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Aug 23, 2016

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EV literature (RSS feed from PubMed)

Search terms: exosomes OR "extracellular vesicles" OR microvesicles OR microparticles. Direct link to the PubMed search here.

Monocyte-Platelet Complexes in Myocardial Infarction: Sub-Sets and Platelet-Derived Microvesicles Matter.

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Monocyte-Platelet Complexes in Myocardial Infarction: Sub-Sets and Platelet-Derived Microvesicles Matter.

Thromb Haemost. 2018 Oct 17;:

Authors: Badimon L

Abstract

PMID: 30332698 [PubMed - as supplied by publisher]

Diverse Long RNAs Are Differentially Sorted into Extracellular Vesicles Secreted by Colorectal Cancer Cells.

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Diverse Long RNAs Are Differentially Sorted into Extracellular Vesicles Secreted by Colorectal Cancer Cells.

Cell Rep. 2018 Oct 16;25(3):715-725.e4

Authors: Hinger SA, Cha DJ, Franklin JL, Higginbotham JN, Dou Y, Ping J, Shu L, Prasad N, Levy S, Zhang B, Liu Q, Weaver AM, Coffey RJ, Patton JG

Abstract
The regulation and functional roles of secreted coding and long noncoding RNAs (lncRNAs; >200 nt) are largely unknown. We previously showed that mutant KRAS colorectal cancer (CRC) cells release extracellular vesicles (EVs) containing distinct proteomes, microRNAs (miRNAs), and circular RNAs. Here, we comprehensively identify diverse classes of CRC extracellular long RNAs secreted in EVs and demonstrate differential export of specific RNAs. Distinct noncoding RNAs, including antisense transcripts and transcripts derived from pseudogenes, are enriched in EVs compared to cellular profiles. We detected strong enrichment of Rab13 in mutant KRAS EVs and demonstrate functional delivery of Rab13 mRNA to recipient cells. To assay functional transfer of lncRNAs, we implemented a CRISPR/Cas9-based RNA-tracking system to monitor delivery to recipient cells. We show that gRNAs containing export signals from secreted RNAs can be transferred from donor to recipient cells. Our data support the existence of cellular mechanisms to selectively export diverse classes of RNA.

PMID: 30332650 [PubMed - in process]

Human Fetal Liver Mesenchymal Stem Cell derived Exosomes impair NK cell function.

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Human Fetal Liver Mesenchymal Stem Cell derived Exosomes impair NK cell function.

Stem Cells Dev. 2018 Oct 17;:

Authors: Ye F, Herr F, Vernochet A, Menneson B, Oberlin E, Durrbach A

Abstract
Mesenchymal stem cells (MSCs) are powerful immunomodulators that regulate the diverse functions of immune cells involved in allogeneic reactions, such as T cells and natural killer cells (NK), through cell-cell contact or secreted factors. Exosomes secreted by MSCs may be involved in their regulatory functions, providing new therapeutic tools. Here, we showed that fetal liver (FL) MSC-derived exosomes inhibit proliferation, activation, and cytotoxicity of NK cells. Exosomes bearing LAP, TGFβ, and TSP1, a regulatory molecule for TGFβ, induced downstream TGFβ/Smad2/3 signaling in NK cells. The inhibition of TGFβ using a neutralizing anti-TGFβ antibody, restored NK proliferation, differentiation, and cytotoxicity, demonstrating that FL-MSC-derived exosomes exert their inhibition on NK cell function via TGFβ. These results suggest that FL-MSC-derived exosomes regulate NK cell functions through exosome associated TGFβ.

PMID: 30328799 [PubMed - as supplied by publisher]

Extracellular Vesicles: How Drug and Pathology Interfere With Their Biogenesis and Function.

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Extracellular Vesicles: How Drug and Pathology Interfere With Their Biogenesis and Function.

Front Physiol. 2018;9:1394

Authors: Cesselli D, Parisse P, Aleksova A, Veneziano C, Cervellin C, Zanello A, Beltrami AP

Abstract
Extracellular vesicles (EV) are at the center of an intense activity of investigation, both for their possible employment as biomarkers of ongoing pathologic processes and for their broad range of biological activities. EV can promote tissue repair in very different pathologic settings, including hindlimb and myocardial ischemia. Importantly, the exact mode of action of EV is still partly understood, since they may act by modulating growth factors and cytokines, signaling pathways, and by transferring non-coding RNAs to target cells. However, the term EV identifies cell derived, enveloped particles very heterogeneous in size, composition, and biogenesis. Therefore, part of the controversies on the biological effects exerted by EV is a consequence of differences in methods of separation that result in the enrichment of different entities. Since technical challenges still hamper the highly specific sorting of different EV subpopulations, up to now only few investigators have tried to verify differences in the biological effects of specific EV subtypes. This review summarizes the current state of the art on the comprehension of mechanisms involved in EV biogenesis and release, which is a prerequisite for understanding and investigating the impact that pathology and drug therapy may exert on the secretion and composition of EV. Finally, we described both the mechanism involved in the modulation of EV secretion by drugs commonly used in patients affected by heart failure, and how pathophysiological mechanisms involved in heart disease modify EV secretion.

PMID: 30327618 [PubMed]

Cancer exosomes induce tumor innervation.

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Cancer exosomes induce tumor innervation.

Nat Commun. 2018 Oct 16;9(1):4284

Authors: Madeo M, Colbert PL, Vermeer DW, Lucido CT, Cain JT, Vichaya EG, Grossberg AJ, Muirhead D, Rickel AP, Hong Z, Zhao J, Weimer JM, Spanos WC, Lee JH, Dantzer R, Vermeer PD

Abstract
Patients with densely innervated tumors suffer with increased metastasis and decreased survival as compared to those with less innervated tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells as an in vitro neuronal model, human tumor samples and murine in vivo models to test this hypothesis. When appropriately stimulated, PC12 cells extend processes, called neurites. We show that patient tumors release vesicles, called exosomes, which induce PC12 neurite outgrowth. Using a cancer mouse model, we show that tumors compromised in exosome release are less innervated than controls. Moreover, in vivo pharmacological blockade of exosome release similarly attenuates tumor innervation. We characterize these nerves as sensory in nature and demonstrate that axonogenesis is potentiated by the exosome-packaged axonal guidance molecule, EphrinB1. These findings indicate that tumor released exosomes induce tumor innervation and exosomes containing EphrinB1 potentiate this activity.

PMID: 30327461 [PubMed - in process]

Mass spectrometry-based investigation of measles and mumps virus proteome.

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Mass spectrometry-based investigation of measles and mumps virus proteome.

Virol J. 2018 Oct 16;15(1):160

Authors: Sviben D, Forcic D, Halassy B, Allmaier G, Marchetti-Deschmann M, Brgles M

Abstract
BACKGROUND: Measles (MEV) and mumps virus (MUV) are enveloped, non-segmented, negative single stranded RNA viruses of the family Paramyxoviridae, and are the cause of measles and mumps, respectively, both preventable by vaccination. Aside from proteins coded by the viral genome, viruses are considered to contain host cell proteins (HCPs). The presence of extracellular vesicles (ECVs), which are often co-purified with viruses due to their similarity in size, density and composition, also contributes to HCPs detected in virus preparations, and this has often been neglected. The aim was to identify which virus-coded proteins are present in MEV and MUV virions, and to try to detect which HCPs, if any, are incorporated inside the virions or adsorbed on their outer surface, and which are more likely to be a contamination from co-purified ECVs.
METHODS: MUV, MEV and ECVs were purified by ultracentrifugation, hydrophobic interaction chromatography and immunoaffinity chromatography, proteins in the samples were resolved by SDS-PAGE and subjected to identification by MALDI-TOF/TOF-MS. A comparative analysis of HCPs present in all samples was carried out.
RESULTS: By proteomics approach, it was verified that almost all virus-coded proteins are present in MEV and MUV particles. Protein C in MEV which was until now considered to be non-structural viral protein, was found to be present inside the MeV virions. Results on the presence of HCPs in differently purified virus preparations imply that actin, annexins, cyclophilin A, moesin and integrin β1 are part of the virions.
CONCLUSIONS: All HCPs detected in the viruses are present in ECVs as well, indicating their possible function in vesicle formation, or that most of them are only present in ECVs. Only five HCPs were constantly present in purified virus preparations, regardless of the purification method used, implying they are likely the integral part of the virions. The approach described here is helpful for further investigation of HCPs in other virus preparations.

PMID: 30326905 [PubMed - in process]

Recent advancements in the use of exosomes as drug delivery systems.

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Recent advancements in the use of exosomes as drug delivery systems.

J Nanobiotechnology. 2018 Oct 16;16(1):81

Authors: Bunggulawa EJ, Wang W, Yin T, Wang N, Durkan C, Wang Y, Wang G

Abstract
Extracellular vesicles (EVs) are the substances that are released by most types of cells and have an important role in cell to cell communication. Among the most highly researched EVs are exosome. Recent studies show that exosomes derived from cells have different roles and targets. Many studies show that exosome can efficiently deliver many different kinds of cargo to the target cell. Therefore, they are often used to deliver therapeutic cargo for treatment. The exosomes that have been used include both natural ones and those that have been modified with other substances to increase the delivery ability. This article provides a review of both exosomes derived from various cells and modified exosome and their ability in delivering the many kinds of cargo to the target cell.

PMID: 30326899 [PubMed - in process]

Understanding extracellular vesicle diversity - current status.

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Understanding extracellular vesicle diversity - current status.

Expert Rev Proteomics. 2018 Oct 16;:

Authors: Greening DW, Simpson RJ

Abstract
INTRODUCTION: Extracellular vesicles (EVs) represent an important mode of intercellular communication. There is now a growing awareness that predominant EV subtypes; exosomes from endosomal origin, and shed microvesicles from plasma membrane budding, can be further stratified into distinct subtypes, however specific approaches in their isolation and markers that allow them to be discriminated are lacking. Areas covered: Knowledge about these distinct EV subpopulations is important including the regulation of composition, release, targeting/localisation, uptake and function. This review discusses the mechanisms of distinct EV biogenesis and release, defining select EV classes (and subpopulations), which will be crucial for development of EV-based functions and clinical applications. We review the dynamics of cargo sorting leading to the mechanisms of EV heterogeneity, their mechanisms of formation, intracellular trafficking pathways, and provide an uptake about biochemical/functional differences. With advances in purification strategies and proteomic-based quantitation, allows significant benefit in accurately describing differences in EV protein cargo composition and modification. Expert commentary: The advent of quantitative mass spectrometry (MS)-based proteomics, in conjunction with advances in molecular cell biology, and EV purification strategies, has contributed significantly to our improved characterisation and understanding of the molecular composition and functionality of these distinct EV subpopulations.

PMID: 30326765 [PubMed - as supplied by publisher]

NANOmetric BIO-Banked MSC-Derived Exosome (NANOBIOME) as a Novel Approach to Regenerative Medicine.

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NANOmetric BIO-Banked MSC-Derived Exosome (NANOBIOME) as a Novel Approach to Regenerative Medicine.

J Clin Med. 2018 Oct 15;7(10):

Authors: Codispoti B, Marrelli M, Paduano F, Tatullo M

Abstract
Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. In fact, MSCs can differentiate into several cell lineages and show paracrine behavior by releasing endogenous factors that stimulate tissue repair and modulate local immune response. Each MSC type is affected by specific biobanking issues-technical issues as well as regulatory and ethical concerns-thus making it quite tricky to safely and commonly use MSC banking for swift regenerative applications. Extracellular vesicles (EVs) include a group of 150⁻1000 nm vesicles that are released by budding from the plasma membrane into biological fluids and/or in the culture medium from varied and heterogenic cell types. EVs consist of various vesicle types that are defined with different nomenclature such as exosomes, shedding vesicles, nanoparticles, microvesicles and apoptotic bodies. Ectosomes, micro- and nanoparticles generally refer to the direct release of single vesicles from the plasma membrane. While many studies describe exosomes as deriving from multivesicular bodies, solid evidence about the origin of EVs is often lacking. Extracellular vesicles represent an important portion of the cell secretome. Their numerous properties can be used for diagnostic, prognostic, and therapeutic uses, so EVs are considered to be innovative and smart theranostic tools. The aim of this review is to investigate the usefulness of exosomes as carriers of the whole information panel characterizing the use of MSCs in regenerative medicine. Our purpose is to make a step forward in the development of the NANOmetric BIO-banked MSC-derived Exosome (NANOBIOME).

PMID: 30326618 [PubMed]

 

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