Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry Jr WT., Carter BS, Krichevsky AM, Breakefield XOGlioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10: 1470-1476

Department of Neurology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Nature Cell Biology (Impact Factor: 19.68). 12/2008; 10(12):1470-6. DOI: 10.1038/ncb1800
Source: PubMed


Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test.

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    • "FACS analysis of single cells obtained from vaginal tissues showed that human SE were internalized by murine vaginal cells in vivo within 24 h of inoculation (Fig. 4B). Following internalization, exosomes can donate functional mRNA to recipient cells (Kogure et al., 2011; Li et al., 2013; Skog et al., 2008). We used Apobec3G and Apobec3F TaqMan RT-qPCR to examine whether human SE donated Apobec3G and Apo- bec3F mRNA to mice. "
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    ABSTRACT: Exosomes are membranous extracellular nanovesicles secreted by diverse cell types. Exosomes from healthy human semen have been shown to inhibit HIV-1 replication and to impair progeny virus infectivity. In this study, we examined the ability of healthy human semen exosomes to restrict HIV-1 and LP-BM5 murine AIDS virus transmission in three different model systems. We show that vaginal cells internalize exosomes with concomitant transfer of functional mRNA. Semen exosomes blocked the spread of HIV-1 from vaginal epithelial cells to target cells in our cell-to-cell infection model and suppressed transmission of HIV-1 across the vaginal epithelial barrier in our trans-well model. Our in vivo model shows that human semen exosomes restrict intravaginal transmission and propagation of murine AIDS virus. Our study highlights an antiretroviral role for semen exosomes that may be harnessed for the development of novel therapeutic strategies to combat HIV-1 transmission. Copyright © 2015 Elsevier Inc. All rights reserved.
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    • "The RNA enclosed in EVs is protected from RNase activity (Skog et al. 2008). The addition of RNase to EV pellets reduced the RNA content by less than 7% (Skog et al. 2008, Huang et al. 2013). However, the treatment of EVs with detergent before RNase addition resulted in the removal of mRNA coding for Cre recombinase as evaluated by reverse transcription polymerase chain reaction (RT-PCR), supporting the notion that nucleic acids are protected inside EVs (Ridder et al. 2014). "
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    ABSTRACT: The release of extracellular vesicles (EVs), including exosomes and microvesicles, is a phenomenon shared by many cell types as a means of communicating with other cells and also potentially removing cell contents. The cargo of EVs includes the proteins, lipids, nucleic acids, and membrane receptors of the cells from which they originate. EVs released into the extracellular space can enter body fluids and potentially reach distant tissues. Once taken up by neighboring and/or distal cells, EVs can transfer functional cargo that may alter the status of recipient cells, thereby contributing to both physiological and pathological processes. In this article, we will focus on EV composition, mechanisms of uptake, and their biological effects on recipient cells. We will also discuss established and recently developed methods used to study EVs, including isolation, quantification, labeling and imaging protocols, as well as RNA analysis.
    Full-text · Article · Jul 2015 · BioScience
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    • "The use of electric fields, in combination with fluid flow, has been proposed as a powerful method to direct the behavior of vesicles towards a wide range of biotechnological applications. Weak electric fields have found applications in cell manipulation techniques such as electrofusion [31], tissue ablation [32], wound healing [33], and in the treatment of tumors [34]. Strong electric fields induce electro-poration in vesicles through the formation of transient pores in the membrane and could play a role in novel biotechnological advances such as the delivery of drugs and DNA into living cells [35] [36]. "
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    ABSTRACT: A three-dimensional numerical model of vesicle electrohydrodynamics in the presence of DC electric fields is presented. The vesicle membrane is modeled as a thin capacitive interface through the use of a semi-implicit level set Jet scheme. The enclosed volume and surface area are conserved both locally and globally by a new Navier-Stokes projection method. The electric field calculations explicitly take into account the capacitive interface by an implicit Immersed Interface Method formulation, which calculates the electric potential field and the trans-membrane potential simultaneously. The results match well with previously published experimental, analytic and two-dimensional computational works.
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