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Journal of Extracellular Vesicles

Jennifer Phan, Priyadarsini Kumar, Dake Hao, Kewa Gao, Diana Farmer, Aijun Wang
Through traditional medicine, there were diseases and disorders that previously remained untreated or were simply thought to be incurable. Since the discovery of mesenchymal stem cells (MSCs), there has been a flurry of research to develop MSC-based therapy for diseases and disorders. It is now well-known that MSCs do not typically engraft after transplantation and exhibit their therapeutic effect via a paracrine mechanism. In addition to secretory proteins, MSCs also produce extracellular vesicles (EVs), membrane-bound nanovesicles containing proteins, DNA and RNA...
2018: Journal of Extracellular Vesicles
Shang-Chun Guo, Shi-Cong Tao, Helen Dawn
Extracellular vesicles (EVs), which can be found in almost all body fluids, consist of a lipid bilayer enclosing proteins and nucleic acids from their cells of origin. EVs can transport their cargo to target cells and have therefore emerged as key players in intercellular communication. Their potential as either diagnostic and prognostic biomarkers or therapeutic drug delivery systems (DDSs) has generated considerable interest in recent years. However, conventional methods used to study EVs still have significant limitations including the time-consuming and low throughput techniques required, while at the same time the demand for better research tools is getting stronger and stronger...
2018: Journal of Extracellular Vesicles
Ryan M Allen, Shilin Zhao, Marisol A Ramirez Solano, Wanying Zhu, Danielle L Michell, Yuhuan Wang, Yu Shyr, Praveen Sethupathy, MacRae F Linton, Gregory A Graf, Quanhu Sheng, Kasey C Vickers
To comprehensively study extracellular small RNAs (sRNA) by sequencing (sRNA-seq), we developed a novel pipeline to overcome current limitations in analysis entitled, "Tools for Integrative Genome analysis of Extracellular sRNAs (TIGER)". To demonstrate the power of this tool, sRNA-seq was performed on mouse lipoproteins, bile, urine and livers. A key advance for the TIGER pipeline is the ability to analyse both host and non-host sRNAs at genomic, parent RNA and individual fragment levels. TIGER was able to identify approximately 60% of sRNAs on lipoproteins and >85% of sRNAs in liver, bile and urine, a significant advance compared to existing software...
2018: Journal of Extracellular Vesicles
Tatyana Vagner, Cristiana Spinelli, Valentina R Minciacchi, Leonora Balaj, Mandana Zandian, Andrew Conley, Andries Zijlstra, Michael R Freeman, Francesca Demichelis, Subhajyoti De, Edwin M Posadas, Hisashi Tanaka, Dolores Di Vizio
Cancer-derived extracellular vesicles (EVs) are membrane-enclosed structures of highly variable size. EVs contain a myriad of substances (proteins, lipid, RNA, DNA) that provide a reservoir of circulating molecules, thus offering a good source of biomarkers. We demonstrate here that large EVs (L-EV) (large oncosomes) isolated from prostate cancer (PCa) cells and patient plasma are an EV population that is enriched in chromosomal DNA, including large fragments up to 2 million base pair long. While L-EVs and small EVs (S-EV) (exosomes) isolated from the same cells contained similar amounts of protein, the DNA was more abundant in L-EV, despite S-EVs being more numerous...
2018: Journal of Extracellular Vesicles
Sylvie Cointe, Karim Harti Souab, Tarik Bouriche, Loris Vallier, Amandine Bonifay, Coralie Judicone, Stéphane Robert, Romain Armand, Philippe Poncelet, Jacques Albanese, Françoise Dignat-George, Romaric Lacroix
Among extracellular vesicles, leukocyte-derived microvesicles (LMVs) have emerged as complex vesicular structures. Primarily identified as procoagulant entities, they were more recently ascribed to plasmin generation capacity (MV-PGC). The objectives of this work were (1) to develop a new hybrid bio-assay combining the specific isolation of LMVs and measurement of their PGC, and compare its performance to the original method based on centrifugation, (2) to validate MV-PGC in septic shock, combining increased levels of LMVs and fibrinolytic imbalance...
2018: Journal of Extracellular Vesicles
C Spinelli, L Montermini, B Meehan, A R Brisson, S Tan, D Choi, I Nakano, J Rak
We have previously uncovered the impact of oncogenic and differentiation processes on extracellular vesicles (EVs) in cancer. This is of interested in the context of glioma stem cells (GSC) that are responsible for recurrent nature of glioblastoma multiforme (GBM), while retaining the potential to undergo differentiation and self renewal.  GSCs reside in vascular niches where they interact with endothelial cells through a number of mediators including bioactive cargo of EVs. GSCs can be classified as proneural (PN) or mesenchymal (MES) subtypes on the basis of their gene expression profiles and distinct biological characteristics...
2018: Journal of Extracellular Vesicles
Eline Oeyen, Kurt Van Mol, Geert Baggerman, Hanny Willems, Kurt Boonen, Christian Rolfo, Patrick Pauwels, An Jacobs, Karin Schildermans, William C Cho, Inge Mertens
Extracellular vesicles (EVs) have a great potential in clinical applications. However, their isolation from different bodily fluids and their characterisation are currently not optimal or standardised. Here, we report the results of examining the performance of ultrafiltration combined with size exclusion chromatography (UF-SEC) to isolate EVs from urine. The results reveal that UF-SEC is an efficient method and provides high purity. Furthermore, we introduce asymmetrical-flow field-flow fractionation coupled with a UV detector and multi-angle light-scattering detector (AF4/UV-MALS) as a characterisation method and compare it with current methods...
2018: Journal of Extracellular Vesicles
Andrew D Foers, Simon Chatfield, Laura F Dagley, Benjamin J Scicluna, Andrew I Webb, Lesley Cheng, Andrew F Hill, Ian P Wicks, Ken C Pang
As a complex biological fluid, human synovial fluid (SF) presents challenges for extracellular vesicle (EV) enrichment using standard methods. In this study of human SF, a size exclusion chromatography (SEC)-based method of EV enrichment is shown to deplete contaminants that remain after standard ultracentrifugation-based enrichment methods. Specifically, considerable levels of serum albumin, the high-density lipoprotein marker, apolipoprotein A-I, fibronectin and other extracellular proteins and debris are present in EVs prepared by differential ultracentrifugation...
2018: Journal of Extracellular Vesicles
Jonathan Degosserie, Charlotte Heymans, Catherine Spourquet, Mathias Halbout, Ludovic D'Auria, Patrick Van Der Smissen, Didier Vertommen, Pierre J Courtoy, Donatienne Tyteca, Christophe E Pierreux
Organogenesis is a complex and dynamic process requiring reciprocal communication between different cell types. In the thyroid, thyrocyte progenitors secrete the angiocrine factor, VEGFA, to recruit endothelial cells. In return, endothelial cells promote thyrocyte organisation into spherical follicular structures, which are responsible for thyroid hormone synthesis and storage. Medium conditioned by endothelial progenitor cells (EPCs) can promote follicle formation and lumen expansion (i.e. folliculogenesis) in an ex vivo culture system of thyroid lobes...
2018: Journal of Extracellular Vesicles
Dominik Buschmann, Benedikt Kirchner, Stefanie Hermann, Melanie Märte, Christine Wurmser, Florian Brandes, Stefan Kotschote, Michael Bonin, Ortrud K Steinlein, Michael W Pfaffl, Gustav Schelling, Marlene Reithmair
Extracellular vesicles (EVs) are intercellular communicators with key functions in physiological and pathological processes and have recently garnered interest because of their diagnostic and therapeutic potential. The past decade has brought about the development and commercialization of a wide array of methods to isolate EVs from serum. Which subpopulations of EVs are captured strongly depends on the isolation method, which in turn determines how suitable resulting samples are for various downstream applications...
2018: Journal of Extracellular Vesicles
Marc Clos-Garcia, Ana Loizaga-Iriarte, Patricia Zuñiga-Garcia, Pilar Sánchez-Mosquera, Ana Rosa Cortazar, Esperanza González, Verónica Torrano, Cristina Alonso, Miriam Pérez-Cormenzana, Aitziber Ugalde-Olano, Isabel Lacasa-Viscasillas, Azucena Castro, Felix Royo, Miguel Unda, Arkaitz Carracedo, Juan M Falcón-Pérez
Urine contains extracellular vesicles (EVs) that concentrate molecules and protect them from degradation. Thus, isolation and characterisation of urinary EVs could increase the efficiency of biomarker discovery. We have previously identified proteins and RNAs with differential abundance in urinary EVs from prostate cancer (PCa) patients compared to benign prostate hyperplasia (BPH). Here, we focused on the analysis of the metabolites contained in urinary EVs collected from patients with PCa and BPH. Targeted metabolomics analysis of EVs was performed by ultra-high-performance liquid chromatography-mass spectrometry...
2018: Journal of Extracellular Vesicles
Doan C Nguyen, Holly C Lewis, Chester Joyner, Vivien Warren, Haopeng Xiao, Haydn T Kissick, Ronghu Wu, Jacques Galipeau, F Eun-Hyung Lee
Extracellular vesicles (EVs) from bone marrow (BM)-derived mesenchymal stromal cells (BM-MSC) are novel mechanisms of cell-cell communication over short and long distances. BM-MSC have been shown to support human antibody secreting cells (ASC) survival ex vivo , but whether the crosstalk between the MSC-ASC interaction can occur via EVs is not known. Thus, we evaluated the role of EVs in ASC survival and IgG secretion. EVs were isolated from irradiated and non-irradiated primary BM-MSC and were quantified. They were further characterized by electron microscopy (EM) and CD63 and CD81 immuno-gold EM staining...
2018: Journal of Extracellular Vesicles
Kleber Silva Ribeiro, Camilla Ioshida Vasconcellos, Rodrigo Pedro Soares, Maria Tays Mendes, Cameron C Ellis, Marcela Aguilera-Flores, Igor Correia de Almeida, Sergio Schenkman, Leo Kei Iwai, Ana Claudia Torrecilhas
Trypanosoma cruzi , the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of T. cruzi , which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture-derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy...
2018: Journal of Extracellular Vesicles
Li Chen, Ruju Chen, Sherri Kemper, Min Cong, Hong You, David R Brigstock
The lack of approved therapies for hepatic fibrosis seriously limits medical management of patients with chronic liver disease. Since extracellular vesicles (EVs) function as conduits for intercellular molecular transfer, we investigated if EVs from healthy individuals have anti-fibrotic properties. Hepatic fibrogenesis or fibrosis in carbon tetrachloride (CCl4 )- or thioacetic acid-induced liver injury models in male or female mice were suppressed by serum EVs from normal mice (EVN) but not from fibrotic mice (EVF)...
2018: Journal of Extracellular Vesicles
Zhenyu Zhong, Matthew Rosenow, Nick Xiao, David Spetzler
Extracellular vesicle (EV)-based liquid biopsies have been proposed to be a readily obtainable biological substrate recently for both profiling and diagnostics purposes. Development of a fast and reliable preparation protocol to enrich such small particles could accelerate the discovery of informative, disease-related biomarkers. Though multiple EV enrichment protocols are available, in terms of efficiency, reproducibility and simplicity, precipitation-based methods are most amenable to studies with large numbers of subjects...
2018: Journal of Extracellular Vesicles
Ryan C Middleton, Russell G Rogers, Geoffrey De Couto, Eleni Tseliou, Kristin Luther, Ronald Holewinski, Daniel Soetkamp, Jennifer E Van Eyk, Travis J Antes, Eduardo Marbán
Newts can regenerate amputated limbs and cardiac tissue, unlike mammals which lack broad regenerative capacity. Several signaling pathways involved in cell proliferation, differentiation and survival during newt tissue regeneration have been elucidated, however the factors that coordinate signaling between cells, as well as the conservation of these factors in other animals, are not well defined. Here we report that media conditioned by newt limb explant cells (A1 cells) protect mammalian cardiomyocytes from oxidative stress-induced apoptosis...
2018: Journal of Extracellular Vesicles
Thøger Nielsen, Anne Flou Kristensen, Shona Pedersen, Gunna Christiansen, Søren Risom Kristensen
Tissue factor (TF) is the main initiator of coagulation and procoagulant phospholipids (PPL) are key components in promoting coagulation activity in blood. Both TF and PPL may be presented on the surface of extracellular vesicles (EVs), thus contributing to their procoagulant activity. These EVs may constitute a substantial part of pathological hypercoagulability that is responsible for triggering a higher risk of thrombosis in certain patients. The aim of this study was to describe a model system for the isolation of EVs required for investigating their effect on coagulation...
2018: Journal of Extracellular Vesicles
Mark J McVey, Christopher M Spring, Wolfgang M Kuebler
Improvements in identification and assessment of extracellular vesicles (EVs) have fuelled a recent surge in EV publications investigating their roles as biomarkers and mediators of disease. Meaningful scientific comparisons are, however, hampered by difficulties in accurate, reproducible enumeration and characterization of EVs in biological fluids. High-sensitivity flow cytometry (FCM) is presently the most commonly applied strategy to assess EVs, yet its utility is limited by variant ability to resolve smaller EVs...
2018: Journal of Extracellular Vesicles
Jesús Castro-Marrero, Esther Serrano-Pertierra, Myriam Oliveira-Rodríguez, Maria Cleofé Zaragozá, Alba Martínez-Martínez, María Del Carmen Blanco-López, José Alegre
Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME) is an acquired, complex and multisystem condition of unknown etiology, no established diagnostic lab tests and no universally FDA-approved drugs for treatment. CFS/ME is characterised by unexplicable disabling fatigue and is often also associated with numerous core symptoms. A growing body of evidence suggests that extracellular vesicles (EVs) play a role in cell-to-cell communication, and are involved in both physiological and pathological processes...
2018: Journal of Extracellular Vesicles
Jordi Berenguer, Tonny Lagerweij, Xi Wen Zhao, Sophie Dusoswa, Petra van der Stoop, Bart Westerman, Mark C de Gooijer, Marloes Zoetemelk, Anoek Zomer, Matheus H W Crommentuijn, Laurine E Wedekind, Àlan López-López, Alberta Giovanazzi, Marina Bruch-Oms, Ida H van der Meulen-Muileman, Rogier M Reijmers, Toin H van Kuppevelt, Juan-Jesús García-Vallejo, Yvette van Kooyk, Bakhos A Tannous, Pieter Wesseling, Danijela Koppers-Lalic, W Peter Vandertop, David P Noske, Victor W van Beusechem, Jacco van Rheenen, D Michiel Pegtel, Olaf van Tellingen, Thomas Wurdinger
Cancer cells release extracellular vesicles (EVs) that contain functional biomolecules such as RNA and proteins. EVs are transferred to recipient cancer cells and can promote tumour progression and therapy resistance. Through RNAi screening, we identified a novel EV uptake mechanism involving a triple interaction between the chemokine receptor CCR8 on the cells, glycans exposed on EVs and the soluble ligand CCL18. This ligand acts as bridging molecule, connecting EVs to cancer cells. We show that glioblastoma EVs promote cell proliferation and resistance to the alkylating agent temozolomide (TMZ)...
2018: Journal of Extracellular Vesicles
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