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      Biological properties of extracellular vesicles and their physiological functions

      1 , 2 , * , # , 3 , 4 , * , # , 1 , 2 , 5 , 6 , 7 , 8 , 9 , 10 , 1 , 12 , 13 , 14 , 15 , 16 , 14 , 17 , 18 , 19 , 11 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 21 , 32 , 33 , 34 , 35 , 36 , 23 , 24 , 37 , 38 , 39 , 40 , 36 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 16 , 14 , 15 , 49 , 8 , 50 , 51 , 16 , 52 , 16 , 23 , 24 , 53 , 44 , 54 , 14 , 17 , 23 , 24 , 55 , 46 , 33 , 46 , 14 , 56 , 57 , 46 , 30
      Journal of Extracellular Vesicles
      Co-Action Publishing
      extracellular vesicle, microvesicle, microparticle, exosome, physiology, prokaryote, eukaryote

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          In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

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          Quorum sensing: cell-to-cell communication in bacteria.

          Bacteria communicate with one another using chemical signal molecules. As in higher organisms, the information supplied by these molecules is critical for synchronizing the activities of large groups of cells. In bacteria, chemical communication involves producing, releasing, detecting, and responding to small hormone-like molecules termed autoinducers . This process, termed quorum sensing, allows bacteria to monitor the environment for other bacteria and to alter behavior on a population-wide scale in response to changes in the number and/or species present in a community. Most quorum-sensing-controlled processes are unproductive when undertaken by an individual bacterium acting alone but become beneficial when carried out simultaneously by a large number of cells. Thus, quorum sensing confuses the distinction between prokaryotes and eukaryotes because it enables bacteria to act as multicellular organisms. This review focuses on the architectures of bacterial chemical communication networks; how chemical information is integrated, processed, and transduced to control gene expression; how intra- and interspecies cell-cell communication is accomplished; and the intriguing possibility of prokaryote-eukaryote cross-communication.
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            Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells.

            Adult bone-marrow-derived mesenchymal stem cells are immunosuppressive and prolong the rejection of mismatched skin grafts in animals. We transplanted haploidentical mesenchymal stem cells in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver. Clinical response was striking. The patient is now well after 1 year. We postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo.
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              Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication.

              Normal and malignant cells shed from their surface membranes as well as secrete from the endosomal membrane compartment circular membrane fragments called microvesicles (MV). MV that are released from viable cells are usually smaller in size compared to the apoptotic bodies derived from damaged cells and unlike them do not contain fragmented DNA. Growing experimental evidence indicates that MV are an underappreciated component of the cell environment and play an important pleiotropic role in many biological processes. Generally, MV are enriched in various bioactive molecules and may (i) directly stimulate cells as a kind of 'signaling complex', (ii) transfer membrane receptors, proteins, mRNA and organelles (e.g., mitochondria) between cells and finally (iii) deliver infectious agents into cells (e.g., human immuno deficiency virus, prions). In this review, we discuss the pleiotropic effects of MV that are important for communication between cells, as well as the role of MV in carcinogenesis, coagulation, immune responses and modulation of susceptibility/infectability of cells to retroviruses or prions.

                Author and article information

                J Extracell Vesicles
                J Extracell Vesicles
                Journal of Extracellular Vesicles
                Co-Action Publishing
                14 May 2015
                : 4
                : 10.3402/jev.v4.27066
                [1 ]Unidad de Investigación, Hospital Sta Cristina, Instituto de Investigaciones Sanitarias Princesa (IIS-IP), Madrid, Spain
                [2 ]Departamento de Biología Molecular, UAM, Madrid, Spain
                [3 ]Extracellular Vesicle Research, Division of Biochemistry and Biotechnology, Department of Biosciences, University of Helsinki, Helsinki, Finland
                [4 ]Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
                [5 ]Laboratory for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, Slovenia
                [6 ]IVECAT Group – “Germans Trias i Pujol” Research Institute, Badalona, Spain
                [7 ]Nephrology Service – “Germans Trias i Pujol” University Hospital, Badalona, Spain
                [8 ]Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary
                [9 ]Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary
                [10 ]Faculty of Dentistry, University of Szeged, Szeged, Hungary
                [11 ]Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Spain
                [12 ]Department of Experimental Biomedicine and Clinical Neuroscience, Human Anatomy Section, University of Palermo, Palermo, Italy
                [13 ]Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
                [14 ]Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
                [15 ]Expression Regulation in Cancer, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
                [16 ]Research Unit in Biomedicine and Translational Oncology, Vall Hebron Institute of Research and Autonomous University of Barcelona, Barcelona, Spain
                [17 ]IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
                [18 ]Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
                [19 ]Anti-Tumour Drugs Section, Department of Therapeutic Research and Medicines Evaluation, National Institute of Health (ISS), Rome, Italy
                [20 ]IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
                [21 ]Dana-Farber Cancer Institute, Boston, MA, USA
                [22 ]Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
                [23 ]Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria
                [24 ]Department of Blood Group Serology and Transfusion Medicine, Universitätsklinikum, Salzburger Landeskliniken GesmbH (SALK), Salzburg, Austria
                [25 ]Department of Neurosurgery, University of Colorado Denver, CO, USA
                [26 ]Department of Molecular Biology and Genetics, Thorlab-Therapeutic Oligonucleotide Research Lab, Bilkent University, Ankara, Turkey
                [27 ]Department of Biological Sciences, Middle East Technical University, Ankara, Turkey
                [28 ]Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
                [29 ]Analytical Protein Chemistry, Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark
                [30 ]Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium
                [31 ]Bood Cell Research Group, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
                [32 ]Department of Immunochemistry and Glycobiology, Institute for the Application of Nuclear Energy, INEP, University of Belgrade, Belgrade, Serbia
                [33 ]Laboratory of Clinical Biophysics, Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia
                [34 ]Molecular Cell Biology and Focus Program Translational Neurosciences, University of Mainz, Mainz, Germany
                [35 ]Research and Cell Services, Finnish Red Cross Blood Service, Helsinki, Finland
                [36 ]Krefting Research Centre, Institute of Medicine at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                [37 ]Department of Physiology, Semmelweis University, Budapest, Hungary
                [38 ]Latvian Biomedical Research and Study Centre, Riga, Latvia
                [39 ]Institute of Chemistry and Bioanalytics, School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland
                [40 ]Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital – The Norwegian Radium Hospital, Oslo, Norway
                [41 ]National Institute of Chemistry, Laboratory of Biotechnology, Ljubljana, Slovenia
                [42 ]EN→FIST Centre of Excellence, Ljubljana, Slovenia
                [43 ]Departamento de Biología Celular y Parasitologia, Facultat de Farmacia, Universitat de Valencia, Valencia, Spain
                [44 ]Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
                [45 ]Institute for Environmental Health Sciences and Hospital Infection ControlMedical Center – University of Freiburg, Freiburg im Breisgau, Germany
                [46 ]Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
                [47 ]Institute of Biotechnology, (Viikinkaari 1), University of Helsinki, Helsinki, Finland
                [48 ]School of Pharmacy and Pharmaceutical Sciences & Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
                [49 ]Department of Pathology and Oncology, Faculty of Medicine, University of Porto, Porto, Portugal
                [50 ]ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic – Universitat de Barcelona, Barcelona, Spain
                [51 ]Institució Catalana de Recerca I Estudis Avançats, Barcelona, Spain
                [52 ]Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, and Institut de Recerca Biomèdica de Bellvitge, Barcelona, Spain
                [53 ]Department of Biotechnology Engineering, ORT Braude College, Karmiel, Israel
                [54 ]Servicio de Inmunología, Hospital de la Princesa, Instituto de Investigaciones Sanitarias Princesa (IIS-IP), Madrid, Spain
                [55 ]Departmnet of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
                [56 ]Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
                [57 ]Department of Biological Sciences, Faculty of Pharmacy, University of Porto (FFUP), Porto, Portugal
                Author notes
                [* ]Correspondence to: María Yáñez-Mó Membrane Microdomains in Immunity Laboratory, Unidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa, Departamento de Biología Molecular, UAM, C/Maestro Amadeo Vives 2, edificio consultas 5a planta, ES-28009 Madrid, Spain, Email: maria.yanez@ 123456salud.madrid.org ; maria.yannez@ 123456uam.es ; Pia Siljander, Department of Biosciences, Division of Biochemistry and Biotechnology, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland, Email: pia.siljander@ 123456helsinki.fi
                © 2015 María Yáñez-Mó et al.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 22 December 2014
                : 24 February 2015
                : 10 March 2015
                Review Article

                extracellular vesicle,microvesicle,microparticle,exosome,physiology,prokaryote,eukaryote


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