Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications

Wael Nassar; Mervat El-Ansary; Mostafa Abdel Aziz

doi:doi:10.11648/j.cb.20140206.12

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Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications

Wael Nassar, Mervat El-Ansary, Mostafa Abdel Aziz

Published in Cell Biology (Volume 2, Issue 6)

Received: 29 November 2014 Accepted: 16 December 2014 Published: 22 December 2014

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Abstract

All types of cells of eukaryotic organisms produce and release small Nano-vesicles into their extracellular environment. Early studies have described these vesicles as “garbage bags” only to remove obsolete cellular molecules. Valadi and coworkers, in 2007, was the first who discovered the capability of circulating EVs to horizontally transfer functioning gene information between cells. These extra cellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemo-resistance, genetic exchange and signaling pathway activation through growth factor/receptor transfer. Extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived extracellular vesicles not only to represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we’ll be addressing the characteristics of different types and the clinical relevance of these extracellular EVs and their potentials as diagnostic markers as well as defining therapeutic options.

Published in	Cell Biology (Volume 2, Issue 6)
DOI	10.11648/j.cb.20140206.12
Page(s)	60-71
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2014. Published by Science Publishing Group

Keywords

Extracellular Vesicles (EVs), Exosomes, Horizontal Gene Transfer (HGT), Microvesicles (MVs)

References

[1]	Ochman, H., Lawrence, J.G. and Groisman, E.A. (2000) Lateral gene transfer and the nature of bacterial innovation. Nature, 405, 299–304.
[2]	Walther, W. and Stein, U. (2000) Viral vectors for gene transfer: a review of their use in the treatment of human diseases. Drugs, 60, 249–271.
[3]	Valadi, H. (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol., 9, 654–659.
[4]	Bellingham, S.A. and Hill, A.F. (2012) Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases? Front. Physio., 3, 124.
[5]	Conde-Vancells J, Rodriguez-Suarez E, Embade N, Gil D, Matthiesen R, Valle M, Elortza F, Lu SC, Mato JM, and Falcon-Perez JM (2008) Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 7:5157–5166.
[6]	Morel O, Jesel L, Freyssinet JM, and Toti F (2011) Cellular mechanisms underlying the formation of circulating microparticles. Arterioscler Thromb Vasc Biol 31:15–26.
[7]	Yuana Y, Oosterkamp TH, Bahatyrova S, Ashcroft B, Garcia Rodriguez P, Bertina RM, and Osanto S (2010). Atomic force microscopy: a novel approach to the detection of nanosized blood microparticles. J Thromb Haemost 8:315–323.
[8]	Dragovic RA, Gardiner C, Brooks AS, Tannetta DS, Ferguson DJ, Hole P, Carr B, Redman CW, Harris AL, Dobson PJ, et al. (2011). Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis. Nanomedicine 7:780–788.
[9]	Edwin van der Pol, Anita N. Bo¨ing, Paul Harrison, Augueste Sturk, and Rienk (2012). Classification, Functions, and Clinical Relevance of Extracellular Vesicles. Nieuwland, Pharmacol Rev 64:676–705.
[10]	The´ry C, Ostrowski M, and Segura E (2009). Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581–593.
[11]	Beyer C and Pisetsky DS (2010). The role of microparticles in the pathogenesis of rheumatic diseases. Nat Rev Rheumatol 6:21–29.
[12]	Mathivanan S, Ji H, and Simpson RJ (2010). Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73:1907–1920.
[13]	Yi Lee, Samir EL Andaloussi and Matthew J.A. Wood (2012). Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Human Molecular Genetics, R1–R10.
[14]	Harding,C., Heuser,J. ,and Stahl, P.(1983).Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in ratreticulocytes. J. CellBiol. 97, 329–339.
[15]	Pan,B.T., Blostein,R.,and Johnstone, R. M.(1983). Loss of the transferrin receptor during the maturation of sheep reticulocytes in vitro: an immunological approach. Biochem. J. 210, 37–47.
[16]	Lee Y, El Andaloussi S, Wood MJ (2012): Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet. 21(R1):R125-134.
[17]	Booth AM, Fang Y, Fallon JK, Yang JM, Hildreth JE, and Gould SJ (2006) Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane. J Cell Biol 172:923–935.
[18]	Bobrie A, Colombo M, Raposo G, and The´ry C (2011) Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12:1659–1668.
[19]	Trams, E.G., C.J. Lauter, N. Salem Jr., and U. Heine (1981). Exfoliation of membrane ectoenzymes in the form of micro-vesicles. Biochim. Biophys. Acta. 645:63–70.
[20]	Harding, C., J. Heuser, and P. Stahl. (1984). Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: demonstration of a pathway for receptor shedding. Eur. J. Cell Biol. 35:256 263.
[21]	Pan, B.T., K. Teng, C. Wu, M. Adam, and R.M. Johnstone (1985). Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J. Cell Biol. 101:942–948.
[22]	Raposo, G., H.W. Nijman, W. Stoorvogel, R. Liejendekker, C.V. Harding, C.J. Melief, and H.J. Geuze (1996). B lymphocytes secrete antigenpresenting vesicles. J. Exp. Med. 183:1161–1172.
[23]	Zitvogel, L., A. Regnault, A. Lozier, J. Wolfers, C. Flament, D. Tenza, P. Ricciardi-Castagnoli, G. Raposo, and S. Amigorena. 1998. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat. Med. 4:594–600.
[24]	Aalberts, M., F.M. van Dissel-Emiliani, N.P. van Adrichem, M. van Wijnen, M.H. Wauben, T.A. Stout, and W. Stoorvogel. 2012. Identification of distinct populations of prostasomes that differentially express prostate stem cell antigen, annexin A1, and GLIPR2 in humans. Biol. Reprod. 86:82.
[25]	Théry, C., S. Amigorena, G. Raposo, and A. Clayton. 2006. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol. Chapter 3:Unit 3.22.
[26]	Douglas D. Taylor and Cicek Gercel-Taylor (2013).The origin, function, and diagnostic potential of RNA within extracellular vesicles present in human biological fluids. Frontiers in Genetics.Vol. 4, Article 142.
[27]	Soo, C.Y., Y. Song, Y. Zheng, E.C. Campbell, A.C. Riches, F. Gunn-Moore, and S.J. Powis (2012). Nanoparticle tracking analysis monitors microvesicle and exosome secretion from immune cells. Immunology. 136:192–197.
[28]	Nolte-’t Hoen, E.N., E.J. van der Vlist, M. Aalberts, H.C. Mertens, B.J. Bosch, W. Bartelink, E. Mastrobattista, E.V. van Gaal, W. Stoorvogel, G.J. Arkesteijn, and M.H. Wauben (2012b). Quantitative and qualitative flow cytometric analysis of nanosized cell-derived membrane vesicles. Nanomedicine. 8:712–720.
[29]	Van der Vlist, E.J., E.N. Nolte-’t Hoen, W. Stoorvogel, G.J. Arkesteijn, and M.H. Wauben (2012). Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry. Nat. Protoc. 7:1311–1326.
[30]	Subra, C., K. Laulagnier, B. Perret, and M. Record (2007). Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie. 89:205–212.
[31]	Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends (2013). J Cell Biol. 200: 373-83.
[32]	Ratajczak, J., M. Wysoczynski, F. Hayek, A. Janowska-Wieczorek, and M.Z. Ratajczak (2006). Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia. 20: 1487–1495.
[33]	Valadi, H., K. Ekström, A. Bossios, M. Sjöstrand, J.J. Lee, and J.O. Lötvall (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9:654–659.
[34]	Mittelbrunn, M., C. Gutiérrez-Vázquez, C. Villarroya-Beltri, S. González, F. Sánchez-Cabo, M.A. González, A. Bernad, and F. Sánchez-Madrid (2011). Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun. 2:282.
[35]	Montecalvo, A., A.T. Larregina, W.J. Shufesky, D.B. Stolz, M.L. Sullivan, J.M. Karlsson, C.J. Baty, G.A. Gibson, G. Erdos, Z. Wang, et al (2012). Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood. 119:756–766.
[36]	Nolte-’t Hoen, E.N., H.P. Buermans, M. Waasdorp, W. Stoorvogel, M.H. Wauben, and P.A. ’t Hoen (2012a). Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions. Nucleic Acids Res. 40:9272–9285.
[37]	Giovanni Camussi and Peter J. Quesenberry (2013). Perspectives on the Potential Therapeutic Uses of Vesicles. Exosomes microvesicles, Vol. 1, 6:2013.
[38]	Kalra, H., R.J. Simpson, H. Ji, E. Aikawa, P. Altevogt, P. Askenase, V.C. Bond, F.E. Borràs, X. Breakefield, V. Budnik, et al (2012). Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation.PLoS Biol. 10:e1001450.
[39]	Alberts, Bruce; Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walters (2002). "The Shape and Structure of Proteins". Molecular Biology of the Cell; Fourth Edition. New York and London: Garland Science.
[40]	Bernales, Papa and Walter (2006). Intracellular signaling by the unfolded protein response. Annual Review of Cell and Developmental Biology, 22: 487–508
[41]	Richardson RT, Alekseev OM, Grossman G et al. (July 2006). "Nuclear Autoantigenic Sperm Protein (NASP), a Linker Histone Chaperone That is Required for Cell Proliferation". Journal of Biological Chemistry 281 (30): 21526–34. doi:10.1074/jbc.M603816200. PMID 16728391.
[42]	Ellis RJ (July 2006). "Molecular chaperones: assisting assembly in addition to folding". Trends in Biochemical 1.Sciences 31 (7): 395–401.
[43]	Kris Pauwels and other (2007). "Chaperoning Anfinsen:The Steric Foldases". Molecular Microbiology 64 (4): 917.
[44]	Valapala, M., and Vishwanatha, J.K. (2011). Lipid raft endocytosis and exosomal transport facilitate extracellular trafficking of annexin A2. J. Biol. Chem. 286, 30911–30925.
[45]	Raiborg, C., and H. Stenmark. 2009. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature. 458:445–452.
[46]	Hurley, J.H. (2010). The ESCRT complexes. Crit. Rev. Biochem. Mol. Biol. 45:463–487.
[47]	Peinado H, Lavotshkin S, and Lyden D (2011) The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. Semin Cancer Biol 21:139–146.
[48]	Ostrowski, M., N.B. Carmo, S. Krumeich, I. Fanget, G. Raposo, A. Savina, C.F. Moita, K. Schauer, A.N. Hume, R.P. Freitas, et al. (2010). Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 12:19–30.
[49]	Cai, H., K. Reinisch, and S. Ferro-Novick. (2007). Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle. Dev. Cell. 12:671–682.
[50]	Xu, C; et al (2005). "Endoplasmic Reticulum Stress: Cell Life and Death Decisions". J. Clin. Invest 115 (10): 2656–2664.
[51]	Kober L, Zehe C, Bode J (October 2012). "Development of a novel ER stress based selection system for the isolation of highly productive clones". Biotechnol. Bioeng. 109 (10): 2599–611.
[52]	Bellingham, S.A., B.M. Coleman, and A.F. Hill. (2012). Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells. Nucleic Acids Res. 40:10937–10949
[53]	Nolte-’t Hoen, E.N., H.P. Buermans, M. Waasdorp, W. Stoorvogel, M.H. Wauben, and P.A. ’t Hoen. (2012a). Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions. Nucleic Acids Res. 40:9272–9285.
[54]	Levine AJ (1997). p53, the cellular gatekeeper for growth and division. Cell; 88:323–31.
[55]	Jin S, Levine AJ (2001). The p53 functional circuit. J Cell Sci; 114:4139–40.
[56]	Snyder AR (2004). Review of radiation-induced bystander effects. Hum Exp Toxicol; 23:87–9.
[57]	Azzam EI, Little JB (2004). The radiation-induced bystander effect: evidence and significance. Hum Exp Toxicol ; 23:61–5.
[58]	Goldberg Z, Lehnert BE (2002). Radiation-induced effects in unirradiated cells: a review and implications in cancer. Int J Oncol; 21:337–49.
[59]	Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ (2000). Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci; 113:3365–74.
[60]	Passer BJ, Nancy-Portebois V, Amzallag N, et al (2003). The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase. Proc Natl Acad Sci U S A; 100:2284–9.
[61]	Xu, C; et al (2005). "Endoplasmic Reticulum Stress: Cell Life and Death Decisions". J. Clin. Invest 115 (10): 2656–2664.
[62]	Gercel-Taylor, C., Tullis, R. H., Atay, S., Kesimer, M., and Taylor, DD (2012).Nano particle analysis of circulating cell-derived vesicles in ovarian cancer patients. Anal. Biochem. 428, 44–53.
[63]	Buschow, S.I., E.N. Nolte-’t Hoen, G. van Niel, M.S. Pols, T. ten Broeke, M. Lauwen, F. Ossendorp, C.J. Melief, G. Raposo, R. Wubbolts, et al. (2009). MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. Traffic. 10:1528–1542.
[64]	Rana, S., S. Yue, D. Stadel, and M. Zöller (2012). Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection. Int. J. Biochem. Cell Biol. 44:1574–1584
[65]	Laura Ann Mulcahy, Ryan Charles Pink and David Raul Francisco Carter (2014). Routes and mechanisms of extracellular vesicle uptake. Journal of Extracellular Vesicles 2014, 3: 24641.
[66]	Hong BS, Cho JH, Kim H, Choi EJ, Rho S, Kim J, Kim JH, Choi DS, Kim YK, Hwang D, et al. (2009) Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 10:556.
[67]	Xiang X, Poliakov A, Liu C, Liu Y, Deng ZB, Wang J, Cheng Z, Shah SV, Wang GJ, Zhang L, et al. (2009) Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer 124:2621–2633.
[68]	Corrado, C., Raimondo,S., Chiesi, A., Ciccia,F., DeLeo,G., and Alessandro, R.(2013). Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications. Int. J. Mol.Sci. 14, 5338–5366.
[69]	Ji, H.,Greening,D.W., Barnes, T.W., Lim, J.W.,Tauro, B.J.,Rai, A., et al.(2013). Proteome profiling of exosomes derived from human primary and metastatic colorectal cells reveal differential expression of key metastatic factors and signal transduction components. Proteomics 13, 1672–1686.
[70]	Quah, B.J.,andO’Neill,H.C. (2005). Maturation of function in dendritic cells for tolerance and immunity. J. Cell. Mol. Med. 9, 643–654.
[71]	Lewis,C.E., and Pollard, J.W.(2006). Distinct role of macrophages in different tumor micro environments. Cancer Res. 66, 605–612.
[72]	Whiteside, T.L (2013). Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour derived exosomes). Biochem. Soc. Trans. 41, 245–251.
[73]	Ivannikov, M. et al. (2013). "Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume". J. Mol. Neurosci. 49 (1): 223–230.
[74]	The´ry C, Ostrowski M, and Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581–593.
[75]	Connor DE, Exner T, Ma DD, and Joseph JE (2010) The majority of circulating platelet-derived microparticles fail to bind annexin V, lack phospholipid dependent procoagulant activity and demonstrate greater expression of glycoproteinIb. Thromb Haemost 103:1044–1052.
[76]	Giovanni Camussi and Peter J. Quesenberry (2013). Perspectives on the Potential Therapeutic Uses of Vesicles. Exosomes microvesicles, Vol. 1, 6.
[77]	Pan, B.T., Blostein, R., and Johnstone, R. M.(1983). Loss of the transferrin receptor during the maturation of sheep reticulocytes in vitro: an immunological approach. Biochem. J. 210, 37–47.
[78]	Johnstone, R.M., Adam, M., Hammond, J.R., Orr, L., and Turbide, C.(1987).Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 262, 9412–9420.
[79]	Corrado,C., Raimondo, S., Chiesi, A., Ciccia, F., DeLeo, G.,and Alessandro,R. (2013). Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications. Int. J. Mol. Sci. 14, 5338–5366.
[80]	Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito A, et al (2009). Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem; 284: 34211-34222,
[81]	Hong BS, Cho JH, Kim H, Choi EJ, Rho S, Kim J, Kim JH, Choi DS, Kim YK, Hwang D, et al. (2009). Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 10:556.
[82]	Xiang X, Poliakov A, Liu C, Liu Y, Deng ZB, Wang J, Cheng Z, Shah SV, Wang GJ, Zhang L, et al. (2009) Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer 124:2621–2633.
[83]	Whiteside, T.L.(2013). Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour derived exosomes). Biochem. Soc. Trans. 41, 245–251.
[84]	The´ry C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, and Amigorena S (1999) Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol 147:599–610.
[85]	Clayton A, Harris CL, Court J, Mason MD, and Morgan BP (2003) Antigenpresenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. Eur J Immunol 33:522–531.
[86]	Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, and Geuze HJ (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183:1161–1172.
[87]	Atay, S.,Gercel-Taylor,C., Kesimer, M., and Taylor, D.D.(2011a). Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells. Exp.CellRes. 317, 1192–1202.
[88]	Martínez-Lorenzo MJ, Anel A, Gamen S, Monle n I, Lasierra P, Larrad L, Pin˜ eiro A, Alava MA, and Naval J (1999) Activated human T cells release bioactive Fas ligand and APO2 ligand in microvesicles. J Immunol 163:1274–1281.
[89]	Abrahams VM, Straszewski-Chavez SL, Guller S, and Mor G (2004) First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol Hum Reprod 10:55–63.
[90]	Fra¨ngsmyr L, Baranov V, Nagaeva O, Stendahl U, Kjellberg L, and Mincheva- Nilsson L (2005) Cytoplasmic microvesicular form of Fas ligand in human early placenta: switching the tissue immune privilege hypothesis from cellular to vesicular level. Mol Hum Reprod 11:35–41.
[91]	Abrahams VM, Straszewski SL, Kamsteeg M, Hanczaruk B, Schwartz PE, Rutherford TJ, and Mor G (2003) Epithelial ovarian cancer cells secrete functional Fas ligand. Cancer Res 63:5573–5581.
[92]	Clayton A, Mitchell JP, Court J, Linnane S, Mason MD, and Tabi Z (2008) Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol 180: 7249–7258.
[93]	Almqvist N, Lo¨nnqvist A, Hultkrantz S, Rask C, and Telemo E (2008) Serum-derived exosomes from antigen-fed mice prevent allergic sensitization in a model of allergic asthma. Immunology 125:21–27.
[94]	Korpos, E., Kadri, N., Kappelhoff, R., et al. (2013) The Peri-Islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human. Diabetes, 62, 531-542.
[95]	Flanagan J, Middeldorp J, and Sculley T (2003) Localization of the Epstein-Barr virus protein LMP 1 to exosomes. J Gen Virol 84:1871–1879.
[96]	van Niel G, Raposo G, Candalh C, Boussac M, Hershberg R, Cerf-Bensussan N, and Heyman M (2001) Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 121:337–349.
[97]	Van Niel G, Mallegol J, Bevilacqua C, Candalh C, Brugie`re S, Tomaskovic-Crook E, Heath JK, Cerf-Bensussan N, and Heyman M (2003) Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice. Gut 52:1690–1697.
[98]	Segura E, Gue´rin C, Hogg N, Amigorena S, and The´ry C (2007) CD8_ dendritic cells use LFA-1 to capture MHC-peptide complexes from exosomes in vivo. J Immunol 179:1489–1496.
[99]	Muntasell, A.; Berger, A.C.; Roche, P.A (2007). T cell-induced secretion of mhc class II-peptide complexes on b cell exosomes EMBO J., 26, 4263–4272.
[100]	Zitvogel, L.; Regnault, A.; Lozier, A.; Wolfers, J.; Flament, C.; Tenza, D.; Ricciardi-Castagnoli, P.; Raposo, G.; Amigorena, S (1998). Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell-derived exosomes. Nat. Med., 4, 594–600.
[101]	Rautou PE, Leroyer AS, Ramkhelawon B, Devue C, Duflaut D, Vion AC, Nalbone G, Castier Y, Leseche G, Lehoux S, et al. (2011) Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration. Circ Res 108:335–343.
[102]	Yong Zhao, Zhaoshun Jiang and Chengshan Guo (2011). New hope for type 2 diabetics: Targeting insulin resistance through the immune modulation of stem cells. Autoimmunity Reviews 11, 137–142.
[103]	Feng D, Zhao WL, Ye YY, Bai XC, Liu RQ, Chang LF, et al(2010). Cellular internalization of exosomes occurs through phagocytosis. Traffic; 11: 675-687.
[104]	Boilard E, Nigrovic PA, Larabee K, Watts GF, Coblyn JS, Weinblatt ME, Massarotti EM, Remold-O’Donnell E, Farndale RW, Ware J, et al. (2010) Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 327:580–583
[105]	Bruggmann P, et al.; Swiss Hepatitis C Cohort Study (2008) Active intravenous drug use during chronic hepatitis C therapy does not reduce sustained virological response rates in adherent patients. J Viral Hepat 15(10):747–752.
[106]	Fafi-Kremer S, et al. (2010) Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation. J Exp Med 207(9):2019– 2031.
[107]	Rashad S. Barsoum (2007) Hepatitis C virus: from entry to renal injury—facts and potentials Nephrol. Dial. Transplant.2 2 (7): 1840-1848
[108]	Lenassi M, et al. (2010) HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic 11(1):110–122.
[109]	Park IW and He JJ (2010) HIV-1 is budded from CD4 T lymphocytes independently of exosomes. Virol J 7:234
[110]	Feng Z, et al. (2013) A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. Nature 496(7445):367–371.
[111]	Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Wu¨ rdinger T, and Middeldorp JM (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA 107:6328–6333.
[112]	Meckes DG Jr, Shair KH, Marquitz AR, Kung CP, Edwards RH, and Raab-Traub N (2010) Human tumor virus utilizes exosomes for intercellular communication. Proc Natl Acad Sci USA 107:20370–20375
[113]	Meckes DG Jr, Shair KH, Marquitz AR, Kung CP, Edwards RH, and Raab-Traub N (2010) Human tumor virus utilizes exosomes for intercellular communication. Proc Natl Acad Sci USA 107:20370–20375.
[114]	Meckes DG Jr and Raab–Traub N (2011) Microvesicles and viral infection. J Virol 85:12844–12854
[115]	Chiara Corrado, Stefania Raimondo, Antonio Chiesi, Francesco Ciccia, Giacomo De Leo, and Riccardo Alessandro (2013) Exosomes as Intercellular Signaling Organelles Involved in Health and Disease: Basic Science and Clinical Applications. Int. J. Mol. Sci. 14, 5338-5366
[116]	Nelson, PN; Hooley, P and Molecular Immunology Research Group (October 2004).”Human endogenous retroviruses: Transposable elements with potential?”.Clinical and Experimental Immunology 138 (138(1)): 1–9.
[117]	Dino Demirovic, Suresh I.S. Rattan (2013). Establishing cellular stress response profiles as biomarkers of homeodynamics, health and hormesis. Experimental Gerontology, 48; 94-98.
[118]	Park JE, Tan HS, Datta A, Lai RC, Zhang H, Meng W, Lim SK, and Sze SK (2010) Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol Cell Proteomics 9:1085–1099.
[119]	Tourneur L, Mistou S, Schmitt A, and Chiocchia G (2008) Adenosine receptors control a new pathway of Fas-associated death domain protein expression regulation by secretion. J Biol Chem 283:17929–17938.
[120]	Ciravolo V, Huber V, Ghedini GC, Venturelli E, Bianchi F, Campiglio M, Morelli D, Villa A, Della Mina P, Menard S, et al. (2012) Potential role of HER2- overexpressing exosomes in countering trastuzumab-based therapy. J Cell Physiol 227:658–667.
[121]	Gong J, Jaiswal R, Mathys JM, Combes V, Grau GE, and Bebawy M (2012) Microparticles and their emerging role in cancer multidrug resistance. Cancer Treat Rev 38:226–234.
[122]	Hakulinen J, Sankkila L, Sugiyama N, Lehti K, and Keski-Oja J (2008) Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular exosomes. J Cell Biochem 105:1211–1218.
[123]	Uno K, Homma S, Satoh T, Nakanishi K, Abe D, Matsumoto K, Oki A, Tsunoda H, Yamaguchi I, Nagasawa T, et al. (2007) Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer. Br J Cancer 96:290–295.
[124]	Uno K, Homma S, Satoh T, Nakanishi K, Abe D, Matsumoto K, Oki A, Tsunoda H, Yamaguchi I, Nagasawa T, et al. (2007) Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer. Br J Cancer 96:290–295.
[125]	Chargaff E and West R (1946) The biological significance of the thromboplastic protein of blood. J Biol Chem 166:189–197.
[126]	Wolf P (1967) The nature and significance of platelet products in human plasma. Br J Haematol 13:269–288.
[127]	Selkoe, D.J. (2001). Alzheimer’s disease results from the cerebral accumulation and cytotoxicity of amyloid beta-protein. J. Alzheimers Dis. 3, 75–80.
[128]	Rajendran, L.; Honsho, M.; Zahn, T.R.; Keller, P.; Geiger, K.D.; Verkade, P.; Simons, K (2006). Alzheimer’s disease b-amyloid peptides are released in association with exosomes. Proc. Natl. Acad. Sci. USA, 103, 11172–11177.
[129]	Alvarez-Erviti, L.S.Y.; Schapira, A.H.; Gardiner, C.; Sargent, I.L.; Wood, M.J.; Cooper, J.M (2011). Lysosomal dys-function increases exosome-mediated alpha-synuclein release and transmission. Neurobiol. Dis. 42, 360–367.
[130]	Surgucheva, I.; Sharov, V.; Surguchov, A. Γ-synuclein (2012): Seeding of α-synuclein aggregation andtransmission between cells. Biochemistry, 51, 4743–4754.
[131]	Saman, S.; Kim, W.; Raya, M.; Visnick, Y.; Miro, S.; Saman, S.; Jackson, B.; McKee, A.; Alvarez, V.; Lee, N.; et al (2012). Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early alzheimer disease. J. Biol. Chem. 287, 3842–3849.
[132]	Kuwabara, Y.; Ono, K.; Horie, T.; Nishi, H.; Nagao, K.; Kinoshita, M.; Watanabe, S.; Baba, O.; Kojima, Y.; Shizuta, S.; et al (2011). Increased microrna-1 and microrna-133a levels in serum of patientswith cardiovascular disease indicate myocardial damage. Circ. Cardiovasc. Genet. 4, 446–454.
[133]	Azevedo, L.; Janiszewski, M.; Pontieri, V.; Pedro, A.; Bassi, E.; Tucci, P.; Laurindo, F (2007). Platelet-derived exosomes from septic shock patients induce myocardial dysfunction. Crit. Care, 11, R120.
[134]	Hergenreider, E.; Heydt, S.; Treguer, K.; Boettger, T.; Horrevoets, A.J.; Zeiher, A.M.; Scheffer, M.P.; Frangakis, A.S.; Yin, X.; Mayr, M.; et al. Atheroprotective communication between endothelial cells and smooth muscle cells through mirnas. Nat. Cell Biol. 2012, 14, 249–256.
[135]	Zhang, H.; Liu, C.; Su, K.; Yu, S.; Zhang, L.; Zhang, S.; Wang, J.; Cao, X.; Grizzle, W.; Kimberly, R (2006). A membrane form of TNF-α presented by exosomes delays T cell activation-induced cell death. J. Immunol. 176, 7385–7393.
[136]	Martinez-Lostao, L.; García-Alvarez, F.; Basáñez, G.; Alegre-Aguarón, E.; Desportes, P.; Larrad, L.; Naval, J.; Martínez-Lorenzo, M.J.; Anel, A (2010). Liposome-bound apo2l/trail is an effective treatment in a rabbit model of rheumatoid arthritis. Arthritis Rheum. 62, 2272–2282.
[137]	Edwin van der Pol, Anita N. Bo¨ing, Paul Harrison, Augueste Sturk, and Rienk (2012) Classification, Functions, and Clinical Relevance of Extracellular Vesicles. Nieuwland, Pharmacol Rev 64:676–705.
[138]	Liang, B., Peng, P., Chen, S., Li, L., Zhang, M.,Cao, D., et al. (2013). Characterization and proteomic analysis of ovarian cancer-derived exosomes. J. Proteomics 80C,171–182.
[139]	Takeshita,N.,Hoshino,I., Mori,M., Akutsu,Y., Hanari, N.,Yoneyama, Y., et al. (2013).Serum microRNA expression profile: miR-1246 as a novel diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma. Br.J.Cancer 108, 644–652.
[140]	Mitchell, P.S., Parkin, R.K., Kroh, E.M., Fritz, B.R., Wyman, S.K., Pogosova-Agadjanyan, E.L.,et al. (2008). Circulating microRNAs as stable blood-based markers for cancer detection. Proc.Natl.Acad. Sci.U.S.A. 105, 10513–10518.
[141]	Saman S, Kim W, Raya M, Visnick Y, Miro S, Saman S, Jackson B, McKee AC, Alvarez VE, Lee NC, et al. (2012) Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J Biol Chem 287:3842–3849
[142]	Mathivanan, S.; Simpson, R.J. (2009) Exocarta: A compendium of exosomal proteins and RNA. Proteomics, 9, 4997–5000.
[143]	Kalra, H.; Simpson, R.; Ji, H.; Aikawa, E.; Altevogt, P.; Askenase, P.; Bond, V.C.; Borràs, F.E.; Breakefield, X.; Budnik, V.; et al (2012). Vesiclepedia: A compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 10, e1001450.
[144]	El-Andaloussi, S.; Lee, Y.; Lakhal-Littleton, S.; Li, J.; Seow, Y.; Gardiner, C.; Alvarez-Erviti, L.; Sargent, I.L.; Wood, M.J. (2012). Exosome-mediated delivery of sirna in vitro and in vivo. Nat. Protoc. 7, 2112–2126.
[145]	Ohno, S.; Takanashi, M.; Sudo, K.; Ueda, S.; Ishikawa, A.; Matsuyama, N.; Fujita, K.; Mizutani, T.; Ohgi, T.; Ochiya, T.; et al (2013). Systemically injected exosomes targeted to egfr deliver antitumor microrna to breast cancer cells. Mol. Ther. 21, 185–191.
[146]	Ratajczak J, Miekus K, Kucia M et al. (2006). Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia; 20: 847–856.
[147]	Camussi G, Deregibus MC, Bruno S et al. (2010) Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int; 78: 838–848
[148]	Luigi Biancone, Stefania Bruno, Maria Chiara Deregibus, Ciro Tetta and Giovanni Camussi (2012). Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol Dial Transplant (2012) 27: 3037–3042.
[149]	Schwanhäusser B, Busse D, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M. (2013). "Corrigendum: Global quantification of mammalian gene expression control". Nature, 495 (7439): 126–7.
[150]	Wang K, Zhang S, Weber J, Baxter D, Galas DJ. (2010). Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res. 38: 7248-59.

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Wael Nassar, Mervat El-Ansary, Mostafa Abdel Aziz. (2014). Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications. Cell Biology, 2(6), 60-71. https://doi.org/10.11648/j.cb.20140206.12

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Wael Nassar; Mervat El-Ansary; Mostafa Abdel Aziz. Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications. Cell Biol. 2014, 2(6), 60-71. doi: 10.11648/j.cb.20140206.12

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Wael Nassar, Mervat El-Ansary, Mostafa Abdel Aziz. Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications. Cell Biol. 2014;2(6):60-71. doi: 10.11648/j.cb.20140206.12

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@article{10.11648/j.cb.20140206.12,
  author = {Wael Nassar and Mervat El-Ansary and Mostafa Abdel Aziz},
  title = {Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications},
  journal = {Cell Biology},
  volume = {2},
  number = {6},
  pages = {60-71},
  doi = {10.11648/j.cb.20140206.12},
  url = {https://doi.org/10.11648/j.cb.20140206.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cb.20140206.12},
  abstract = {All types of cells of eukaryotic organisms produce and release small Nano-vesicles into their extracellular environment. Early studies have described these vesicles as “garbage bags” only to remove obsolete cellular molecules. Valadi and coworkers, in 2007, was the first who discovered the capability of circulating EVs to horizontally transfer functioning gene information between cells. These extra cellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemo-resistance, genetic exchange and signaling pathway activation through growth factor/receptor transfer. Extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived extracellular vesicles not only to represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we’ll be addressing the characteristics of different types and the clinical relevance of these extracellular EVs and their potentials as diagnostic markers as well as defining therapeutic options.},
 year = {2014}
}

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TY  - JOUR
T1  - Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications
AU  - Wael Nassar
AU  - Mervat El-Ansary
AU  - Mostafa Abdel Aziz
Y1  - 2014/12/22
PY  - 2014
N1  - https://doi.org/10.11648/j.cb.20140206.12
DO  - 10.11648/j.cb.20140206.12
T2  - Cell Biology
JF  - Cell Biology
JO  - Cell Biology
SP  - 60
EP  - 71
PB  - Science Publishing Group
SN  - 2330-0183
UR  - https://doi.org/10.11648/j.cb.20140206.12
AB  - All types of cells of eukaryotic organisms produce and release small Nano-vesicles into their extracellular environment. Early studies have described these vesicles as “garbage bags” only to remove obsolete cellular molecules. Valadi and coworkers, in 2007, was the first who discovered the capability of circulating EVs to horizontally transfer functioning gene information between cells. These extra cellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemo-resistance, genetic exchange and signaling pathway activation through growth factor/receptor transfer. Extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived extracellular vesicles not only to represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we’ll be addressing the characteristics of different types and the clinical relevance of these extracellular EVs and their potentials as diagnostic markers as well as defining therapeutic options.
VL  - 2
IS  - 6
ER  -

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Author Information

Wael Nassar

Department of Nephrology, Sahel Teaching Hospital, General Organization of Teaching Hospitals and Institutes (GOTHI), Cairo, Egypt
Mervat El-Ansary

Department of Clinical Pathology, Stem Cell Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
Mostafa Abdel Aziz

Department of Nephrology, Kidney Transplantation Unit, October Six University Hospitals, Cairo, Egypt

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APA Style

Wael Nassar, Mervat El-Ansary, Mostafa Abdel Aziz. (2014). Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications. Cell Biology, 2(6), 60-71. https://doi.org/10.11648/j.cb.20140206.12

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ACS Style

Wael Nassar; Mervat El-Ansary; Mostafa Abdel Aziz. Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications. Cell Biol. 2014, 2(6), 60-71. doi: 10.11648/j.cb.20140206.12

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AMA Style

Wael Nassar, Mervat El-Ansary, Mostafa Abdel Aziz. Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications. Cell Biol. 2014;2(6):60-71. doi: 10.11648/j.cb.20140206.12

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@article{10.11648/j.cb.20140206.12,
  author = {Wael Nassar and Mervat El-Ansary and Mostafa Abdel Aziz},
  title = {Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications},
  journal = {Cell Biology},
  volume = {2},
  number = {6},
  pages = {60-71},
  doi = {10.11648/j.cb.20140206.12},
  url = {https://doi.org/10.11648/j.cb.20140206.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cb.20140206.12},
  abstract = {All types of cells of eukaryotic organisms produce and release small Nano-vesicles into their extracellular environment. Early studies have described these vesicles as “garbage bags” only to remove obsolete cellular molecules. Valadi and coworkers, in 2007, was the first who discovered the capability of circulating EVs to horizontally transfer functioning gene information between cells. These extra cellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemo-resistance, genetic exchange and signaling pathway activation through growth factor/receptor transfer. Extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived extracellular vesicles not only to represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we’ll be addressing the characteristics of different types and the clinical relevance of these extracellular EVs and their potentials as diagnostic markers as well as defining therapeutic options.},
 year = {2014}
}

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TY  - JOUR
T1  - Extracellular Vesicles (EVs); Basic Science, Clinical Relevance and Applications
AU  - Wael Nassar
AU  - Mervat El-Ansary
AU  - Mostafa Abdel Aziz
Y1  - 2014/12/22
PY  - 2014
N1  - https://doi.org/10.11648/j.cb.20140206.12
DO  - 10.11648/j.cb.20140206.12
T2  - Cell Biology
JF  - Cell Biology
JO  - Cell Biology
SP  - 60
EP  - 71
PB  - Science Publishing Group
SN  - 2330-0183
UR  - https://doi.org/10.11648/j.cb.20140206.12
AB  - All types of cells of eukaryotic organisms produce and release small Nano-vesicles into their extracellular environment. Early studies have described these vesicles as “garbage bags” only to remove obsolete cellular molecules. Valadi and coworkers, in 2007, was the first who discovered the capability of circulating EVs to horizontally transfer functioning gene information between cells. These extra cellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemo-resistance, genetic exchange and signaling pathway activation through growth factor/receptor transfer. Extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived extracellular vesicles not only to represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we’ll be addressing the characteristics of different types and the clinical relevance of these extracellular EVs and their potentials as diagnostic markers as well as defining therapeutic options.
VL  - 2
IS  - 6
ER  -

Copy | Download