Extracellular vesicles are involved in cell鈥搕o鈥揷ell communication and they transfer nucleic acids, proteins and lipids that can alter the phenotype of the recipient cell Circulating microvesicles and exosomes may contribute to the development of renal diseases by immunomodulation, thrombogenesis and matrix modulation Extracellular vesicles may have a therapeutic role in tissue regeneration after acute kidney injury Extracellular vesicles have the potential to transfer endogenous and exogenous therapeutic substances to recipient cells AbstractExtracellular vesicles, such as exosomes and microvesicles, are host cell-derived packages of information that allow cell鈥揷ell communication and enable cells to rid themselves of unwanted substances. The release and uptake of extracellular vesicles has important physiological functions and may also contribute to the development and propagation of inflammatory, vascular, malignant, infectious and neurodegenerative diseases. This Review describes the different types of extracellular vesicles, how they are detected and the mechanisms by which they communicate with cells and transfer information. We also describe their physiological functions in cellular interactions, such as in thrombosis, immune modulation, cell proliferation, tissue regeneration and matrix modulation, with an emphasis on renal processes. We discuss how the detection of extracellular vesicles could be utilized as bioMarkers of renal disease and how they might contribute to disease processes in the kidney, such as in acute kidney injury, chronic kidney disease, renal transplantation, thrombotic microangiopathies, vasculitides, IgA nephropathy, nephrotic syndrome, urinary tract infection, cystic kidney disease and tubulopathies. Finally, we consider how the release or uptake of extracellular vesicles can be blocked, as well as the associated benefits and risks, and how extracellular vesicles might be used to treat renal diseases by delivering therapeutics to specific cells. Subscription info for Chinese customersWe have a dedicated website for our Chinese customers. Please go to naturechina.com to subscribe to this journal.Go to naturechina.comRent or Buy articleGet time limited or full article access on ReadCube.from$8.99Rent or BuyAll prices are NET prices. Change history28 July 2017This article has been updated to remove some characters that were accidently inserted at the end of a word. The error did not impact on the scientific meaning. References1Colombo, M., Raposo, G. Thery, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 30, 255鈥?89 (2014).CAS聽 PubMed聽 Article聽Google Scholar聽 2Morel, O., Jesel, L., Freyssinet, J. M. Toti, F. Cellular mechanisms underlying the formation of circulating microparticles. Arterioscler. Thromb. Vasc. Biol. 31, 15鈥?6 (2011).CAS聽 Article聽 PubMed聽Google Scholar聽 3St氓hl, A. L., Sartz, L. Karpman, D. Complement activation on platelet鈥搇eukocyte complexes and microparticles in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome. Blood 117, 5503鈥?513 (2011). The paper presents complement-coated microvesicles in the circulation during HUS, suggesting a role in inflammation and thrombogenesis.Article聽 CAS聽 PubMed聽Google Scholar聽 4Iida, K., Whitlow, M. B. Nussenzweig, V. Membrane vesiculation protects erythrocytes from destruction by complement. J. Immunol. 147, 2638鈥?642 (1991).CAS聽 PubMed聽Google Scholar聽 5Mause, S. F. Weber, C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ. Res. 107, 1047鈥?057 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 6Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654鈥?59 (2007). Seminal paper demonstrating the capability of exosomes to transfer genetic material, even between species.CAS聽 Article聽 PubMed聽Google Scholar聽 7Ratajczak, J., Wysoczynski, M., Hayek, F., Janowska-Wieczorek, A. Ratajczak, M. Z. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 20, 1487鈥?495 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 8Deregibus, M. C. et al. Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 110, 2440鈥?448 (2007).CAS聽 Article聽 PubMed聽Google Scholar聽 9Davizon, P., Munday, A. D. Lopez, J. A. Tissue factor, lipid rafts, and microparticles. Semin. Thromb. Hemost. 36, 857鈥?64 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 10Del Conde, I., Shrimpton, C. N., Thiagarajan, P. Lopez, J. A. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106, 1604鈥?611 (2005). Describes the importance of tissue factor and lipid rafts on microvesicles.CAS聽 Article聽 PubMed聽Google Scholar聽 11Sinauridze, E. I. et al. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb. Haemost. 97, 425鈥?34 (2007).CAS聽 Article聽 PubMed聽Google Scholar聽 12Pluskota, E. et al. Expression, activation, and function of integrin alphaMbeta2 (Mac-1) on neutrophil-derived microparticles. Blood 112, 2327鈥?335 (2008).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 13Meckes, D. G. Jr Raab-Traub, N. Microvesicles and viral infection. J. Virol. 85, 12844鈥?2854 (2011).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 14St氓hl, A. L. et al. A novel mechanism of bacterial toxin transfer within host blood cell-derived microvesicles. PLoS Pathog. 11, e1004619 (2015). This paper describes a novel mechanism of bacterial virulence whereby host-derived blood cell microvesicles transfer a bacterial virulence factor to the kidneys.Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 15Keller, S. et al. CD24 is a marker of exosomes secreted into urine and amniotic fluid. Kidney Int. 72, 1095鈥?102 (2007).CAS聽 Article聽 PubMed聽Google Scholar聽 16Nilsson, J. et al. Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br. J. Cancer 100, 1603鈥?607 (2009).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 17Stegmayr, B. Ronquist, G. Promotive effect on human sperm progressive motility by prostasomes. Urol. Res. 10, 253鈥?57 (1982).CAS聽 Article聽 PubMed聽Google Scholar聽 18Street, J. M. et al. Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J. Transl Med. 10, 5 (2012).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 19Gyorgy, B. et al. Improved flow cytometric assessment reveals distinct microvesicle (cell-derived microparticle) signatures in joint diseases. PLoS ONE 7, e49726 (2012).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 20Admyre, C. et al. Exosomes with immune modulatory features are present in human breast milk. J. Immunol. 179, 1969鈥?978 (2007).CAS聽 Article聽 PubMed聽Google Scholar聽 21Michael, A. et al. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis. 16, 34鈥?8 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 22Severino, V. et al. Extracellular vesicles in bile as markers of malignant biliary stenoses. Gastroenterology http://dx.doi.org/10.1053/j.gastro.2017.04.043 (2017).23Andre, F. et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet 360, 295鈥?05 (2002).CAS聽 Article聽 PubMed聽Google Scholar聽 24van Balkom, B. W., Pisitkun, T., Verhaar, M. C. Knepper, M. A. Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases. Kidney Int. 80, 1138鈥?145 (2011). An excellent review of exosomes in renal diseases.CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 25Skokos, D. et al. Mast cell-dependent B and T lymphocyte activation is mediated by the secretion of immunologically active exosomes. J. Immunol. 166, 868鈥?76 (2001).CAS聽 Article聽 PubMed聽Google Scholar聽 26Combes, V. et al. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J. Clin. Invest. 104, 93鈥?02 (1999).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 27Sapet, C. et al. Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2. Blood 108, 1868鈥?876 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 28Faure, V. et al. Elevation of circulating endothelial microparticles in patients with chronic renal failure. J. Thromb. Haemost. 4, 566鈥?73 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 29Cocucci, E., Racchetti, G. Meldolesi, J. Shedding microvesicles: artefacts no more. Trends Cell Biol. 19, 43鈥?1 (2009).CAS聽 Article聽 PubMed聽Google Scholar聽 30Bianco, F. et al. Astrocyte-derived ATP induces vesicle shedding and IL-1 beta release from microglia. J. Immunol. 174, 7268鈥?277 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 31Pizzirani, C. et al. Stimulation of P2 receptors causes release of IL-1beta-loaded microvesicles from human dendritic cells. Blood 109, 3856鈥?864 (2007).CAS聽 Article聽 PubMed聽Google Scholar聽 32Tati, R. et al. Complement activation associated with ADAMTS13 deficiency in human and murine thrombotic microangiopathy. J. Immunol. 191, 2184鈥?193 (2013). This paper describes the release of complement-coated endothelial-derived microvesicles when plasma from patients with TTP is perfused over glomerular endothelial cells.CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 33Park, J. E. et al. Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol. Cell. Proteomics 9, 1085鈥?099 (2010).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 34Lehmann, B. D. et al. Senescence-associated exosome release from human prostate cancer cells. Cancer Res. 68, 7864鈥?871 (2008).CAS聽 Article聽 PubMed聽Google Scholar聽 35El Andaloussi, S., Mager, I., Breakefield, X. O. Wood, M. J. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov. 12, 347鈥?57 (2013). An excellent review covering the potential of extracellular vesicles in therapeutics.CAS聽 Article聽 PubMed聽Google Scholar聽 36Adell, M. A. et al. Coordinated binding of Vps4 to ESCRT-III drives membrane neck constriction during MVB vesicle formation. J. Cell Biol. 205, 33鈥?9 (2014).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 37Guescini, M., Genedani, S., Stocchi, V. Agnati, L. F. Astrocytes and glioblastoma cells release exosomes carrying mtDNA. J. Neural Transm. (Vienna) 117, 1鈥? (2010).CAS聽 Article聽Google Scholar聽 38Colombo, M. et al. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J. Cell Sci. 126, 5553鈥?565 (2013).CAS聽 Article聽 PubMed聽Google Scholar聽 39Crescitelli, R. et al. Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes. J. Extracell. Vesicles 2, 20677 (2013).Article聽 CAS聽Google Scholar聽 40Boulanger, C. M., Amabile, N. Tedgui, A. Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. Hypertension 48, 180鈥?86 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 41Chironi, G. N. et al. Endothelial microparticles in diseases. Cell Tissue Res. 335, 143鈥?51 (2009).Article聽 PubMed聽Google Scholar聽 42Muralidharan-Chari, V. et al. ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr. Biol. 19, 1875鈥?885 (2009).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 43Daleke, D. L. Regulation of transbilayer plasma membrane phospholipid asymmetry. J. Lipid Res. 44, 233鈥?42 (2003).CAS聽 Article聽 PubMed聽Google Scholar聽 44Bevers, E. M. Williamson, P. L. Phospholipid scramblase: an update. FEBS Lett. 584, 2724鈥?730 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 45Suzuki, J., Umeda, M., Sims, P. J. Nagata, S. Calcium-dependent phospholipid scrambling by TMEM16F. Nature 468, 834鈥?38 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 46Yang, H. et al. TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation. Cell 151, 111鈥?22 (2012).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 47Fujii, T., Sakata, A., Nishimura, S., Eto, K. Nagata, S. TMEM16F is required for phosphatidylserine exposure and microparticle release in activated mouse platelets. Proc. Natl Acad. Sci. USA 112, 12800鈥?2805 (2015).CAS聽 Article聽 PubMed聽Google Scholar聽 48Kim, D. K. et al. EVpedia: a community web portal for extracellular vesicles research. Bioinformatics 31, 933鈥?39 (2015).CAS聽 Article聽 PubMed聽Google Scholar聽 49Lai, R. C. et al. MSC secretes at least 3 EV types each with a unique permutation of membrane lipid, protein and RNA. J. Extracell. Vesicles 5, 29828 (2016).Article聽 CAS聽 PubMed聽Google Scholar聽 50Jimenez, J. J. et al. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. Thromb. Res. 109, 175鈥?80 (2003).CAS聽 Article聽 PubMed聽Google Scholar聽 51de Gassart, A., Geminard, C., Fevrier, B., Raposo, G. Vidal, M. Lipid raft-associated protein sorting in exosomes. Blood 102, 4336鈥?344 (2003).CAS聽 Article聽 PubMed聽Google Scholar聽 52Biro, E. et al. The phospholipid composition and cholesterol content of platelet-derived microparticles: a comparison with platelet membrane fractions. J. Thromb. Haemost. 3, 2754鈥?763 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 53Yanez-Mo, M. et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 4, 27066 (2015).Article聽 PubMed聽Google Scholar聽 54Mulcahy, L. A., Pink, R. C. Carter, D. R. Routes and mechanisms of extracellular vesicle uptake. J. Extracell. Vesicles 3, 24641 (2014).Article聽 CAS聽Google Scholar聽 55George, J. N., Thoi, L. L., McManus, L. M. Reimann, T. A. Isolation of human platelet membrane microparticles from plasma and serum. Blood 60, 834鈥?40 (1982).CAS聽 PubMed聽Google Scholar聽 56Arvidsson, I. et al. Shiga toxin-induced complement-mediated hemolysis and release of complement-coated red blood cell-derived microvesicles in hemolytic uremic syndrome. J. Immunol. 194, 2309鈥?318 (2015). The paper describes the involvement of red blood cell-derived microvesicles in haemolysis and inhibition by purinergic receptor inhibitors.CAS聽 Article聽 PubMed聽Google Scholar聽 57Mossberg, M. et al. C1-inhibitor decreases the release of vasculitis-like chemotactic endothelial microvesicles. J. Am. Soc. Nephrol. http://dx.doi.org/10.1681/ASN.2016060637 (2017). This paper describes the chemotactic potential of endothelial-derived microvesicles positive for both kinin receptors, B1 and B2, and IL-8, and inhibition of their release by C1 inhibitor.58Fang, D. Y., King, H. W., Li, J. Y. Gleadle, J. M. Exosomes and the kidney: blaming the messenger. Nephrology (Carlton) 18, 1鈥?0 (2013).CAS聽 Article聽Google Scholar聽 59Zhou, H. et al. Urinary exosomal transcription factors, a new class of biomarkers for renal disease. Kidney Int. 74, 613鈥?21 (2008).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 60Dear, J. W., Street, J. M. Bailey, M. A. Urinary exosomes: a reservoir for biomarker discovery and potential mediators of intrarenal signalling. Proteomics 13, 1572鈥?580 (2013).CAS聽 Article聽 PubMed聽Google Scholar聽 61Pisitkun, T., Shen, R. F. Knepper, M. A. Identification and proteomic profiling of exosomes in human urine. Proc. Natl Acad. Sci. USA 101, 13368鈥?3373 (2004). A comprehensive study of exosomes in urine.CAS聽 Article聽 PubMed聽Google Scholar聽 62Erdbrugger, U. Le, T. H. Extracellular vesicles in renal diseases: more than novel biomarkers? J. Am. Soc. Nephrol. 27, 12鈥?6 (2016).CAS聽 Article聽 PubMed聽Google Scholar聽 63van der Pol, E. et al. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J. Thromb. Haemost. 12, 1182鈥?192 (2014).CAS聽 Article聽 PubMed聽Google Scholar聽 64Erdbrugger, U. Lannigan, J. Analytical challenges of extracellular vesicle detection: a comparison of different techniques. Cytometry A 89, 123鈥?34 (2016). A review describing and comparing methods for detection of extracellular vesicles.Article聽 CAS聽 PubMed聽Google Scholar聽 65Maas, S. L. et al. Possibilities and limitations of current technologies for quantification of biological extracellular vesicles and synthetic mimics. J. Control. Release 200, 87鈥?6 (2015).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 66Oosthuyzen, W. et al. Quantification of human urinary exosomes by nanoparticle tracking analysis. J. Physiol. 591, 5833鈥?842 (2013).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 67Murakami, T. et al. Development of glomerulus-, tubule-, and collecting duct-specific mRNA assay in human urinary exosomes and microvesicles. PLoS ONE 9, e109074 (2014).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 68Rood, I. M. et al. Comparison of three methods for isolation of urinary microvesicles to identify biomarkers of nephrotic syndrome. Kidney Int. 78, 810鈥?16 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 69Salih, M., Zietse, R. Hoorn, E. J. Urinary extracellular vesicles and the kidney: biomarkers and beyond. Am. J. Physiol. Renal Physiol. 306, F1251鈥揊1259 (2014).CAS聽 Article聽 PubMed聽Google Scholar聽 70Wang, D. Sun, W. Urinary extracellular microvesicles: isolation methods and prospects for urinary proteome. Proteomics 14, 1922鈥?932 (2014).CAS聽 Article聽 PubMed聽Google Scholar聽 71Tricarico, C., Clancy, J. D\'Souza-Schorey, C. Biology and biogenesis of shed microvesicles. Small GTPases http://dx.doi.org/10.1080/21541248.2016.1215283 (2016).72Clancy, J. W., Tricarico, C. J. D\'Souza-Schorey, C. Tumor-derived microvesicles in the tumor microenvironment: how vesicle heterogeneity can shape the future of a rapidly expanding field. Bioessays 37, 1309鈥?316 (2015).CAS聽 Article聽 PubMed聽Google Scholar聽 73Laulagnier, K. et al. Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem. J. 380, 161鈥?71 (2004).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 74Bolukbasi, M. F. et al. miR-1289 and 鈥渮ipcode鈥?like sequence enrich mRNAs in microvesicles. Mol. Ther. Nucleic Acids 1, e10 (2012).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 75Alexy, T., Rooney, K., Weber, M., Gray, W. D. Searles, C. D. TNF-alpha alters the release and transfer of microparticle-encapsulated miRNAs from endothelial cells. Physiol. Genomics 46, 833鈥?40 (2014).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 76Parolini, I. et al. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J. Biol. Chem. 284, 34211鈥?4222 (2009).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 77Nolte-\'t Hoen, E. N., Buschow, S. I., Anderton, S. M., Stoorvogel, W. Wauben, M. H. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood 113, 1977鈥?981 (2009).CAS聽 Article聽 PubMed聽Google Scholar聽 78Dasgupta, S. K., Le, A., Chavakis, T., Rumbaut, R. E. Thiagarajan, P. Developmental endothelial locus-1 (Del-1) mediates clearance of platelet microparticles by the endothelium. Circulation 125, 1664鈥?672 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 79Collino, F. et al. AKI recovery induced by mesenchymal stromal cell-derived extracellular vesicles carrying microRNAs. J. Am. Soc. Nephrol. 26, 2349鈥?360 (2015).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 80Quesenberry, P. J. et al. Cellular phenotype and extracellular vesicles: basic and clinical considerations. Stem Cells Dev. 23, 1429鈥?436 (2014).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 81Pegtel, D. M. et al. Functional delivery of viral miRNAs via exosomes. Proc. Natl Acad. Sci. USA 107, 6328鈥?333 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 82Balaj, L. et al. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat. Commun. 2, 180 (2011).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 83Thakur, B. K. et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res. 24, 766鈥?69 (2014).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 84Kahlert, C. et al. Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J. Biol. Chem. 289, 3869鈥?875 (2014).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 85Miranda, K. C. et al. Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease. Kidney Int. 78, 191鈥?99 (2010).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 86Muhsin-Sharafaldine, M. R. et al. Procoagulant and immunogenic properties of melanoma exosomes, microvesicles and apoptotic vesicles. Oncotarget 7, 56279鈥?6294 (2016).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 87Spees, J. L., Olson, S. D., Whitney, M. J. Prockop, D. J. Mitochondrial transfer between cells can rescue aerobic respiration. Proc. Natl Acad. Sci. USA 103, 1283鈥?288 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 88Phinney, D. G. et al. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat. Commun. 6, 8472 (2015).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 89Hayakawa, K. et al. Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535, 551鈥?55 (2016).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 90Mack, M. et al. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nat. Med. 6, 769鈥?75 (2000). The first description of microvesicles transferring functional receptors involved in inflammatory signalling.CAS聽 Article聽 PubMed聽Google Scholar聽 91Al-Nedawi, K., Meehan, B., Kerbel, R. S., Allison, A. C. Rak, J. Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc. Natl Acad. Sci. USA 106, 3794鈥?799 (2009).Article聽 PubMed聽Google Scholar聽 92Rozmyslowicz, T. et al. Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV. AIDS 17, 33鈥?2 (2003). This paper describes microvesicle transfer of functional receptors involved in inflammatory signalling.CAS聽 Article聽 PubMed聽Google Scholar聽 93Baj-Krzyworzeka, M. et al. Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells. Exp. Hematol. 30, 450鈥?59 (2002).CAS聽 Article聽 PubMed聽Google Scholar聽 94Salanova, B. et al. Beta2-integrins and acquired glycoprotein IIb/IIIa (GPIIb/IIIa) receptors cooperate in NF-kappaB activation of human neutrophils. J. Biol. Chem. 282, 27960鈥?7969 (2007).CAS聽 Article聽 PubMed聽Google Scholar聽 95Kahn, R. et al. Microvesicle transfer of kinin B1-receptors is a novel inflammatory mechanism in vasculitis. Kidney Int. 91, 96鈥?05 (2017). This paper describes transfer of functional kinin receptors between cells by microvesicles.CAS聽 Article聽 PubMed聽Google Scholar聽 96Janowska-Wieczorek, A. et al. Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood 98, 3143鈥?149 (2001).CAS聽 Article聽 PubMed聽Google Scholar聽 97Barry, O. P., Pratico, D., Lawson, J. A. FitzGerald, G. A. Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. J. Clin. Invest. 99, 2118鈥?127 (1997).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 98Giri, P. K. Schorey, J. S. Exosomes derived from M. Bovis BCG infected macrophages activate antigen-specific CD4+ and CD8+ T cells in vitro and in vivo. PLoS ONE 3, e2461 (2008).PubMed聽 PubMed Central聽 Article聽Google Scholar聽 99Walker, J. D., Maier, C. L. Pober, J. S. Cytomegalovirus-infected human endothelial cells can stimulate allogeneic CD4+ memory T cells by releasing antigenic exosomes. J. Immunol. 182, 1548鈥?559 (2009).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 100Gould, S. J., Booth, A. M. Hildreth, J. E. The Trojan exosome hypothesis. Proc. Natl Acad. Sci. USA 100, 10592鈥?0597 (2003).CAS聽 Article聽 PubMed聽Google Scholar聽 101Chaput, N. Thery, C. Exosomes: immune properties and potential clinical implementations. Semin. Immunopathol. 33, 419鈥?40 (2011).CAS聽 Article聽 PubMed聽Google Scholar聽 102Mesri, M. Altieri, D. C. Endothelial cell activation by leukocyte microparticles. J. Immunol. 161, 4382鈥?387 (1998).CAS聽 PubMed聽Google Scholar聽 103Gasser, O. Schifferli, J. A. Activated polymorphonuclear neutrophils disseminate anti-inflammatory microparticles by ectocytosis. Blood 104, 2543鈥?548 (2004).CAS聽 Article聽 PubMed聽Google Scholar聽 104Distler, J. H., Huber, L. C., Gay, S., Distler, O. Pisetsky, D. S. Microparticles as mediators of cellular cross-talk in inflammatory disease. Autoimmunity 39, 683鈥?90 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 105Burrello, J. et al. Stem cell-derived extracellular vesicles and immune-modulation. Front. Cell Dev. Biol. 4, 83 (2016).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 106Peche, H., Heslan, M., Usal, C., Amigorena, S. Cuturi, M. C. Presentation of donor major histocompatibility complex antigens by bone marrow dendritic cell-derived exosomes modulates allograft rejection. Transplantation 76, 1503鈥?510 (2003).CAS聽 Article聽 PubMed聽Google Scholar聽 107Miksa, M. et al. Dendritic cell-derived exosomes containing milk fat globule epidermal growth factor-factor VIII attenuate proinflammatory responses in sepsis. Shock 25, 586鈥?93 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 108Sadallah, S., Eken, C., Martin, P. J. Schifferli, J. A. Microparticles (ectosomes) shed by stored human platelets downregulate macrophages and modify the development of dendritic cells. J. Immunol. 186, 6543鈥?552 (2011).CAS聽 Article聽 PubMed聽Google Scholar聽 109Sprague, D. L. et al. Platelet-mediated modulation of adaptive immunity: unique delivery of CD154 signal by platelet-derived membrane vesicles. Blood 111, 5028鈥?036 (2008).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 110Brown, G. T. McIntyre, T. M. Lipopolysaccharide signaling without a nucleus: kinase cascades stimulate platelet shedding of proinflammatory IL-1beta-rich microparticles. J. Immunol. 186, 5489鈥?496 (2011).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 111Barry, O. P., Pratico, D., Savani, R. C. FitzGerald, G. A. Modulation of monocyte-endothelial cell interactions by platelet microparticles. J. Clin. Invest. 102, 136鈥?44 (1998).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 112Mause, S. F., von Hundelshausen, P., Zernecke, A., Koenen, R. R. Weber, C. Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler. Thromb. Vasc. Biol. 25, 1512鈥?518 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 113Sims, P. J., Faioni, E. M., Wiedmer, T. Shattil, S. J. Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity. J. Biol. Chem. 263, 18205鈥?8212 (1988).CAS聽 PubMed聽Google Scholar聽 114St氓hl, A. L. et al. Factor H dysfunction in patients with atypical hemolytic uremic syndrome contributes to complement deposition on platelets and their activation. Blood 111, 5307鈥?315 (2008). This paper describes complement-coated platelets releasing tissue factor-positive microvesicles and inhibition by addition of factor H to prevent complement activation on blood cells in atypical HUS.Article聽 CAS聽 PubMed聽Google Scholar聽 115Yin, W., Ghebrehiwet, B. Peerschke, E. I. Expression of complement components and inhibitors on platelet microparticles. Platelets 19, 225鈥?33 (2008).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 116Rabesandratana, H., Toutant, J. P., Reggio, H. Vidal, M. Decay-accelerating factor (CD55) and membrane inhibitor of reactive lysis (CD59) are released within exosomes during in vitro maturation of reticulocytes. Blood 91, 2573鈥?580 (1998).CAS聽 PubMed聽Google Scholar聽 117Bevers, E. M. Williamson, P. L. Getting to the outer leaflet: physiology of phosphatidylserine exposure at the plasma membrane. Physiol. Rev. 96, 605鈥?45 (2016).CAS聽 Article聽 PubMed聽Google Scholar聽 118Falati, S. et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J. Exp. Med. 197, 1585鈥?598 (2003).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 119St氓hl, A. L., Sartz, L., Nelsson, A., B茅k谩ssy, Z. D. Karpman, D. Shiga toxin and lipopolysaccharide induce platelet-leukocyte aggregates and tissue factor release, a thrombotic mechanism in hemolytic uremic syndrome. PLoS ONE 4, e6990 (2009). The presence of tissue factor on blood cell-derived microvesicles could contribute to thrombotic microangiopathy.Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 120Abid Hussein, M. N. et al. Phospholipid composition of in vitro endothelial microparticles and their in vivo thrombogenic properties. Thromb. Res. 121, 865鈥?71 (2008).CAS聽 Article聽 PubMed聽Google Scholar聽 121Sabatier, F. et al. Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. Blood 99, 3962鈥?970 (2002).CAS聽 Article聽 PubMed聽Google Scholar聽 122Raturi, A., Miersch, S., Hudson, J. W. Mutus, B. Platelet microparticle-associated protein disulfide isomerase promotes platelet aggregation and inactivates insulin. Biochim. Biophys. Acta 1778, 2790鈥?796 (2008).CAS聽 Article聽 PubMed聽Google Scholar聽 123Gilbert, G. E. et al. Platelet-derived microparticles express high affinity receptors for factor VIII. J. Biol. Chem. 266, 17261鈥?7268 (1991).CAS聽 PubMed聽Google Scholar聽 124Van Der Meijden, P. E. et al. Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa. J. Thromb. Haemost. 10, 1355鈥?362 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 125Connor, D. E., Exner, T., Ma, D. D. Joseph, J. E. The majority of circulating platelet-derived microparticles fail to bind annexin V, lack phospholipid-dependent procoagulant activity and demonstrate greater expression of glycoprotein Ib. Thromb. Haemost. 103, 1044鈥?052 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 126Rossaint, J. et al. Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response. Nat. Commun. 7, 13464 (2016).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 127Berckmans, R. J. et al. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb. Haemost. 85, 639鈥?46 (2001).CAS聽 Article聽 PubMed聽Google Scholar聽 128Tans, G. et al. Comparison of anticoagulant and procoagulant activities of stimulated platelets and platelet-derived microparticles. Blood 77, 2641鈥?648 (1991).CAS聽 PubMed聽Google Scholar聽 129Abid Hussein, M. N., Boing, A. N., Sturk, A., Hau, C. M. Nieuwland, R. Inhibition of microparticle release triggers endothelial cell apoptosis and detachment. Thromb. Haemost. 98, 1096鈥?107 (2007).Article聽 CAS聽 PubMed聽Google Scholar聽 130Perez-Casal, M., Downey, C., Fukudome, K., Marx, G. Toh, C. H. Activated protein C induces the release of microparticle-associated endothelial protein C receptor. Blood 105, 1515鈥?522 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 131Perez-Casal, M. et al. Microparticle-associated endothelial protein C receptor and the induction of cytoprotective and anti-inflammatory effects. Haematologica 94, 387鈥?94 (2009).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 132Janowska-Wieczorek, A. et al. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int. J. Cancer 113, 752鈥?60 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 133Hood, J. L. et al. Paracrine induction of endothelium by tumor exosomes. Lab. Invest. 89, 1317鈥?328 (2009).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 134Mezentsev, A. et al. Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress. Am. J. Physiol. Heart Circ. Physiol. 289, H1106鈥揌1114 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 135Kim, H. K., Song, K. S., Chung, J. H., Lee, K. R. Lee, S. N. Platelet microparticles induce angiogenesis in vitro. Br. J. Haematol. 124, 376鈥?84 (2004).Article聽 PubMed聽Google Scholar聽 136Chen, J. et al. Proangiogenic compositions of microvesicles derived from human umbilical cord mesenchymal stem cells. PLoS ONE 9, e115316 (2014).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 137Brill, A., Dashevsky, O., Rivo, J., Gozal, Y. Varon, D. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc. Res. 67, 30鈥?8 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 138Riazifar, M., Pone, E. J., Lotvall, J. Zhao, W. Stem cell extracellular vesicles: extended messages of regeneration. Annu. Rev. Pharmacol. Toxicol. 57, 125鈥?54 (2017).CAS聽 Article聽 PubMed聽Google Scholar聽 139Aliotta, J. M. et al. Alteration of marrow cell gene expression, protein production, and engraftment into lung by lung-derived microvesicles: a novel mechanism for phenotype modulation. Stem Cells 25, 2245鈥?256 (2007).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 140Sedgwick, A. E., Clancy, J. W., Olivia Balmert, M. D\'Souza-Schorey, C. Extracellular microvesicles and invadopodia mediate non-overlapping modes of tumor cell invasion. Sci. Rep. 5, 14748 (2015).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 141Graves, L. E. et al. Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Res. 64, 7045鈥?049 (2004).CAS聽 Article聽 PubMed聽Google Scholar聽 142Clancy, J. W. et al. Regulated delivery of molecular cargo to invasive tumour-derived microvesicles. Nat. Commun. 6, 6919 (2015).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 143McCready, J., Sims, J. D., Chan, D. Jay, D. G. Secretion of extracellular hsp90alpha via exosomes increases cancer cell motility: a role for plasminogen activation. BMC Cancer 10, 294 (2010).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 144Bruno, S. et al. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J. Am. Soc. Nephrol. 20, 1053鈥?067 (2009).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 145Oosthuyzen, W. et al. Vasopressin regulates extracellular vesicle uptake by kidney collecting duct cells. J. Am. Soc. Nephrol. 27, 3345鈥?355 (2016).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 146Cheng, Y. et al. A translational study of urine miRNAs in acute myocardial infarction. J. Mol. Cell. Cardiol. 53, 668鈥?76 (2012).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 147Gonzales, P. A. et al. Large-scale proteomics and phosphoproteomics of urinary exosomes. J. Am. Soc. Nephrol. 20, 363鈥?79 (2009).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 148Street, J. M. et al. Exosomal transmission of functional aquaporin 2 in kidney cortical collecting duct cells. J. Physiol. 589, 6119鈥?127 (2011).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 149Winyard, P. J. Price, K. L. Experimental renal progenitor cells: repairing and recreating kidneys? Pediatr. Nephrol. 29, 665鈥?72 (2014).Article聽 PubMed聽Google Scholar聽 150Ranghino, A. et al. The effects of glomerular and tubular renal progenitors and derived extracellular vesicles on recovery from acute kidney injury. Stem Cell Res. Ther. 8, 24 (2017).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 151Turco, A. E. et al. Specific renal parenchymal-derived urinary extracellular vesicles identify age-associated structural changes in living donor kidneys. J. Extracell. Vesicles 5, 29642 (2016).Article聽 CAS聽 PubMed聽Google Scholar聽 152Karpman, D., Loos, S., Tati, R. Arvidsson, I. Haemolytic uraemic syndrome. J. Intern. Med. 281, 123鈥?48 (2017).Article聽 PubMed聽Google Scholar聽 153Ge, S. et al. Microparticle generation and leucocyte death in Shiga toxin-mediated HUS. Nephrol. Dial. Transplant. 27, 2768鈥?775 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 154Brigotti, M. et al. Clinical relevance of shiga toxin concentrations in the blood of patients with hemolytic uremic syndrome. Pediatr. Infect. Dis. J. 30, 486鈥?90 (2011).Article聽 PubMed聽Google Scholar聽 155Karpman, D. et al. Platelet activation by Shiga toxin and circulatory factors as a pathogenetic mechanism in the hemolytic uremic syndrome. Blood 97, 3100鈥?108 (2001).CAS聽 Article聽 PubMed聽Google Scholar聽 156Zoja, C., Buelli, S. Morigi, M. Shiga toxin-associated hemolytic uremic syndrome: pathophysiology of endothelial dysfunction. Pediatr. Nephrol. 25, 2231鈥?240 (2010).Article聽 PubMed聽Google Scholar聽 157Afshar-Kharghan, V. Unleashed platelets in aHUS. Blood 111, 5266 (2008).CAS聽 Article聽 PubMed聽Google Scholar聽 158Levy, G. G. et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 413, 488鈥?94 (2001).CAS聽 Article聽 PubMed聽Google Scholar聽 159Manea, M. Karpman, D. Molecular basis of ADAMTS13 dysfunction in thrombotic thrombocytopenic purpura. Pediatr. Nephrol. 24, 447鈥?58 (2009).Article聽 PubMed聽Google Scholar聽 160Tsai, H. M. Pathophysiology of thrombotic thrombocytopenic purpura. Int. J. Hematol. 91, 1鈥?9 (2010).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 161Kelton, J. G., Warkentin, T. E., Hayward, C. P., Murphy, W. G. Moore, J. C. Calpain activity in patients with thrombotic thrombocytopenic purpura is associated with platelet microparticles. Blood 80, 2246鈥?251 (1992).CAS聽 PubMed聽Google Scholar聽 162Jimenez, J. J. et al. Endothelial microparticles released in thrombotic thrombocytopenic purpura express von Willebrand factor and markers of endothelial activation. Br. J. Haematol. 123, 896鈥?02 (2003).Article聽 PubMed聽Google Scholar聽 163Brogan, P. A. et al. Endothelial and platelet microparticles in vasculitis of the young. Arthritis Rheum. 50, 927鈥?36 (2004).CAS聽 Article聽 PubMed聽Google Scholar聽 164Erdbruegger, U. et al. Diagnostic role of endothelial microparticles in vasculitis. Rheumatology (Oxford) 47, 1820鈥?825 (2008).CAS聽 Article聽Google Scholar聽 165Clarke, L. A. et al. Endothelial injury and repair in systemic vasculitis of the young. Arthritis Rheum. 62, 1770鈥?780 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 166Daniel, L. et al. Increase of circulating neutrophil and platelet microparticles during acute vasculitis and hemodialysis. Kidney Int. 69, 1416鈥?423 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 167Hong, Y. et al. Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles. J. Am. Soc. Nephrol. 23, 49鈥?2 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 168Gasser, O. et al. Characterisation and properties of ectosomes released by human polymorphonuclear neutrophils. Exp. Cell Res. 285, 243鈥?57 (2003).CAS聽 Article聽 PubMed聽Google Scholar聽 169Hogan, M. C. et al. Subfractionation, characterization, and in-depth proteomic analysis of glomerular membrane vesicles in human urine. Kidney Int. 85, 1225鈥?237 (2014).CAS聽 Article聽 PubMed聽Google Scholar聽 170Huang, Y. M., Wang, H., Wang, C., Chen, M. Zhao, M. H. Promotion of hypercoagulability in antineutrophil cytoplasmic antibody-associated vasculitis by C5a-induced tissue factor-expressing microparticles and neutrophil extracellular traps. Arthritis Rheumatol. 67, 2780鈥?790 (2015).Article聽 PubMed聽Google Scholar聽 171Eleftheriou, D., Hong, Y., Klein, N. J. Brogan, P. A. Thromboembolic disease in systemic vasculitis is associated with enhanced microparticle-mediated thrombin generation. J. Thromb. Haemost. 9, 1864鈥?867 (2011).CAS聽 Article聽 PubMed聽Google Scholar聽 172Kahn, R. et al. Contact-system activation in children with vasculitis. Lancet 360, 535鈥?41 (2002).Article聽 PubMed聽Google Scholar聽 173Kahn, R. et al. Neutrophil-derived proteinase 3 induces kallikrein-independent release of a novel vasoactive kinin. J. Immunol. 182, 7906鈥?915 (2009).CAS聽 Article聽 PubMed聽Google Scholar聽 174Mack, M. Leukocyte-derived microvesicles dock on glomerular endothelial cells: stardust in the kidney. Kidney Int. 91, 13鈥?5 (2017).CAS聽 Article聽 PubMed聽Google Scholar聽 175Duan, Z. Y. et al. Selection of urinary sediment miRNAs as specific biomarkers of IgA nephropathy. Sci. Rep. 6, 23498 (2016). A paper describing urinary erythrocyte miRNAs derived from microvesicles as biomarkers of IgA nephropathy.CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 176Wang, G. et al. Elevated levels of miR-146a and miR-155 in kidney biopsy and urine from patients with IgA nephropathy. Dis. Markers 30, 171鈥?79 (2011).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 177Moon, P. G. et al. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy. Proteomics 11, 2459鈥?475 (2011).CAS聽 Article聽 PubMed聽Google Scholar聽 178Zhou, H. et al. Urinary exosomal Wilms\' tumor-1 as a potential biomarker for podocyte injury. Am. J. Physiol. Renal Physiol. 305, F553鈥揊559 (2013).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 179Lee, H. et al. Urinary exosomal WT1 in childhood nephrotic syndrome. Pediatr. Nephrol. 27, 317鈥?20 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 180Rood, I. M. et al. Increased expression of lysosome membrane protein 2 in glomeruli of patients with idiopathic membranous nephropathy. Proteomics 15, 3722鈥?730 (2015).CAS聽 Article聽 PubMed聽Google Scholar聽 181Gao, C. et al. Procoagulant activity of erythrocytes and platelets through phosphatidylserine exposure and microparticles release in patients with nephrotic syndrome. Thromb. Haemost. 107, 681鈥?89 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 182Eyre, J. et al. Monocyte- and endothelial-derived microparticles induce an inflammatory phenotype in human podocytes. Nephron Exp. Nephrol. 119, e58鈥揺66 (2011).CAS聽 Article聽 PubMed聽Google Scholar聽 183Woei, A. J. F. J. et al. Procoagulant tissue factor activity on microparticles is associated with disease severity and bacteremia in febrile urinary tract infections. Thromb. Res. 133, 799鈥?03 (2014).Article聽 CAS聽Google Scholar聽 184Hiemstra, T. F. et al. Human urinary exosomes as innate immune effectors. J. Am. Soc. Nephrol. 25, 2017鈥?027 (2014).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 185Hogan, M. C. et al. Identification of biomarkers for PKD1 using urinary exosomes. J. Am. Soc. Nephrol. 26, 1661鈥?670 (2015).CAS聽 Article聽 PubMed聽Google Scholar聽 186Hogan, M. C. et al. Characterization of PKD protein-positive exosome-like vesicles. J. Am. Soc. Nephrol. 20, 278鈥?88 (2009).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 187Ben-Dov, I. Z. et al. Urine microRNA as potential biomarkers of autosomal dominant polycystic kidney disease progression: description of miRNA profiles at baseline. PLoS ONE 9, e86856 (2014).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 188Joo, K. W. et al. Reduced urinary excretion of thiazide-sensitive Na-Cl cotransporter in Gitelman syndrome: preliminary data. Am. J. Kidney Dis. 50, 765鈥?73 (2007).CAS聽 Article聽 PubMed聽Google Scholar聽 189Tokes-Fuzesi, M. et al. Microparticles and acute renal dysfunction in septic patients. J. Crit. Care 28, 141鈥?47 (2013).CAS聽 Article聽 PubMed聽Google Scholar聽 190Martino, F. et al. Circulating microRNAs are not eliminated by hemodialysis. PLoS ONE 7, e38269 (2012).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 191Cantaluppi, V. et al. Protective effect of resin adsorption on septic plasma-induced tubular injury. Crit. Care 14, R4 (2010).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 192Mariano, F. et al. Circulating plasma factors induce tubular and glomerular alterations in septic burns patients. Crit. Care 12, R42 (2008).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 193du Cheyron, D. et al. Urinary measurement of Na+/H+ exchanger isoform 3 (NHE3) protein as new marker of tubule injury in critically ill patients with ARF. Am. J. Kidney Dis. 42, 497鈥?06 (2003).CAS聽 Article聽 PubMed聽Google Scholar聽 194Zhou, H. et al. Exosomal Fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury. Kidney Int. 70, 1847鈥?857 (2006).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 195Chen, H. H. et al. Exosomal ATF3 RNA attenuates pro-inflammatory gene MCP-1 transcription in renal ischemia-reperfusion. J. Cell. Physiol. 229, 1202鈥?211 (2014).CAS聽 Article聽 PubMed聽Google Scholar聽 196Mostefai, H. A. et al. Circulating microparticles from patients with septic shock exert protective role in vascular function. Am. J. Respir. Crit. Care Med. 178, 1148鈥?155 (2008).CAS聽 Article聽 PubMed聽Google Scholar聽 197Delabranche, X. et al. Microparticles are new biomarkers of septic shock-induced disseminated intravascular coagulopathy. Intensive Care Med. 39, 1695鈥?703 (2013).CAS聽 Article聽 PubMed聽Google Scholar聽 198Soriano, A. O. et al. Levels of endothelial and platelet microparticles and their interactions with leukocytes negatively correlate with organ dysfunction and predict mortality in severe sepsis. Crit. Care Med. 33, 2540鈥?546 (2005).Article聽 PubMed聽Google Scholar聽 199Trepesch, C. et al. High intravascular tissue factor-but not extracellular microvesicles-in septic patients is associated with a high SAPS II score. J. Intensive Care 4, 34 (2016).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 200Joop, K. et al. Microparticles from patients with multiple organ dysfunction syndrome and sepsis support coagulation through multiple mechanisms. Thromb. Haemost. 85, 810鈥?20 (2001).CAS聽 Article聽 PubMed聽Google Scholar聽 201Nieuwland, R. et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 95, 930鈥?35 (2000).CAS聽 PubMed聽Google Scholar聽 202Timar, C. I. et al. Antibacterial effect of microvesicles released from human neutrophilic granulocytes. Blood 121, 510鈥?18 (2013).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 203Oehmcke, S. et al. A novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes. PLoS Pathog. 9, e1003529 (2013).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 204Mortaza, S. et al. Detrimental hemodynamic and inflammatory effects of microparticles originating from septic rats. Crit. Care Med. 37, 2045鈥?050 (2009).CAS聽 Article聽 PubMed聽Google Scholar聽 205Meziani, F., Delabranche, X., Asfar, P. Toti, F. Bench-to-bedside review: circulating microparticles 鈥?a new player in sepsis? Crit. Care 14, 236 (2010).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 206Camussi, G., Cantaluppi, V., Deregibus, M. C., Gatti, E. Tetta, C. Role of microvesicles in acute kidney injury. Contrib. Nephrol. 174, 191鈥?99 (2011).Article聽 PubMed聽Google Scholar聽 207Bruno, S. Camussi, G. Isolation and characterization of resident mesenchymal stem cells in human glomeruli. Methods Mol. Biol. 879, 367鈥?80 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 208Akyurekli, C. et al. A systematic review of preclinical studies on the therapeutic potential of mesenchymal stromal cell-derived microvesicles. Stem Cell Rev. 11, 150鈥?60 (2015).CAS聽 Article聽Google Scholar聽 209He, J. et al. Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model. Nephrology (Carlton) 17, 493鈥?00 (2012).Article聽Google Scholar聽 210Biancone, L., Bruno, S., Deregibus, M. C., Tetta, C. Camussi, G. Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol. Dial. Transplant. 27, 3037鈥?042 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 211Bianchi, F., Sala, E., Donadei, C., Capelli, I. La Manna, G. Potential advantages of acute kidney injury management by mesenchymal stem cells. World J. Stem Cells 6, 644鈥?50 (2014).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 212Camussi, G., Deregibus, M. C., Bruno, S., Cantaluppi, V. Biancone, L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int. 78, 838鈥?48 (2010). An excellent review about how microvesicles transfer information between cells.CAS聽 Article聽 PubMed聽Google Scholar聽 213Eirin, A. et al. Comparative proteomic analysis of extracellular vesicles isolated from porcine adipose tissue-derived mesenchymal stem/stromal cells. Sci. Rep. 6, 36120 (2016).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 214Ju, G. Q. et al. Microvesicles derived from human umbilical cord mesenchymal stem cells facilitate tubular epithelial cell dedifferentiation and growth via hepatocyte growth factor induction. PLoS ONE 10, e0121534 (2015).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 215Tomasoni, S. et al. Transfer of growth factor receptor mRNA via exosomes unravels the regenerative effect of mesenchymal stem cells. Stem Cells Dev. 22, 772鈥?80 (2013).CAS聽 Article聽 PubMed聽Google Scholar聽 216Wang, Y., Lu, X., He, J. Zhao, W. Influence of erythropoietin on microvesicles derived from mesenchymal stem cells protecting renal function of chronic kidney disease. Stem Cell Res. Ther. 6, 100 (2015).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 217Hao, S., Yuan, J. Xiang, J. Nonspecific CD4+ T cells with uptake of antigen-specific dendritic cell-released exosomes stimulate antigen-specific CD8+ CTL responses and long-term T cell memory. J. Leukoc. Biol. 82, 829鈥?38 (2007).CAS聽 Article聽 PubMed聽Google Scholar聽 218Montecalvo, A. et al. Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition. J. Immunol. 180, 3081鈥?090 (2008).CAS聽 Article聽 PubMed聽Google Scholar聽 219Grange, C. et al. Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a model of acute kidney injury monitored by optical imaging. Int. J. Mol. Med. 33, 1055鈥?063 (2014).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 220Gatti, S. et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol. Dial. Transplant. 26, 1474鈥?483 (2011).CAS聽 Article聽 PubMed聽Google Scholar聽 221Bonventre, J. V. Microvesicles from mesenchymal stromal cells protect against acute kidney injury. J. Am. Soc. Nephrol. 20, 927鈥?28 (2009).Article聽 PubMed聽Google Scholar聽 222Cantaluppi, V. et al. Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells. Kidney Int. 82, 412鈥?27 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 223Herrera Sanchez, M. B. et al. Human liver stem cells and derived extracellular vesicles improve recovery in a murine model of acute kidney injury. Stem Cell Res. Ther. 5, 124 (2014).Article聽 CAS聽 PubMed聽Google Scholar聽 224Ando, M. et al. Circulating platelet-derived microparticles with procoagulant activity may be a potential cause of thrombosis in uremic patients. Kidney Int. 62, 1757鈥?763 (2002).Article聽 PubMed聽Google Scholar聽 225Burton, J. O. et al. Elevated levels of procoagulant plasma microvesicles in dialysis patients. PLoS ONE 8, e72663 (2013).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 226Amabile, N. et al. Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. J. Am. Soc. Nephrol. 16, 3381鈥?388 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 227Trappenburg, M. C. et al. Chronic renal failure is accompanied by endothelial activation and a large increase in microparticle numbers with reduced procoagulant capacity. Nephrol. Dial. Transplant. 27, 1446鈥?453 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 228Amabile, N., Guerin, A. P., Tedgui, A., Boulanger, C. M. London, G. M. Predictive value of circulating endothelial microparticles for cardiovascular mortality in end-stage renal failure: a pilot study. Nephrol. Dial. Transplant. 27, 1873鈥?880 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 229Boulanger, C. M. et al. In vivo shear stress determines circulating levels of endothelial microparticles in end-stage renal disease. Hypertension 49, 902鈥?08 (2007).CAS聽 Article聽 PubMed聽Google Scholar聽 230Lv, L. L. et al. MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis. Am. J. Physiol. Renal Physiol. 305, F1220鈥揊1227 (2013).CAS聽 Article聽 PubMed聽Google Scholar聽 231Lv, L. L. et al. CD2AP mRNA in urinary exosome as biomarker of kidney disease. Clin. Chim. Acta 428, 26鈥?1 (2014).CAS聽 Article聽 PubMed聽Google Scholar聽 232Al-Massarani, G. et al. Kidney transplantation decreases the level and procoagulant activity of circulating microparticles. Am. J. Transplant. 9, 550鈥?57 (2009).CAS聽 Article聽 PubMed聽Google Scholar聽 233Dimuccio, V. et al. Urinary CD133+ extracellular vesicles are decreased in kidney transplanted patients with slow graft function and vascular damage. PLoS ONE 9, e104490 (2014).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 234Meehan, S. M. et al. Platelets and capillary injury in acute humoral rejection of renal allografts. Hum. Pathol. 34, 533鈥?40 (2003).CAS聽 Article聽 PubMed聽Google Scholar聽 235Cumpelik, A. et al. Mechanism of platelet activation and hypercoagulability by antithymocyte globulins (ATG). Am. J. Transplant. 15, 2588鈥?601 (2015).CAS聽 Article聽 PubMed聽Google Scholar聽 236Renner, B. et al. Cyclosporine induces endothelial cell release of complement-activating microparticles. J. Am. Soc. Nephrol. 24, 1849鈥?862 (2013).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 237Matignon, M. et al. Urinary cell mRNA profiles and differential diagnosis of acute kidney graft dysfunction. J. Am. Soc. Nephrol. 25, 1586鈥?597 (2014).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 238Lorenzen, J. M. et al. Long noncoding RNAs in urine are detectable and may enable early detection of acute T cell-mediated rejection of renal allografts. Clin. Chem. 61, 1505鈥?514 (2015).CAS聽 Article聽 PubMed聽Google Scholar聽 239Pisitkun, T., Gandolfo, M. T., Das, S., Knepper, M. A. Bagnasco, S. M. Application of systems biology principles to protein biomarker discovery: urinary exosomal proteome in renal transplantation. Proteomics Clin. Appl. 6, 268鈥?78 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 240Alvarez, S. et al. Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation. Transplant. Proc. 45, 3719鈥?723 (2013).CAS聽 Article聽 PubMed聽Google Scholar聽 241Peake, P. W. et al. A comparison of the ability of levels of urinary biomarker proteins and exosomal mRNA to predict outcomes after renal transplantation. PLoS ONE 9, e98644 (2014).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 242Sonoda, H. et al. Decreased abundance of urinary exosomal aquaporin-1 in renal ischemia-reperfusion injury. Am. J. Physiol. Renal Physiol. 297, F1006鈥揊1016 (2009).CAS聽 Article聽 PubMed聽Google Scholar聽 243Becker, A. et al. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell 30, 836鈥?48 (2016).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 244Janas, A. M., Sapon, K., Janas, T., Stowell, M. H. Janas, T. Exosomes and other extracellular vesicles in neural cells and neurodegenerative diseases. Biochim.Biophys. Acta 1858, 1139鈥?151 (2016).CAS聽 Article聽 PubMed聽Google Scholar聽 245Khalyfa, A. et al. Extracellular microvesicle microRNAs in children with sickle cell anaemia with divergent clinical phenotypes. Br. J. Haematol. 174, 786鈥?98 (2016).CAS聽 Article聽 PubMed聽Google Scholar聽 246Gilani, S. I., Weissgerber, T. L., Garovic, V. D. Jayachandran, M. Preeclampsia and extracellular vesicles. Curr. Hypertens. Rep. 18, 68 (2016).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 247Sellam, J. et al. Increased levels of circulating microparticles in primary Sjogren\'s syndrome, systemic lupus erythematosus and rheumatoid arthritis and relation with disease activity. Arthritis Res. Ther. 11, R156 (2009).Article聽 CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 248Aatonen, M., Gronholm, M. Siljander, P. R. Platelet-derived microvesicles: multitalented participants in intercellular communication. Semin. Thromb. Hemost. 38, 102鈥?13 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 249Nielsen, C. T., Ostergaard, O., Johnsen, C., Jacobsen, S. Heegaard, N. H. Distinct features of circulating microparticles and their relationship to clinical manifestations in systemic lupus erythematosus. Arthritis Rheum. 63, 3067鈥?077 (2011).Article聽 PubMed聽Google Scholar聽 250Nielsen, C. T. et al. Increased IgG on cell-derived plasma microparticles in systemic lupus erythematosus is associated with autoantibodies and complement activation. Arthritis Rheum. 64, 1227鈥?236 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 251Nielsen, C. T., Rasmussen, N. S., Heegaard, N. H. Jacobsen, S. 鈥淜ill鈥?the messenger: targeting of cell-derived microparticles in lupus nephritis. Autoimmun. Rev. 15, 719鈥?25 (2016).CAS聽 Article聽 PubMed聽Google Scholar聽 252Sole, C., Cortes-Hernandez, J., Felip, M. L., Vidal, M. Ordi-Ros, J. miR-29c in urinary exosomes as predictor of early renal fibrosis in lupus nephritis. Nephrol. Dial. Transplant. 30, 1488鈥?496 (2015).CAS聽 Article聽 PubMed聽Google Scholar聽 253Knijff-Dutmer, E. A., Koerts, J., Nieuwland, R., Kalsbeek-Batenburg, E. M. van de Laar, M. A. Elevated levels of platelet microparticles are associated with disease activity in rheumatoid arthritis. Arthritis Rheum. 46, 1498鈥?503 (2002).CAS聽 Article聽 PubMed聽Google Scholar聽 254Boilard, E. et al. Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 327, 580鈥?83 (2010).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 255Rectenwald, J. E. et al. D-Dimer, P-selectin, and microparticles: novel markers to predict deep venous thrombosis. A pilot study. Thromb. Haemost. 94, 1312鈥?317 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 256Chirinos, J. A. et al. Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J. Am. Coll. Cardiol. 45, 1467鈥?471 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 257Campello, E., Spiezia, L., Radu, C. M. Simioni, P. Microparticles as biomarkers of venous thromboembolic events. Biomark. Med. 10, 743鈥?55 (2016).CAS聽 Article聽 PubMed聽Google Scholar聽 258Bal, L. et al. Factors influencing the level of circulating procoagulant microparticles in acute pulmonary embolism. Arch. Cardiovasc. Dis. 103, 394鈥?03 (2010).Article聽 PubMed聽Google Scholar聽 259Dignat-George, F. et al. Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome. Thromb. Haemost. 91, 667鈥?73 (2004).CAS聽 Article聽 PubMed聽Google Scholar聽 260Pericleous, C., Giles, I. Rahman, A. Are endothelial microparticles potential markers of vascular dysfunction in the antiphospholipid syndrome? Lupus 18, 671鈥?75 (2009).CAS聽 Article聽 PubMed聽Google Scholar聽 261Brodsky, R. A. Paroxysmal nocturnal hemoglobinuria. Blood 124, 2804鈥?811 (2014).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 262Helley, D. et al. Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab. Haematologica 95, 574鈥?81 (2010).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 263Angelillo-Scherrer, A. Leukocyte-derived microparticles in vascular homeostasis. Circ. Res. 110, 356鈥?69 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 264Leroyer, A. S., Tedgui, A. Boulanger, C. M. Role of microparticles in atherothrombosis. J. Intern. Med. 263, 528鈥?37 (2008).CAS聽 Article聽 PubMed聽Google Scholar聽 265Rautou, P. E. et al. Microparticles, vascular function, and atherothrombosis. Circ. Res. 109, 593鈥?06 (2011).CAS聽 Article聽 PubMed聽Google Scholar聽 266Owens, A. P. III Mackman, N. Microparticles in hemostasis and thrombosis. Circ. Res. 108, 1284鈥?297 (2011).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 267Lakhter, A. J. Sims, E. K. Minireview: emerging roles for extracellular vesicles in diabetes and related metabolic disorders. Mol. Endocrinol. 29, 1535鈥?548 (2015).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 268Omoto, S. et al. Detection of monocyte-derived microparticles in patients with type II diabetes mellitus. Diabetologia 45, 550鈥?55 (2002).CAS聽 Article聽 PubMed聽Google Scholar聽 269Nomura, S. Dynamic role of microparticles in type 2 diabetes mellitus. Curr. Diabetes Rev. 5, 245鈥?51 (2009).CAS聽 Article聽 PubMed聽Google Scholar聽 270Sabatier, F. et al. Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. Diabetes 51, 2840鈥?845 (2002).CAS聽 Article聽 PubMed聽Google Scholar聽 271Diamant, M. et al. Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus. Circulation 106, 2442鈥?447 (2002).CAS聽 Article聽 PubMed聽Google Scholar聽 272Chen, Y., Feng, B., Li, X., Ni, Y. Luo, Y. Plasma endothelial microparticles and their correlation with the presence of hypertension and arterial stiffness in patients with type 2 diabetes. J. Clin. Hypertens. (Greenwich) 14, 455鈥?60 (2012).CAS聽 Article聽Google Scholar聽 273Zubiri, I. et al. Kidney tissue proteomics reveals regucalcin downregulation in response to diabetic nephropathy with reflection in urinary exosomes. Transl Res. 166, 474鈥?84.e4 (2015).CAS聽 Article聽 PubMed聽Google Scholar聽 274Johansson, H. et al. Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation. Diabetes 54, 1755鈥?762 (2005).CAS聽 Article聽 PubMed聽Google Scholar聽 275Ueba, T. et al. Level, distribution and correlates of platelet-derived microparticles in healthy individuals with special reference to the metabolic syndrome. Thromb. Haemost. 100, 280鈥?85 (2008).CAS聽 Article聽 PubMed聽Google Scholar聽 276Murakami, T. et al. Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity. Thromb. Res. 119, 45鈥?3 (2007).CAS聽 Article聽 PubMed聽Google Scholar聽 277Heinrich, L. F., Andersen, D. K., Cleasby, M. E. Lawson, C. Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells. Br. J. Nutr. 113, 1704鈥?711 (2015).CAS聽 Article聽 PubMed聽Google Scholar聽 278Stepanian, A. et al. Microparticle increase in severe obesity: not related to metabolic syndrome and unchanged after massive weight loss. Obesity (Silver Spring) 21, 2236鈥?243 (2013).CAS聽 Article聽Google Scholar聽 279Agouni, A. et al. Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome. Am. J. Pathol. 173, 1210鈥?219 (2008).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 280Arteaga, R. B. et al. Endothelial microparticles and platelet and leukocyte activation in patients with the metabolic syndrome. Am. J. Cardiol. 98, 70鈥?4 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 281Little, K. M., Smalley, D. M., Harthun, N. L. Ley, K. The plasma microparticle proteome. Semin. Thromb. Hemost. 36, 845鈥?56 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 282Karolina, D. S. et al. Circulating miRNA profiles in patients with metabolic syndrome. J. Clin. Endocrinol. Metab. 97, E2271鈥揈2276 (2012).CAS聽 Article聽 PubMed聽Google Scholar聽 283Preston, R. A. et al. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension 41, 211鈥?17 (2003).CAS聽 Article聽 PubMed聽Google Scholar聽 284Wang, J. M. et al. Elevated circulating endothelial microparticles and brachial-ankle pulse wave velocity in well-controlled hypertensive patients. J. Hum. Hypertens. 23, 307鈥?15 (2009).Article聽 PubMed聽Google Scholar聽 285Huang, P. H. et al. Increased circulating CD31+/annexin V+ apoptotic microparticles and decreased circulating endothelial progenitor cell levels in hypertensive patients with microalbuminuria. J. Hypertens. 28, 1655鈥?665 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 286Kwon, S. H. et al. Elevated urinary podocyte-derived extracellular microvesicles in renovascular hypertensive patients. Nephrol. Dial. Transplant. 32, 800鈥?07 (2016).PubMed Central聽Google Scholar聽 287Wahlgren, J. et al. Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res. 40, e130 (2012).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 288Ohno, S. I. et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol. Ther. 21, 185鈥?91 (2013).CAS聽 Article聽 PubMed聽Google Scholar聽 289Alvarez-Erviti, L. et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29, 341鈥?45 (2011).CAS聽 Article聽 PubMed聽Google Scholar聽 290Tian, Y. et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 35, 2383鈥?390 (2014).CAS聽 Article聽 PubMed聽Google Scholar聽 291Johnsen, K. B. et al. A comprehensive overview of exosomes as drug delivery vehicles 鈥?endogenous nanocarriers for targeted cancer therapy. Biochim. Biophys. Acta 1846, 75鈥?7 (2014).CAS聽 PubMed聽Google Scholar聽 292Pitt, J. M. et al. Dendritic cell-derived exosomes for cancer therapy. J. Clin. Invest. 126, 1224鈥?232 (2016).Article聽 PubMed聽 PubMed Central聽Google Scholar聽 293Lener, T. et al. Applying extracellular vesicles based therapeutics in clinical trials 鈥?an ISEV position paper. J. Extracell. Vesicles 4, 30087 (2015).Article聽 CAS聽 PubMed聽Google Scholar聽 294Rand, M. L., Wang, H., Bang, K. W., Packham, M. A. Freedman, J. Rapid clearance of procoagulant platelet-derived microparticles from the circulation of rabbits. J. Thromb. Haemost. 4, 1621鈥?623 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 295Morel, O. et al. Procoagulant microparticles: disrupting the vascular homeostasis equation? Arterioscler. Thromb. Vasc. Biol. 26, 2594鈥?604 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 296Nomura, S., Kanazawa, S. Fukuhara, S. Effects of efonidipine on platelet and monocyte activation markers in hypertensive patients with and without type 2 diabetes mellitus. J. Hum. Hypertens. 16, 539鈥?47 (2002).CAS聽 Article聽 PubMed聽Google Scholar聽 297Nomura, S. et al. Probucol and ticlopidine: effect on platelet and monocyte activation markers in hyperlipidemic patients with and without type 2 diabetes. Atherosclerosis 174, 329鈥?35 (2004).CAS聽 Article聽 PubMed聽Google Scholar聽 298Nomura, S. et al. The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients. Platelets 20, 16鈥?2 (2009).CAS聽 Article聽 PubMed聽Google Scholar聽 299Nomura, S. et al. Effects of eicosapentaenoic acid on endothelial cell-derived microparticles, angiopoietins and adiponectin in patients with type 2 diabetes. J. Atheroscler. Thromb. 16, 83鈥?0 (2009).CAS聽 Article聽 PubMed聽Google Scholar聽 300Esposito, K., Ciotola, M. Giugliano, D. Pioglitazone reduces endothelial microparticles in the metabolic syndrome. Arterioscler. Thromb. Vasc. Biol. 26, 1926 (2006).CAS聽 Article聽 PubMed聽Google Scholar聽 301Yano, Y. et al. The effects of calpeptin (a calpain specific inhibitor) on agonist induced microparticle formation from the platelet plasma membrane. Thromb. Res. 71, 385鈥?96 (1993).CAS聽 Article聽 PubMed聽Google Scholar聽 302Zafrani, L. et al. Calpastatin controls polymicrobial sepsis by limiting procoagulant microparticle release. Am. J. Respir. Crit. Care Med. 185, 744鈥?55 (2012).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 303Iero, M. et al. Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ. 15, 80鈥?8 (2008).CAS聽 Article聽 PubMed聽Google Scholar聽 304Chalmin, F. et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J. Clin. Invest. 120, 457鈥?71 (2010).CAS聽 PubMed聽 PubMed Central聽Google Scholar聽 305Faille, D. et al. Endocytosis and intracellular processing of platelet microparticles by brain endothelial cells. J. Cell. Mol. Med. 16, 1731鈥?738 (2012).CAS聽 Article聽 PubMed聽 PubMed Central聽Google Scholar聽 306Barres, C. et al. Galectin-5 is bound onto the surface of rat reticulocyte exosomes and modulates vesicle uptake by macrophages. Blood 115, 696鈥?05 (2010).CAS聽 Article聽 PubMed聽Google Scholar聽 Download referencesAcknowledgementsThe authors gratefully acknowledge R. Tati (Department of Pediatrics, Lund University, Sweden) for help with figures 1 and 2. They are also grateful for funding from The Swedish Research Council (K2013-64X-14008-13-5 and K2015- 99X-22877-01-6), The Knut and Alice Wallenberg Foundation (Wallenberg Clinical Scholar 2015.0320), The Torsten S枚derberg Foundation, Sk氓ne Centre of Excellence in Health, Crown Princess Lovisa\'s Society for Child Care, Region Sk氓ne and The Konung Gustaf V:s 80-氓rsfond.Author informationAffiliationsDepartment of Pediatrics, Clinical Sciences Lund, Lund University, Klinikgatan 28, Lund, 22184, SwedenDiana Karpman,聽Anne-lie St氓hl聽 聽Ida ArvidssonAuthorsDiana KarpmanView author publicationsYou can also search for this author in PubMed聽Google ScholarAnne-lie St氓hlView author publicationsYou can also search for this author in PubMed聽Google ScholarIda ArvidssonView author publicationsYou can also search for this author in PubMed聽Google ScholarContributionsAll authors contributed to researching data for the article, discussion of the content, and revising or editing the manuscript before submission.Corresponding authorCorrespondence to Diana Karpman.Ethics declarations Competing interests The authors declare no competing financial interests. 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