final scar quality might be related to differences in mesenchymal stromal cells (MSC) and their ability to respond to intrinsic (autocrine) and extrinsic signals, such as human salivary histatin, epidermal growth factor, and transforming growth factor beta1. Dermis-, adipose-, and gingiva-derived MSC were compared for their regenerative potential with regards to proliferation, migration, and matrix contraction. Proliferation was assessed by cell counting and migration using a scratch wound assay. Matrix contraction and alpha smooth muscle actin was assessed in MSC populated collagen gels, and also in skin and gingival full thickness tissue engineered equivalents (reconstructed epithelium on MSC populated matrix). Compared to skin-derived MSC, gingiva MSC showed greater proliferation and migration capacity, and less matrix contraction in full thickness tissue equivalents, which may partly explain the superior oral wound healing. Epidermal keratinocytes were required for enhanced adipose MSC matrix contraction and alpha smooth muscle actin expression, and may therefore contribute to adverse scarring in deep cutaneous wounds. Histatin enhanced migration without influencing proliferation or matrix contraction in all three MSC, indicating that salivary peptides may have a beneficial effect on wound closure in general. Transforming growth factor beta1 enhanced contraction and alpha smooth muscle actin expression in all three MSC types when incorporated into collagen gels. Understanding the mechanisms responsible for the superior oral wound healing will aid us to develop advanced strategies for optimal skin regeneration, wound healing and scar formation. © 2015 by the Wound Healing Society.

  9. Effects of Mesenchymal Stem Cell Treatment on the Expression of Matrix Metalloproteinases and Angiogenesis during Ischemic Stroke Recovery.

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    Hyo Suk Nam

    Full Text Available The efficacy of mesenchymal stem cell (MSC transplantation in ischemic stroke might depend on the timing of administration. We investigated the optimal time point of MSC transplantation. After MSC treatment, we also investigated the expression of matrix metalloproteinases (MMPs, which play a role in vascular and tissue remodeling.Human bone marrow-derived MSCs (2 × 10(6, passage 5 were administrated intravenously after permanent middle cerebral artery occlusion (MCAO was induced in male Sprague-Dawley rats. First, we determined the time point of MSC transplantation that led to maximal neurological recovery at 1 h, 1 day, and 3 days after MCAO. Next, we measured activity of MMP-2 and MMP-9, neurological recovery, infarction volume, and vascular density after transplanting MSCs at the time that led to maximal neurological recovery.Among the MSC-transplanted rats, those of the MSC 1-hour group showed maximal recovery in the rotarod test (P = 0.023 and the Longa score (P = 0.018. MMP-2 activity at 1 day after MCAO in the MSC 1-hour group was significantly higher than that in the control group (P = 0.002, but MMP-9 activity was not distinct. The MSC 1-hour group also showed smaller infarction volume and higher vascular density than did the control group.In a permanent model of rodent MCAO, very early transplantation of human MSCs (1 h after MCAO produced greater neurological recovery and decreased infraction volume. The elevation of MMP-2 activity and the increase in vascular density after MSC treatment suggest that MSCs might help promote angiogenesis and lead to neurological improvement during the recovery phase after ischemic stroke.

  10. Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

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    P Padmini S J Khedoe

    Full Text Available COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD, and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L mice.Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study or in week 14, 16, 18 and 20 (chronic study. Inflammatory parameters were measured in bronchoalveolar lavage (BAL and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment.These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

  11. Sport-related concussions in New Zealand: a review of 10 years of Accident Compensation Corporation moderate to severe claims and costs.

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    King, Doug; Gissane, Conor; Brughelli, Matt; Hume, Patria A; Harawira, Joseph

    2014-05-01

    This paper provides an overview of the epidemiology of sport-related concussion and associated costs in New Zealand requiring medical treatment from 2001 to 2011 in seven sports codes. A retrospective review of injury entitlement claims by seven sports from 2001 to 2011. Data were analyzed by sporting code, age, ethnicity, gender and year of competition for total and moderate-to-severe (MSC) Accident Compensation Corporation (ACC) claims and costs. A total of 20,902 claims costing $NZD 16,546,026 were recorded over the study period of which 1330 (6.4%) were MSC claims. The mean yearly number and costs of MSC claims were 133 ± 36 and $1,303,942 ± 378,949. Rugby union had the highest number of MSC claims per year (38; 95% CI 36-41 per 1000 MSC claims). New Zealand Māori recorded the highest total ($6,000,759) and mean cost ($21,120) per MSC claim. Although MSC injury claims were only 6.4% of total claims, they accounted for 79.1% of total costs indicating that although the majority of sport-related concussions may be minor in severity, the related economic costs associated with more serious sport-related concussion can be high. The finding that rugby union recorded the most MSC claims in the current study was not unexpected. Of concern is that rugby league recorded a low number of MSC claims but the highest mean cost per claim. Due to the high mean cost per concussion, and the high total and mean cost for New Zealand Māori, further investigation is warranted. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

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

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    Sassoli, Chiara; Nosi, Daniele; Tani, Alessia; Chellini, Flaminia; Mazzanti, Benedetta; Quercioli, Franco; Zecchi-Orlandini, Sandra; Formigli, Lucia

    2014-01-01

    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 + 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

  13. Distinct spatial distribution of microglia and macrophages following mesenchymal stem cell implantation in mouse brain.

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    Le Blon, Debbie; Hoornaert, Chloé; Daans, Jasmijn; Santermans, Eva; Hens, Niel; Goossens, Herman; Berneman, Zwi; Ponsaerts, Peter

    2014-09-01

    Although implantation of cellular material in the central nervous system (CNS) is a key direction in CNS regenerative medicine, this approach is currently limited by the occurrence of strong endogenous immune cell responses. In a model of mesenchymal stem cell (MSC) grafting in the CNS of immune-competent mice, we previously described that MSC grafts become highly surrounded and invaded by Iba1(+) myeloid cells (microglia and/or macrophages). Here, following grafting of blue fluorescent protein (BFP)-expressing MSC in the CNS of CX3CR1(+/-) and CX3CR1(-/-) mice, our results indicate: (1) that the observed inflammatory response is independent of the fractalkine signalling axis, and (2) that a significant spatial distribution of Iba1(+) inflammatory cells occurs, in which Iba1(+) CX3CR1(+) myeloid cells mainly surround the MSC graft and Iba1(+) CX3CR1(-) myeloid cells mainly invade the graft at 10 days post transplantation. Although Iba1(+) CX3CR1(+) myeloid cells are considered to be of resident microglial origin, Iba1(+) CX3CR1(-) myeloid cells are most likely of peripheral monocyte/macrophage origin. In order to confirm the latter, we performed MSC-BFP grafting experiments in the CNS of eGFP(+) bone marrow chimeric C57BL/6 mice. Analysis of MSC-BFP grafts in the CNS of these mice confirmed our observation that peripheral monocytes/macrophages invade the MSC graft and that resident microglia surround the MSC graft site. Furthermore, analysis of major histocompatibility complex class II (MHCII) expression revealed that mainly macrophages, but not microglia, express this M1 pro-inflammatory marker in the context of MSC grafting in the CNS. These results again highlight the complexity of cell implantation immunology in the CNS.

  14. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

    Science.gov (United States)

    Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

    2014-11-01

    Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.

  15. Impact of starting material (fresh versus cryopreserved marrow) on mesenchymal stem cell culture.

    Science.gov (United States)

    Kaplan, Alesia; Sackett, Katie; Sumstad, Darin; Kadidlo, Dianne; McKenna, David H

    2017-09-01

    Mesenchymal stem cells (MSCs) continue to be investigated in multiple clinical trials as potential therapy for different disorders. There is ongoing controversy surrounding the clinical use of cryopreserved versus fresh MSCs. However, little is known about how cryopreservation affects marrow as starting material. The growth kinetics of MSC cultures derived from fresh versus cryopreserved marrow were compared. Data were reviewed on the growth kinetics of MSCs derived from fresh versus cryopreserved marrow of nine donors. Marrow harvested from each donor was separated into four aliquots (one fresh and three cryopreserved for culture). Data on the date of mononuclear cell cryopreservation/thaw, MSC counts at Passages 1 and 2, MSC doubling, MSC fold expansion, viability (of mononuclear cells and final MSCs), and on flow cytometry markers of mononuclear cells and final MSCs were analyzed for the fresh and cryopreserved marrow groups. In total, 21 MSC lots (seven fresh and 14 cryopreserved) were obtained. The average age of cryopreserved mononuclear cell product was 295 days (range, 18-1241 days). There were no significant differences between MSC numbers at Passage 1 (p = 0.1), final MSC numbers (p = 0.5), MSC doubling (p = 0.7), or MSC fold expansion (p = 0.7). A significant difference was observed in viability by flow cytometry for both mononuclear cells (p = 0.002) and final MSCs (p = 0.009), with higher viability in the fresh marrow group. This study demonstrates that MSCs derived from cryopreserved marrow have the same growth characteristics as fresh marrow-derived MSCs. Further studies are needed to explore potential differences in clinical efficacy. © 2017 AABB.

  16. Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model.

    Science.gov (United States)

    Gómez-Mauricio, Guadalupe; Moscoso, Isabel; Martín-Cancho, María-Fernanda; Crisóstomo, Verónica; Prat-Vidal, Cristina; Báez-Díaz, Claudia; Sánchez-Margallo, Francisco M; Bernad, Antonio

    2016-07-16

    Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell- and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model. Pig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry. Intramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1:1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium. The simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.

  17. Evaluation of Effect of Chemical and Organic Fertilizers on Growth Characteristics, Yield and Yield components of three Sesame Ecotypes (Sesamum indicum L.

    Directory of Open Access Journals (Sweden)

    M Goldani

    2014-07-01

    Full Text Available Using organic fertilizers is cause increase soil fertility, improving crop growth and production. For this purpose a greenhouse experiment was carried out in factorial arrangement based on a completely randomized design with three replications during 2011 year. First factor included: three sesame ecotype (MSC3, MSC6, MSC7 and second factor was 6 fertilizer treatments that included: Incorporation manure and chemical fertilizer (216 g manure and 1 gram chemical fertilizer NPK, Chemical fertilizer (2 g NPK, Vermicompost (192 g, Manure ( 228 g, Compost Sulfur granules (192 g per vase and Control (without any manure or fertilizer. Results indicated that different manure treatments had significant effect on morphological and yield components traits, as the most number and length branch per plant was obtained from incorporation manure and chemical fertilizer treatment. Appling incorporation manure and chemical fertilizer treatment had the most biomass in MSC3 ecotype that in comparison of control treatment was increased almost 73 percent. Consuming incorporation manure and chemical fertilizer treatment in MSC3 ecotype was also obtained the most capsule per plant (21.2, number seed per capsule (54.4, 100-seed weight (0.257 g and seed per plant with (1.95 g. The least seed weight per plant with 0.450 g was observed in MSC7 ecotype from application of control treatment. Response of three sesame ecotype (MSC3, MSC6, MSC7 to applied vermin-compost manure was similar; as the amount of seed weight per plant was increased more than 1 g per plant in all these ecotypes and in others fertilizer treatments was not observed this trend. There was significant positive correlation between seed weight per plant and number of capsule per plant (r=0.83**, height (r=0.68** and biomass (r=0.51**. The results showed that incorporation manure and chemical fertilizer was improved on growth and yield characteristics of sesame plant.

  18. Equine platelet lysate as an alternative to fetal bovine serum in equine mesenchymal stromal cell culture - too much of a good thing?

    Science.gov (United States)

    Russell, K A; Koch, T G

    2016-03-01

    Multipotent mesenchymal stromal cells (MSC) are often culture-expanded in vitro. Presently, expansion medium (EM) for MSC is supplemented with fetal bovine serum (FBS). However, increasing cost, variable composition and potential risks associated with bovine antigens call for alternatives. Platelet lysate (PL) has shown promise as an alternative supplement. To determine how equine umbilical cord blood (CB) MSC proliferate in EM enriched with PL or FBS at various concentrations. Randomised dose escalation study. Platelet concentrate was generated from 5 equine whole blood samples through a double centrifugation method and standardised to 1 × 10(12) platelets/l prior to a freeze/thaw cycle to produce PL. Pooled PL or pooled FBS was added to EM at concentrations of 5% to 60%. Proliferation of 4 equine CB-MSC cultures was determined after 4 days using a resazurin semiquantitative assay. Cord blood-MSC proliferated with a dose-dependent response with no significant difference found between PL and FBS up to a 30% concentration. Beyond 30%, proliferation fell in the PL-cultured cells, while continued dose-dependent proliferation was noted in the FBS-cultured cells. Despite reduced cell numbers in high PL concentrations, live/dead staining revealed that adherent cells remained viable. Expansion medium enriched with PL can support short-term equine CB-MSC proliferation at conventional culture concentrations. Based on the unexpected suppression of CB-MSC at higher PL concentrations, an in vivo dose study is indicated to investigate if combinational therapies of CB-MSC and platelet-rich plasma are associated with synergistic or antagonistic effect on CB-MSC function. © 2015 EVJ Ltd.

  19. Human mesenchymal stem cells suppress donor CD4(+) T cell proliferation and reduce pathology in a humanized mouse model of acute graft-versus-host disease.

    Science.gov (United States)

    Tobin, L M; Healy, M E; English, K; Mahon, B P

    2013-05-01

    Acute graft-versus-host disease (aGVHD) is a life-threatening complication following allogeneic haematopoietic stem cell transplantation (HSCT), occurring in up to 30-50% of patients who receive human leucocyte antigen (HLA)-matched sibling transplants. Current therapies for steroid refractory aGVHD are limited, with the prognosis of patients suboptimal. Mesenchymal stem or stromal cells (MSC), a heterogeneous cell population present in many tissues, display potent immunomodulatory abilities. Autologous and allogeneic ex-vivo expanded human MSC have been utilized to treat aGVHD with promising results, but the mechanisms of therapeutic action remain unclear. Here a robust humanized mouse model of aGVHD based on delivery of human peripheral blood mononuclear cells (PBMC) to non-obese diabetic (NOD)-severe combined immunodeficient (SCID) interleukin (IL)-2rγ(null) (NSG) mice was developed that allowed the exploration of the role of MSC in cell therapy. MSC therapy resulted in the reduction of liver and gut pathology and significantly increased survival. Protection was dependent upon the timing of MSC therapy, with conventional MSC proving effective only after delayed administration. In contrast, interferon (IFN)-γ-stimulated MSC were effective when delivered with PBMC. The beneficial effect of MSC therapy in this model was not due to the inhibition of donor PBMC chimerism, as CD45(+) and T cells engrafted successfully in this model. MSC therapy did not induce donor T cell anergy, FoxP3(+) T regulatory cells or cause PBMC apoptosis in this model; however, it was associated with the direct inhibition of donor CD4(+) T cell proliferation and reduction of human tumour necrosis factor-α in serum. © 2012 British Society for Immunology.

  20. Long term beneficial effect of neurotrophic factors-secreting mesenchymal stem cells transplantation in the BTBR mouse model of autism.

    Science.gov (United States)

    Perets, Nisim; Segal-Gavish, Hadar; Gothelf, Yael; Barzilay, Ran; Barhum, Yael; Abramov, Natalie; Hertz, Stav; Morozov, Darya; London, Michael; Offen, Daniel

    2017-07-28

    Autism spectrum disorders (ASD) are neurodevelopmental disabilities characterized by severe impairment in social communication skills and restricted, repetitive behaviors. We have previously shown that a single transplantation of mesenchymal stem cells (MSC) into the cerebral lateral ventricles of BTBR autistic-like mice resulted in an improvement across all diagnostic criteria of ASD. We suggested that brain-derived neurotrophic factor (BDNF), a protein which supports the survival and regeneration of neurons secreted by MSC, largely contributed to the beneficial behavioral effect. In this study, we investigated the behavioral effects of transplanted MSC induced to secrete higher amounts of neurotrophic factors (NurOwn ® ), on various ASD-related behavioral domains using the BTBR mouse model of ASD. We demonstrate that NurOwn ® transplantation had significant advantages over MSC transplantation in terms of improving communication skills, one and six months following treatment, as compared to sham-treated BTBR mice. Furthermore, NurOwn ® transplantation resulted in reduced stereotypic behavior for as long as six months post treatment, compared to the one month improvement observed in the MSC treated mice. Notably, NurOwn ® treatment resulted in improved cognitive flexibility, an improvement that was not observed by MSC treatment. Both MSC and NurOwn ® transplantation induced an improvement in social behavior that lasted for six months. In conclusion, the present study demonstrates that a single transplantation of MSC or NurOwn ® have long-lasting benefits, while NurOwn ® may be superior to MSC treatment. Copyright © 2017. Published by Elsevier B.V.

  1. First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells.

    Science.gov (United States)

    Katagiri, Wataru; Osugi, Masashi; Kawai, Takamasa; Hibi, Hideharu

    2016-01-15

    Secreted growth factors and cytokines in the conditioned medium from bone marrow-derived mesenchymal stem cells (MSC-CM) have several effects on cell behavior. Our previous studies revealed that MSC-CM enhances bone regeneration by increasing cell mobilization, angiogenesis, and osteogenesis in vitro and in vivo. This clinical study was undertaken to evaluate the safety and use of MSC-CM for alveolar bone regeneration in eight patients who were diagnosed as needing bone augmentation prior to dental implant placement. The protocol of this clinical study was approved by the ethics committee of Nagoya University Hospital. MSC-CM was prepared from conditioned medium from commercially available human bone marrow-derived MSCs. Patients were treated with beta-tricalcium phosphate (β-TCP) or an atelocollagen sponge soaked with MSC-CM. Clinical and radiographic assessments were performed during the follow-up period. Histological assessments were also performed in some cases. Clinical and histological data from patients who underwent the SFE procedure without MSC-CM were also used retrospectively as reference controls. MSC-CM contained several cytokines such as insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-β1, and hepatocyte growth factor in relatively low amounts. No systemic or local complications were reported throughout the study. Radiographic evaluation revealed early bone formation in all cases. Histological evaluation also supported the radiographic findings. Furthermore, infiltration of inflammatory cells was scarce throughout the specimens. MSC-CM was used safely and with less inflammatory signs and appears to have great osteogenic potential for regenerative medicine of bone. This is the first in-human clinical study of alveolar bone regeneration using MSC-CM.

  2. 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.

  3. Comparative effects of mesenchymal stem cell therapy in distinct stages of chronic renal failure.

    Science.gov (United States)

    Caldas, Heloisa Cristina; de Paula Couto, Thaís Amarante Peres; Fernandes, Ida Maria Maximina; Baptista, Maria Alice Sperto Ferreira; Kawasaki-Oyama, Rosa Sayoko; Goloni-Bertollo, Eny Maria; Braile, Domingo Marcolino; Abbud-Filho, Mario

    2015-10-01

    The therapeutic potential of adult stem cells in the treatment of chronic diseases is becoming increasingly evident. In the present study, we sought to assess whether treatment with mesenchymal stem cells (MSCs) efficiently retards progression of chronic renal failure (CRF) when administered to experimental models of less severe CRF. We used two renal mass reduction models to simulate different stages of CRF (5/6 or 2/3 mass renal reduction). Renal functional parameters measured were serum creatinine (SCr), creatinine clearance (CCr), rate of decline in CCr (RCCr), and 24-h proteinuria (PT24h). We also evaluated renal morphology by histology and immunohistochemistry. MSCs were obtained from bone marrow aspirates and injected into the renal parenchyma of the remnant kidneys of both groups of rats with CRF (MSC5/6 or MSC2/3). Animals from groups MSC5/6 and CRF2/3 seemed to benefit from MSC therapy because they showed significantly reduction in SCr and PT24h, increase in CCr and slowed the RCCr after 90 days. Treatment reduced glomerulosclerosis but significant improvement did occur in the tubulointerstitial compartment with much less fibrosis and atrophy. MSC therapy reduced inflammation by decreasing macrophage accumulation proliferative activity (PCNA-positive cells) and fibrosis (α-SM-actin). Comparisons of renal functional and morphological parameters responses between the two groups showed that rats MSC2/3 were more responsive to MSC therapy than MSC5/6. This study showed that MSC therapy is efficient to retard CRF progression and might be more effective when administered during less severe stages of CRF.

  4. Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases.

    Science.gov (United States)

    Harrell, C Randall; Simovic Markovic, Bojana; Fellabaum, Crissy; Arsenijevic, Aleksandar; Djonov, Valentin; Arsenijevic, Nebojsa; Volarevic, Vladislav

    2018-05-18

    Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases.MSC-derived exosomes were as efficient as transplanted MSCs in limiting the extent of eye injury and inflammation. Immediately after intravitreal injection, MSC-derived exosomes, due to nano-dimension, diffused rapidly throughout the retina and significantly attenuated retinal damage and inflammation. MSC-derived exosomes successfully delivered trophic and immunomodulatory factors to the inner retina and efficiently promoted survival and neuritogenesis of injured retinal ganglion cells. MSC-derived exosomes efficiently suppressed migration of inflammatory cells, attenuated detrimental Th1 and Th17 cell-driven immune response and ameliorated experimental autoimmune uveitis. MSC-derived exosomes were able to fuse with the lysosomes within corneal cells, enabling delivering of MSC-derived active β-glucuronidase and consequent catabolism of accumulated glycosaminoglycans, indicating their therapeutic potential in the treatment of Mucopolysaccharidosis VII (Sly Syndrome). Importantly, beneficent effects were noticed only in animals that received MSC-derived exosomes and were not seen after therapy with fibroblasts-derived exosomes confirming specific therapeutic potential of MSCs and their products in the treatment of eye diseases.In conclusion, MSC-derived exosomes represent potentially new therapeutic agents in the therapy of degenerative and inflammatory ocular diseases.

  5. Selective interactions between epithelial tumour cells and bone marrow mesenchymal stem cells

    OpenAIRE

    Hombauer, H; Minguell, J J

    2000-01-01

    This work is a comparative study on the features displayed by an epithelial metastatic breast cancer cell line (MCF-7) when set in co-culture with human bone marrow mesenchymal stem cells (MSC) or a feeder layer of 3T3 fibroblasts. MSC, a subset of non-haematopoietic cells in the marrow stroma, display a potential for self-renewal, proliferation and differentiation into precursors for bone, cartilage, connective and muscular tissue. Adhesion of MCF-7 cells to monolayers of MSC or 3T3 was high...

  6. National Aeronautics and Space Administration Manned Spacecraft Center data base requirements study

    Science.gov (United States)

    1971-01-01

    A study was conducted to evaluate the types of data that the Manned Spacecraft Center (MSC) should automate in order to make available essential management and technical information to support MSC's various functions and missions. In addition, the software and hardware capabilities to best handle the storage and retrieval of this data were analyzed. Based on the results of this study, recommendations are presented for a unified data base that provides a cost effective solution to MSC's data automation requirements. The recommendations are projected through a time frame that includes the earth orbit space station.

  7. Comparison of Human Sodium/Iodide Symporter (hNIS) Gene Expressions between Lentiviral and Adenoviral Vectors in Rat Mesenchymal Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, So Yeon; Lee, Won Woo; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Sung Jin; Lee, Heui Ran [Medical Research Center, Seoul National University, Seoul (Korea, Republic of)

    2008-10-15

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirusmediated delivery systems has not been reported. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and transduction efficiency of Rad-hNIS into rMSC evaluated by Rad-GFP was 19.1{+-}4.7%, 54.0{+-}6.4%, 85.7{+-}8.7%, and 98.4{+-}1.3% at MOI 1, 5, 20, and 100, respectively. The hNIS expressions in lenti-hNIS-rMSC or adeno-hNIS-rMSC were assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry and western blot analyses revealed that hNIS expressions in lenti-hNIS-rMSC were greater than those in adeno-hNIS-rMSC at MOI 20 but lower than at MOI 50. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (29,704{+-}6,659 picomole/10{sup 6} cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (6,168{+-}2,134 picomole/10{sup 6} cells). Despite lower amount of expressed protein, hNIS function in rMSC was greater by lentivirus than by adenovirus mediated expression. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative vector efficiency for transgene expression.

  8. From membrane tension to channel gating: A principal energy transfer mechanism for mechanosensitive channels.

    Science.gov (United States)

    Zhang, Xuejun C; Liu, Zhenfeng; Li, Jie

    2016-11-01

    Mechanosensitive (MS) channels are evolutionarily conserved membrane proteins that play essential roles in multiple cellular processes, including sensing mechanical forces and regulating osmotic pressure. Bacterial MscL and MscS are two prototypes of MS channels. Numerous structural studies, in combination with biochemical and cellular data, provide valuable insights into the mechanism of energy transfer from membrane tension to gating of the channel. We discuss these data in a unified two-state model of thermodynamics. In addition, we propose a lipid diffusion-mediated mechanism to explain the adaptation phenomenon of MscS. © 2016 The Protein Society.

  9. Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

    Science.gov (United States)

    Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang; Jiang, Zhi-xin; Chen, Xiao-min

    2015-01-01

    Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed

  10. Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

    Directory of Open Access Journals (Sweden)

    Shuang-shuang Wang

    Full Text Available Formation and progression of atherosclerotic vulnerable plaque (VP is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model.Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP group (n = 10/group and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9 in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6 mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively.Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis

  11. Intravenous infusion umbilical cord-derived mesenchymal stem cell in primary immune thrombocytopenia: A two-year follow-up

    OpenAIRE

    Wang, Xiaohua; Yin, Xiaoguang; Sun, Wei; Bai, Jin; Shen, Yawen; Ao, Qiang; Gu, Yongquan; Liu, Ying

    2017-01-01

    Four patients with chronic refractory immune thrombocytopenic purpura (ITP) received human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The hUC-MSC dose was 5?107 to 1?108. Complete remission (CR) was achieved in three patients in 12 months and one patient in 24 months. Three patients received the second hUC-MSC transplantation with the same dose. The median time between hUC-MSC transplantation and response was 12.5 days (range, 7?16). There were no severe adverse events during a...

  12. The role of vicariance vs. dispersal in shaping genetic patterns in ocellated lizard species in the western Mediterranean

    DEFF Research Database (Denmark)

    Paulo, O. S.; Pinheiro, J.; Miraldo, A.

    2008-01-01

    in the western Mediterranean as exemplified by the distribution of species and subspecies and genetic variation within the ocellated lizard group. To reassess the role of the MSC, partial sequences of three mitochondrial DNA genes (cytochrome b, 12S and 16S ribosomal RNA) and two nuclear genes (beta......-fibrinogen and C-mos) from species of the ocellated lizard group were analysed. Three alternative hypotheses were tested: that divergence was initiated (i) by post-MSC vicariance as the basin filled, (ii) when separate populations established either side of the strait by pre-MSC overseas dispersal, and (iii...

  13. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    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....

  14. Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis.

    Science.gov (United States)

    Zhu, Yu; Wang, Yuchen; Zhao, Bizeng; Niu, Xin; Hu, Bin; Li, Qing; Zhang, Juntao; Ding, Jian; Chen, Yunfeng; Wang, Yang

    2017-03-09

    Osteoarthritis (OA) is the most common joint disease worldwide. In the past decade, mesenchymal stem cells (MSCs) have been used widely for the treatment of OA. A potential mechanism of MSC-based therapies has been attributed to the paracrine secretion of trophic factors, in which exosomes may play a major role. In this study, we aimed to compare the effectiveness of exosomes secreted by synovial membrane MSCs (SMMSC-Exos) and exosomes secreted by induced pluripotent stem cell-derived MSCs (iMSC-Exos) on the treatment of OA. Induced pluripotent stem cell-derived MSCs and synovial membrane MSCs were characterized by flow cytometry. iMSC-Exos and SMMSC-Exos were isolated using an ultrafiltration method. Tunable resistive pulse-sensing analysis, transmission electron microscopy, and western blots were used to identify exosomes. iMSC-Exos and SMMSC-Exos were injected intra-articularly in a mouse model of collagenase-induced OA and the efficacy of exosome injections was assessed by macroscopic, histological, and immunohistochemistry analysis. We also evaluated the effects of iMSC-Exos and SMMSC-Exos on proliferation and migration of human chondrocytes by cell-counting and scratch assays, respectively. The majority of iMSC-Exos and SMMSC-Exos were approximately 50-150 nm in diameter and expressed CD9, CD63, and TSG101. The injection of iMSC-Exos and SMMSC-Exos both attenuated OA in the mouse OA model, but iMSC-Exos had a superior therapeutic effect compared with SMMSC-Exos. Similarly, chondrocyte migration and proliferation were stimulated by both iMSC-Exos and SMMSC-Exos, with iMSC-Exos exerting a stronger effect. The present study demonstrated that iMSC-Exos have a greater therapeutic effect on OA than SMMSC-Exos. Because autologous iMSCs are theoretically inexhaustible, iMSC-Exos may represent a novel therapeutic approach for the treatment of OA.

  15. Bi-directional Activation between Mesenchymal Stem Cells and CLL B-Cells: Implication for CLL Disease Progression

    OpenAIRE

    Ding, Wei; Nowakowski, Grzegorz S.; Knox, Traci R.; Boysen, Justin C.; Maas, Mary L.; Schwager, Susan M.; Wu, Wenting; Wellik, Linda E.; Dietz, Allan B.; Ghosh, Asish K.; Secreto, Charla R.; Medina, Kay L.; Shanafelt, Tait D.; Zent, Clive S.; Call, Timothy G.

    2009-01-01

    It was hypothesized that contact between chronic lymphocytic leukemia (CLL) B-cells and marrow stromal cells impact both cell types. To test this hypothesis, we utilized a long-term primary culture system from bone biopsies that reliably generates a mesenchymal stem cell (MSC). Co-culture of MSC with CLL B-cells protected the latter from both spontaneous apoptosis and drug-induced apoptosis. The CD38 expression in previously CD38 positive CLL B-cells was up-regulated with MSC co-culture. Up-r...

  16. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associated with the utility of MSC-based therapy such as biosafety, immunoprivilege, transfection methods, and distribution in the host. PMID:22530882

  17. Comparison of Human Sodium/Iodide Symporter (hNIS) Gene Expressions between Lentiviral and Adenoviral Vectors in Rat Mesenchymal Stem Cells

    International Nuclear Information System (INIS)

    Park, So Yeon; Lee, Won Woo; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun; Kim, Sung Jin; Lee, Heui Ran

    2008-01-01

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirusmediated delivery systems has not been reported. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and transduction efficiency of Rad-hNIS into rMSC evaluated by Rad-GFP was 19.1±4.7%, 54.0±6.4%, 85.7±8.7%, and 98.4±1.3% at MOI 1, 5, 20, and 100, respectively. The hNIS expressions in lenti-hNIS-rMSC or adeno-hNIS-rMSC were assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry and western blot analyses revealed that hNIS expressions in lenti-hNIS-rMSC were greater than those in adeno-hNIS-rMSC at MOI 20 but lower than at MOI 50. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (29,704±6,659 picomole/10 6 cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (6,168±2,134 picomole/10 6 cells). Despite lower amount of expressed protein, hNIS function in rMSC was greater by lentivirus than by adenovirus mediated expression. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative vector efficiency for transgene expression

  18. Nucleo multiprocessado para aplicações em tempo-real

    OpenAIRE

    Roberto Andre Hexsel

    1988-01-01

    Resumo: Esta Dissertação descreve o nucleo de tempo-real do Multiprocessador para Sistemas de Controle (MSC). O MSC foi desenvolvido no Instituto de Automação do Centro Tecnológico para Informática e possui características que o tornam adequado a aplicações em controle de processos e automação industrial. Estas aplicações exigem respostas rápidas a eventos externos e grande capacidade de processamento. O MSC pode ser configurado para satisfazer as mais diversas aplicações e diferentes níveis ...

  19. Territorio mediático-educativo en Suecia Media education landscape in Sweden

    Directory of Open Access Journals (Sweden)

    María Bergman

    2007-03-01

    Full Text Available Conocer el «territorio mediático educativo» en Suecia, a partir de la perspectiva presentada por la catedrática y pedagoga Birgitta Qvarsell, es el objetivo de este trabajo, que reflexiona sobre la ciencia pedagógica de los medios, «media educology». Basado en el contexto sueco, nos ofrece un análisis global relacionando el impacto y desarrollo de la técnica con los medios de comunicación, reseñando sus influencias en la pedagogía y la educación, contando para ello con todos los actores de este impacto mediático. El trabajo recoge también datos de un reciente informe del Consejo de Medios del Departamento de Cultura sueco, titulado «Los jóvenes y los medios». In this paper we describe the Swedish media education landscape and Brigitta Qvarsell‘s perspective on the influence of technological development in media education in Swedish context. Results of data collection about the media consumption by children and young Swedish people are also included. The conclusion remarks the need for a new area with ethnographic and semiotic basis: media educology.

  20. Building Afghan Research Capability | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The program will combine MSc-level training in South Asia and China for Afghan faculty ... professional and management training for less-qualified faculty members, ... IDRC “unpacks women's empowerment” at McGill University Conference.

  1. FRANKINCENSE AND MYRRH RESOURCES OF ETHIOPIA: I ...

    African Journals Online (AJOL)

    Preferred Customer

    the top export articles of Ethiopia where their export alone ... accelerate economic development in these marginal lands. .... consequences in making identification of source species ...... Ethiopian M.Sc. in Forestry Prgoramme thesis works.

  2. Impacts of climate change, variability and adaptation strategies on ...

    African Journals Online (AJOL)

    hope&shola

    economic development (Majule, 2008). Over 70% of the ... of Gross Net Product and about 66% of total export earnings. ... stantial effects on economic performance and livelihood ...... M.Sc. Dissertation, IRA, Univer. of Dares Salaam, Dares.

  3. Overview of Heart Tumors

    Science.gov (United States)

    ... Tumors By Siddique A. Abbasi, MD, MSc, Assistant Professor of Medicine, Warren Alpert Medical School of Brown University; Attending Cardiologist, Director of Heart Failure, and Director of Cardiac MRI, Providence VA Medical ...

  4. 76 FR 13239 - Notice of Intent to Grant Exclusive License

    Science.gov (United States)

    2011-03-10

    ...: Balance of Shear Stress and Gravity and NASA Case No. MSC- 22859-1 to GNetX Expression, LLC, having its... this published notice, NASA receives written objections including evidence and argument that establish...

  5. 78 FR 47424 - Notice of Intent To Grant Partially Exclusive License

    Science.gov (United States)

    2013-08-05

    ... Proteins: Balance of Shear Stress and Gravity, NASA Case No. MSC-22859-1 to Technology Applications... notice, NASA receives written objections including evidence and argument that establish that the grant of...

  6. Reflective portfolios support learning, personal growth and ...

    African Journals Online (AJOL)

    The Master's degree in Child Health (MSc) and Master's degree in Public. Health (MPH (MCH)) at ... This study involved a qualitative, retrospective record review of .... as fear of confidentiality being breached, distraction from other coursework.

  7. Development of the Young Brain

    Medline Plus

    Full Text Available ... Mental Health Office of Science Policy, Planning, and Communications 6001 Executive Boulevard, Room 6200, MSC 9663 Bethesda, MD ... U.S. Department of Health and Human Services National Institutes of Health USA.gov The ...

  8. Symptoms and Treatment of Depression

    Medline Plus

    Full Text Available ... Mental Health Office of Science Policy, Planning, and Communications 6001 Executive Boulevard, Room 6200, MSC 9663 Bethesda, MD ... U.S. Department of Health and Human Services National Institutes of Health USA.gov The ...

  9. Research Article Special Issue

    African Journals Online (AJOL)

    pc

    2017-11-24

    Nov 24, 2017 ... 3Graduated M.Sc student, babol Noushirvani University of Technology ... during an event [1] and regarded as base motivation for many ... the effects of variation in seismic waves traveling should also be taken into accounts for.

  10. variation of small mammal populations across different habitat types ...

    African Journals Online (AJOL)

    Mwangi

    DIFFERENT HABITAT TYPES IN THE SERENGETI ECOSYSTEM. Flora J. Magige*. Department ... There was moderately high similarity in the number of species caught in the two sites ..... Mountains Tanzania (wet season). MSc. Dissertation ...

  11. Development of the Young Brain

    Medline Plus

    Full Text Available ... When they get stuck in traffic. How they manage their time and their emotions. And this is ... MSC 9663 Bethesda, MD 20892-9663 Follow Us Facebook Twitter YouTube Google Plus NIMH Newsletter NIMH RSS ...

  12. Symptoms and Treatment of Depression

    Medline Plus

    Full Text Available ... Trials Outreach Outreach Home Stakeholder Engagement Outreach Partnership Program Alliance for Research Progress Coalition for Research Progress ... MSC 9663 Bethesda, MD 20892-9663 Follow Us Facebook Twitter YouTube Google Plus NIMH Newsletter NIMH RSS ...

  13. Development of the Young Brain

    Medline Plus

    Full Text Available ... Trials Outreach Outreach Home Stakeholder Engagement Outreach Partnership Program Alliance for Research Progress Coalition for Research Progress ... MSC 9663 Bethesda, MD 20892-9663 Follow Us Facebook Twitter YouTube Google Plus NIMH Newsletter NIMH RSS ...

  14. 78 FR 9711 - Changes in Flood Hazard Determinations

    Science.gov (United States)

    2013-02-11

    ... through the FEMA Map Service Center at www.msc.fema.gov . FOR FURTHER INFORMATION CONTACT: Luis Rodriguez...: Williamson (FEMA City of Brentwood The Honorable Paul L. City Hall, 5211 November 12, 2012 470205 Docket No...

  15. 78 FR 48698 - Changes in Flood Hazard Determinations

    Science.gov (United States)

    2013-08-09

    ... Center at www.msc.fema.gov . FOR FURTHER INFORMATION CONTACT: Luis Rodriguez, Chief, Engineering...- Unincorporated areas The Honorable Paul 711 North Bridge August 14, 2013 555549 1327). of Chippewa County Michels...

  16. 78 FR 29766 - Changes in Flood Hazard Determinations

    Science.gov (United States)

    2013-05-21

    ... Center at www.msc.fema.gov . FOR FURTHER INFORMATION CONTACT: Luis Rodriguez, Chief, Engineering... Department, 06-2751P). Judge, Paul Elizondo 233 North Pecos-La Tower, 101 West Nueva Trinidad Street, Street...

  17. 78 FR 28887 - Changes in Flood Hazard Determinations

    Science.gov (United States)

    2013-05-16

    ... Center at www.msc.fema.gov . FOR FURTHER INFORMATION CONTACT: Luis Rodriguez, Chief, Engineering..., 2013 480035 1290). of Bexar County (12- Wolff, Bexar County Works Department, 06-2065P). Judge, Paul...

  18. Kakodkar, Dr Anil

    Indian Academy of Sciences (India)

    Mumbai), M.Sc. (Nottingham), D.Sc. (h.c.), FNAE, FNASc. Date of birth: 11 November 1943. Specialization: Structural Mechanics and Nuclear Engineering Address: Satish Dhawan Chair of Engineering Eminence, Bhabha Atomic Research Centre, ...

  19. Integrated Geophysical Investigation of the Causes of Road ...

    African Journals Online (AJOL)

    ADOWIE PERE

    failure of the road is caused mainly by geologic sequence and structures such as clayey sub- grade soil under the ... structures and other zones of weakness controlled by regional fractures and ..... Highway Unpublished M.Sc. Project. Obafemi.

  20. NASA preferred reliability-practices for design and test

    Science.gov (United States)

    Lisk, Ronald C.

    1992-01-01

    NASA HQ established the NASA R&M Steering Committee (R&MSC) comprised of membership from each NASA field center. The primary charter of the R&MSC is to obtain, record, and share the best design practices that NASA has applied to successful space flight programs and current design considerations (guidelines) that should enhance flight reliability on emerging programs. The practices and guidelines are being assembled in a living document for distribution to NASA centers and the aerospace community. The document will be updated annually with additional practices and guidelines as contributions from the centers are reviewed and approved by the R&MSC. Practices and guidelines are not requirements, but rather a means of sharing procedures and techniques that a given center and the R&MSC together feel have strong technical merit and application to the design of space-related equipment.

  1. Foundations and implementation of information media on energy, environment and development; Fundamentos e implementacao de midia informativa sobre energia, ambiente e desenvolvimento

    Energy Technology Data Exchange (ETDEWEB)

    Mattozo, Vania A. [Santa Catarina Univ., Florianopolis, SC (Brazil). Programa de Pos-graduacao em Engenharia de Producao. Area de Midia e Conhecimento]. E-mail: vania@ieb.ufsc.br; Camargo, C. Celso Brasil [Santa Catarina Univ., Florianopolis, SC (Brazil). Dept. de Engenharia Eletrica]. E-mail: celso@labplan.ufsc.br; Lage, Nilson Lemos [Santa Catarina Univ., Florianopolis, SC (Brazil). Dept. de Jornalismo]. E-mail: lage@floripa.com.br

    2002-07-01

    This paper discusses the relationship among energy, development and environment. This relationship is the ground for a scientific journalism, performed as a M.Sc. program, for scientific, technological and social questions involving those subjects in the sustainable development discussions.

  2. Symptoms and Treatment of Depression

    Medline Plus

    Full Text Available ... Application Process Managing Grants Clinical Research Training Small Business Research Labs at NIMH Labs at NIMH Home ... Mental Health Office of Science Policy, Planning, and Communications 6001 Executive Boulevard, Room 6200, MSC 9663 Bethesda, ...

  3. Development of the Young Brain

    Medline Plus

    Full Text Available ... Application Process Managing Grants Clinical Research Training Small Business Research Labs at NIMH Labs at NIMH Home ... Mental Health Office of Science Policy, Planning, and Communications 6001 Executive Boulevard, Room 6200, MSC 9663 Bethesda, ...

  4. How Loud Is Too Loud?

    Medline Plus

    Full Text Available ... Your Hearing (infographic) Noise-Induced Hearing Loss Tinnitus Communication Methods & Devices for People With Hearing Loss American ... Into Health ® National Institute on Deafness and Other Communication Disorders 31 Center Drive, MSC 2320, Bethesda, MD ...

  5. 76 FR 23828 - National Institute on Drug Abuse; Notice of Closed Meeting

    Science.gov (United States)

    2011-04-28

    ... unwarranted invasion of personal privacy. Name of Committee: National Institute on Drug Abuse Special Emphasis..., National Institute on Drug Abuse, NIH, DHHS, Room 4227, MSC 9550, 6001 Executive Boulevard, Bethesda, MD....279, Drug Abuse and [[Page 23829

  6. Performance of wastewater treatment plants in Jordan and suitability ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-08-04

    Aug 4, 2008 ... and NH4; therefore it is classified as a strong waste. ... Key words: Wastewater, treatment plants, water reuse, wastewater characteristics, wastewater treatment,. Jordan. ..... MSc. thesis, university of Jordan. Bataineh F, Najjar ...

  7. Physico chemical evaluation of coffee husk, wastes of enset (Enset ...

    African Journals Online (AJOL)

    Vostro 2520

    2016-05-18

    May 18, 2016 ... proportion: 9 kg of vegetable waste treated with 130 g of worms, 9 kg of ... enormous production of solid wastes coupled with poor ..... plant and neem leaves, the amount of carbon to ... MSc thesis (Tropical Land Resource.

  8. THE USE OF CASSAVA SPECIES

    African Journals Online (AJOL)

    User

    The plant is propagated from mature stems, which .... USE OF CASSAVA SPECIES AND ALUM IN WASTE WATER TREATMENT, .... acidity, total suspended solids, dissolved oxygen and ..... Rural Areas, MSc Thesis, Department of Water.

  9. The removal of N and P in aerobic and anoxic-aerobic digestion of ...

    African Journals Online (AJOL)

    When this sludge is thickened to 3–6% total suspended solids (TSS) and digested. (aerobic or .... wastewater treatment plant (Cape Town, South Africa) in 2. 000 ℓ batches ...... MSc thesis, University of Cape Town, Cape. Town, South Africa.

  10. 212__Omoniyi-LOKOJA

    African Journals Online (AJOL)

    User

    environmental laws that borders on proper solid waste and effluent disposals. Key Words: Heavy .... Samples Pre - Treatment. Soil samples from .... bioavailability to plants (Oluyemi et al., 2008). 207 ..... M.Sc. Thesis, Department of. Chemistry ...

  11. Akpen et al.2

    African Journals Online (AJOL)

    PUBLICATIONS1

    from where effluent from Wupa sewage treatment plant is discharged. ... Standards and Regulations Enforcement Agency (NESREA) for waste water. The result indi- .... turbidity, conductivity, total dissolved solids, ..... M.Sc. Thesis, Uni-.

  12. IN SOUTHERN ETHIOPIA

    African Journals Online (AJOL)

    Win7Ent

    2013-06-03

    Jun 3, 2013 ... 1 MSc Research Assistant, School of Food Science and Nutrition, Hawassa ... participant children and mothers preferred the taste of the 10% ... lower quintiles, according to the most recent Demographic and Health Survey [5].

  13. 46 CFR 112.05-1 - Purpose.

    Science.gov (United States)

    2010-10-01

    ...) Other loads may be authorized by the Commanding Officer, Marine Safety Center (MSC), to be connected to... sized to supply these loads using a unity (1.0) service factor; or (2) Be provided with automatic load...

  14. Ectoparasite infestation of free scavenging chickens reared under ...

    African Journals Online (AJOL)

    2009) of which about 99% are raised under the traditional backyard system of management, while 1 ..... including cost effectiveness of control strategies. ... Marketing System of Dale, Wonsho and Loka Abaya Weredas of SNNPRS. MSc thesis ...

  15. Fulltext PDF

    Indian Academy of Sciences (India)

    2011-01-31

    Jan 31, 2011 ... XXVII Refresher Course in Experimental Physics ... about 25 experiments, some at the BSc level and some at the MSc level with a low cost kit ... Course in Experimental Physics has been highly successful and the experiments.

  16. Identification of differentiation-stage specific molecular markers for the osteoblastic phenotype

    DEFF Research Database (Denmark)

    Twine, Natalie; Chen, Li; Wilkins, Marc

    to age-matched control (n=4). Using RNA-seq and cluster analysis, we identified a set of stage-specific molecular markers that define the progression of OB phenotype during ex vivo culture of hMSC, predict in vivo bone formation capacity of hMSC and can be employed to study the mechanisms of impaired......The phenotype of osteoblastic (OB) cells in culture is currently defined using a limited number of markers of low sensitivity and specificity which belong mostly to extracellular matrix proteins. Also, for clinical use of human skeletal (mesenchymal) stem cells (hMSC) in bone regeneration......, there is a need to identify predictive markers for in vivo bone forming capacity. Thus, we employed Illumina RNA sequencing (RNASeq) to examine changes in gene expression across 8 time points between 0-12 days of ex vivo OB differentiation of hMSC. We identified a subset of expressed genes as potentially...

  17. Biological effects of electromagnetic fields

    African Journals Online (AJOL)

    2012-02-28

    Feb 28, 2012 ... radiofrequency emitting sources are radars, mobile phones and their base stations, ... and industrial applications, could have effect on living organisms. ...... Hazards of Electromagnetic Pollution (Msc Thesis). Department of ...

  18. Credit Demand Amongst Farmers in Mukono District, Uganda ...

    African Journals Online (AJOL)

    forming farmers' associations, leveraging mobile money technologies to reduce distance, and streamlining application procedures could bolster agricultural credit demand in Uganda. ...... analysis was collected for the latter's M.Sc. dissertation.

  19. Journal of Agricultural Extension Vol. 17 (1) June, 2013 ISSN 1119 ...

    African Journals Online (AJOL)

    Onyii Ogbonna

    and application of scientific agricultural information for purposeful development of the system (Adebayo ... Internet or mobile phones -- is increasingly bringing market information, financial services, and ..... An M.Sc. Dissertation submitted to the ...

  20. Earth/Mars Landing Impact Attenuation Using Foam

    Data.gov (United States)

    National Aeronautics and Space Administration — Used results from extensive foam testing performed on a previous JSC Innovation Charge Account (ICA) project to develop material models in MSC/Marc commercial finite...