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Nicolás De Silva, Mirian Samblas, J Alfredo Martínez, Fermín I Milagro
Obesity is usually associated with low-grade inflammation, which determines the appearance of comorbidities like atherosclerosis and insulin resistance. Infiltrated macrophages in adipose tissue are partly responsible of this inflammatory condition. Numerous studies point to the existence of close intercommunication between macrophages and adipocytes and pay particular attention to the proinflammatory cytokines released by both cell types. However, it has been recently described that in both, circulation and tissue level, there are extracellular vesicles (including microvesicles and exosomes) containing miRNAs, mRNAs, and proteins that can influence the inflammatory response...
March 20, 2018: Journal of Physiology and Biochemistry
Juan Pablo Acevedo, Ioannis Angelopoulos, Danny van Noort, Maroun Khoury
Microfabrication and microfluidics contribute to the research of cellular functions of cells and their interaction with their environment. Previously, it has been shown that microfluidics can contribute to the isolation, selection, characterization and migration of cells. This review aims to provide stem cell researchers with a toolkit of microtechnology (mT) instruments for elucidating complex stem cells functions which are challenging to decipher with traditional assays and animal models. These microdevices are able to investigate about the differentiation and niche interaction, stem cells transcriptomics, therapeutic functions and the capture of their secreted microvesicles...
March 20, 2018: Regenerative Medicine
Ariel Finkielsztein, Lorraine Mascarenhas, Veronika Butin-Israeli, Ronen Sumagin
Polymorphonuclear neutrophil-derived microparticles (PMN)-MPs) are lipid bilayer, spherical microvesicles with sizes ranging from 50-1,000 nm in diameter. MPs are a newly evolving, important part of cell-to-cell communication and signaling machinery. Because of their size and the nature of their release, until recently MP existence was overlooked. However, with improved technology and analytical methods their function in health and disease is now emerging. The protocols presented here are aimed at isolating and characterizing PMN-MPs by flow cytometry and immunoblotting...
March 2, 2018: Journal of Visualized Experiments: JoVE
Ibtehaj Naqvi, Ruwan Gunaratne, Jessica E McDade, Angelo Moreno, Rachel E Rempel, Douglas C Rouse, Silvia Gabriela Herrera, David S Pisetsky, Jaewoo Lee, Rebekah R White, Bruce A Sullenger
Nucleic acid binding polymers (NABPs) have been extensively used as vehicles for DNA and RNA delivery. More recently, we discovered that a subset of these NABPs can also serve as anti-inflammatory agents by capturing pro-inflammatory extracellular nucleic acids and associated protein complexes that promote activation of toll-like receptors (TLRs) in diseases such as lupus erythematosus. Nucleic-acid-mediated TLR signaling also facilitates tumor progression and metastasis in several cancers, including pancreatic cancer (PC)...
February 23, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Lisa K Gouwens, Mudar S Ismail, Victoria A Rogers, Nathan T Zeller, Evan C Garrad, Fatima S Amtashar, Nyasha J Makoni, David C Osborn, Michael R Nichols
Microvesicles (MVs) and exosomes comprise a class of cell-secreted particles termed extracellular vesicles (EVs). These cargo-holding vesicles mediate cell-to-cell communication and have recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD). The two types of EVs are distinguished by the mechanism of cell release and their size, with the smaller exosomes and the larger MVs ranging from 30 to 100 nm and 100 nm to 1 μm in diameter, respectively. MV numbers are increased in AD and appear to interact with amyloid-β peptide (Aβ), the primary protein component of the neuritic plaques in the AD brain...
March 15, 2018: ACS Chemical Neuroscience
Xiao-Fen Ruan, Yong-Jun Li, Cheng-Wei Ju, Yan Shen, Wei Lei, Can Chen, Yang Li, Hong Yu, Yu-Tao Liu, Il-Man Kim, Xiao-Long Wang, Neal L Weintraub, Yao-Liang Tang
Suxiao Jiuxin Pill (SJP) is a traditional Chinese medicine for the treatment of acute coronary syndrome in China, which contains two principal components, tetramethylpyrazine (TMP) and borneol (BOR). Thus far, however, the molecular mechanisms underlying the beneficial effects of SJP on the cardiac microenvironment are unknown. Cardiac mesenchymal stem cells (C-MSCs) communicate with cardiomyocytes (CMs) through the release of microvesicles (exosomes) to restore cardiac homeostasis and elicit repair, in part through epigenetic regulatory mechanisms...
March 15, 2018: Acta Pharmacologica Sinica
Yohei Hisada, Charlotte Thålin, Staffan Lundström, Håkan Wallén, Nigel Mackman
INTRODUCTION: Increased levels of circulating tissue factor (TF)-positive microvesicles (MVs) may increase the risk of thrombosis. Indeed, TF-positive MVs are detected in plasma of patients with various types of diseases. In this study, we measured levels of MV TF activity in non-cancer severely ill patients and cancer patients. METHODS: We used an in-house MV TF activity assay to measure MV TF activity. RESULTS: MV TF activity was significantly increased in a population of cancer patients but not in a population of non-cancer severely ill patients compared with healthy controls...
March 7, 2018: Thrombosis Research
Yingqian Peng, Edouard Baulier, Yifeng Ke, Alejandra Young, Novruz B Ahmedli, Steven D Schwartz, Debora B Farber
Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are able to transfer their content to different target retinal cells, inducing morphological and biochemical changes in them. The main objective of this paper is to characterize EVs derived from human embryonic stem cells (hESEVs) and investigate the effects that they have on cultured retinal glial, progenitor Müller cells, which are known to give rise to retinal neurons under specific conditions...
2018: PloS One
Yoosoo Yang, Yeonsun Hong, Eunji Cho, Gi Beom Kim, In-San Kim
Membrane proteins are of great research interest, particularly because they are rich in targets for therapeutic application. The suitability of various membrane proteins as targets for therapeutic formulations, such as drugs or antibodies, has been studied in preclinical and clinical studies. For therapeutic application, however, a protein must be expressed and purified in as close to its native conformation as possible. This has proven difficult for membrane proteins, as their native conformation requires the association with an appropriate cellular membrane...
2018: Journal of Extracellular Vesicles
Somayeh Keshtkar, Negar Azarpira, Mohammad Hossein Ghahremani
Mesenchymal stem cells (MSCs) are multipotent stem cells that have gained significant attention in the field of regenerative medicine. The differentiation potential along with paracrine properties of MSCs have made them a key option for tissue repair. The paracrine functions of MSCs are applied through secreting soluble factors and releasing extracellular vesicles like exosomes and microvesicles. Extracellular vesicles are predominantly endosomal in origin and contain a cargo of miRNA, mRNA, and proteins that are transferred from their original cells to target cells...
March 9, 2018: Stem Cell Research & Therapy
Huina Zhang, Fan Yang, Yichen Guo, Li Wang, Fang Fang, Hao Wu, Shaoping Nie, Yifan Wang, Man-Lung Fung, Yu Huang, Haiteng Deng, Yanwen Qin, Xinliang Ma, Yongxiang Wei
OBJECTIVE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is an independent risk factor for many clinical complications. However, how OSAHS cause multiple organ injury and initiate inter-organ communication remains unclear. Moreover, despite it is well-recognized that chronic intermittent hypoxia (CIH) is a main feature of OSAHS, specific contribution of CIH to overall OSAHS-initiated pathological complications remains unclear. This study aimed to use an unbiased proteomic approach to determine whether OSAHS alters protein profiles of serum extracellular microvesicles (SEMVs) and how CIH contributes to such alterations...
March 6, 2018: Metabolism: Clinical and Experimental
Phimon Atsawasuwan, Paul Lazari, Yinghua Chen, Xiaofeng Zhou, Grace Viana, Carla A Evans
Secretory microRNAs (miRNAs) have been used increasingly as biomarkers for cancers, autoimmune diseases and inflammatory diseases. They are reported as being freely circulated or encapsulated in microvesicles such as exosomes. This study was performed to elucidate the presence of miRNAs with exosomes in human gingival crevicular fluid (GCF), and the expression profile of miRNA-29 during orthodontic tooth movement. Four healthy volunteer and fifteen orthodontic patients were enrolled in the study. Secretory miRNA in GCF was collected and analyzed using a bioanalyzer, realtime PCR and Western blot analysis...
2018: PloS One
Raquel Bello-Morales, Beatriz Praena, Carmen de la Nuez, María Teresa Rejas, Milagros Guerra, Marcos Galán, Manuel Izquierdo, Víctor Calvo, Claude Krummenacher, José Antonio López-Guerrero
Herpes simplex virus type 1 (HSV-1) is a neurotropic pathogen that can infect many types of cells and establishes latent infections in neurons of sensory ganglia. In some cases, the virus spreads into the CNS causing encephalitis or meningitis. Cells infected with several different types of viruses may secrete microvesicles containing viral proteins and RNAs. In some instances, extracellular microvesicles harboring infectious virus have been found. Here we describe the features of shedding microvesicles released by the human oligodendroglial HOG cell line infected with HSV-1 and their participation in the viral cycle...
March 7, 2018: Journal of Virology
Qiyu Wang, Jiujiu Yu, Tatenda Kadungure, Joseph Beyene, Hong Zhang, Quan Lu
Majority of disease-modifying therapeutic targets are restricted to the intracellular space and are therefore not druggable using existing biologic modalities. The ability to efficiently deliver macromolecules inside target cells or tissues would greatly expand the current landscape of therapeutic targets for future generations of biologic drugs, but remains challenging. Here we report the use of extracellular vesicles, known as arrestin domain containing protein 1 [ARRDC1]-mediated microvesicles (ARMMs), for packaging and intracellular delivery of a myriad of macromolecules, including the tumor suppressor p53 protein, RNAs, and the genome-editing CRISPR-Cas9/guide RNA complex...
March 6, 2018: Nature Communications
Hsiu-Kuan Lin, Hsi-Hui Lin, Yu-Wei Chiou, Ching-Lung Wu, Wen-Tai Chiu, Ming-Jer Tang
Caveolin-1 (Cav1) is down-regulated during MK4 (MDCK cells harbouring inducible Ha-RasV12 gene) transformation by Ha-RasV12 . Cav1 overexpression abrogates the Ha-RasV12 -driven transformation of MK4 cells; however, the targeted down-regulation of Cav1 is not sufficient to mimic this transformation. Cav1-silenced cells, including MK4/shCav1 cells and MDCK/shCav1 cells, showed an increased cell area and discontinuous junction-related proteins staining. Cellular and mechanical transformations were completed when MDCK/shCav1 cells were treated with medium conditioned by MK4 cells treated with IPTG (MK4+I-CM) but not with medium conditioned by MK4 cells...
March 4, 2018: Journal of Cellular and Molecular Medicine
Mingrui An, Jianhui Zhu, Jing Wu, Kyle C Cuneo, David M Lubman
Circulating microvesicles are able to mediate long-distance cell-cell communications. It is essential to understand how microvesicles from pancreatic cancer act on other cells in the body. In this work, serum-derived microvesicles were isolated from 10 patients with locally advanced pancreatic cancer and healthy controls. Using Cell Transwell and WST-1 reagents, we found that microvesicles from pancreatic cancer accelerated migration and proliferation of PANC-1 cells. Meanwhile, the proliferation of these cancer microvesicles treated cells (CMTCs) was affected less by 10 µM of gemcitabine relative to healthy microvesicles treated cells (HMTCs)...
March 1, 2018: Journal of Proteome Research
Alanna E Sedgwick, Crislyn D'Souza-Schorey
The study of extracellular vesicles is a rapidly evolving field, owing in large part to recent advances in the realization of their significant contributions to normal physiology and disease. Once discredited as cell debris, these membrane vesicles have now emerged as mediators of intercellular communication by interaction with target cells, drug and gene delivery, and as potentially versatile platforms of clinical biomarkers as a result of their distinctive protein, nucleic acid, and lipid cargoes. While there are multiple classes of extracellular vesicles released from almost all cell types, here we focus primarily on the biogenesis, fate, and functional cargoes of microvesicles...
February 26, 2018: Traffic
Federico Colombo, Mattia Bastoni, Annamaria Nigro, Paola Podini, Annamaria Finardi, Giacomo Casella, Menon Ramesh, Cinthia Farina, Claudia Verderio, Roberto Furlan
Microvesicles (MVs) are membrane particles of 200-500 nm released by all cell types constitutively. MVs of myeloid origin are found increased in the cerebrospinal fluid (CSF) of patients suffering from neuroinflammatory disorders, although the factors triggering their production have never been defined. Here, we report that both pro- and anti-inflammatory cytokines, specifically interferon-γ and interleukin-4, are equally able to stimulate the production of MVs from microglia cells and monocytes. Additionally, we found this process to be independent from the best characterized molecular pathway so far described for membrane shedding, which is centered on the purinergic receptor P2X7, whose activation by high concentrations of extracellular ATP (exATP) results in membrane blebbing operated by the secreted enzyme acid sphingomyelinase (ASMase)...
2018: Frontiers in Immunology
Song Han, David H Gonzalo, Michael Feely, Carlos Rinaldi, Sayali Belsare, Haiyan Zhai, Krishan Kalra, Michael H Gerber, Christopher E Forsmark, Steven J Hughes
The biology of tumor-associated stroma (TAS) in pancreatic ductal adenocarcinoma (PDAC) is not well understood. The paradoxical observation that stroma-depletion strategies lead to progression of PDAC reinforced the need to critically evaluate the functional contribution of TAS in the initiation and progression of PDAC. PDAC and TAS cells are unique in their expression of specific miRNAs, and this specific miRNA expression pattern alters host to tumor microenvironment interactions. Using primary human pancreatic TAS cells and primary xenograft PDAC cells co-culture, we provide evidence of miRNA trafficking and exchanging between TAS and PDAC cells, in a two-way, cell-contact independent fashion, via extracellular vesicles (EVs) transportation...
January 19, 2018: Oncotarget
Katia Monastyrskaya
Cells respond to pathophysiological states by activation of stress-induced signalling. Regulatory non-coding microRNAs (miRNAs) often form stable feed-forward loops which ensure prolongation of the signal, contributing to sustained activation. Members of the annexin protein family act as sensors for Ca2+ , pH, and lipid second messengers, and regulate various signalling pathways. Recently, annexins were reported to participate in feedback loops, suppressing miRNA synthesis and attenuating stress-induced dysregulation of gene expression...
February 16, 2018: International Journal of Molecular Sciences
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