Regulation and mechanisms of extracellular vesicle biogenesis and secretion

2018 ◽  
Vol 62 (2) ◽  
pp. 125-133 ◽  
Author(s):  
Crislyn D’Souza-Schorey ◽  
Jeffrey S. Schorey

EV (extracellular vesicle) biology is a rapidly expanding field. These heterogeneous membrane vesicles, which are shed from virtually all cell types, collectively represent a new dimension of intercellular communication in normal physiology and disease. They have been shown to deliver infectious and pathogenic agents to non-infected cells whereas in cancers they are thought to condition the tumor microenvironment. Their presence in body fluids and inherent capacity for systemic delivery point to their clinical promise. All of the above only intensifies the need to better understand the classification, mode of biogenesis, and contents of the different subtypes of EVs. This article focusses on vesicle subtypes labeled as exosomes and MVs (microvesicles) and discusses the biogenesis and release of these vesicles from cells.

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 570
Author(s):  
Laura Saludas ◽  
Cláudia C. Oliveira ◽  
Carmen Roncal ◽  
Adrián Ruiz-Villalba ◽  
Felipe Prósper ◽  
...  

Extracellular vesicles (EVs) are constituted by a group of heterogeneous membrane vesicles secreted by most cell types that play a crucial role in cell–cell communication. In recent years, EVs have been postulated as a relevant novel therapeutic option for cardiovascular diseases, including myocardial infarction (MI), partially outperforming cell therapy. EVs may present several desirable features, such as no tumorigenicity, low immunogenic potential, high stability, and fine cardiac reparative efficacy. Furthermore, the natural origin of EVs makes them exceptional vehicles for drug delivery. EVs may overcome many of the limitations associated with current drug delivery systems (DDS), as they can travel long distances in body fluids, cross biological barriers, and deliver their cargo to recipient cells, among others. Here, we provide an overview of the most recent discoveries regarding the therapeutic potential of EVs for addressing cardiac damage after MI. In addition, we review the use of bioengineered EVs for targeted cardiac delivery and present some recent advances for exploiting EVs as DDS. Finally, we also discuss some of the most crucial aspects that should be addressed before a widespread translation to the clinical arena.


2016 ◽  
Author(s):  
Zhaohao Liao ◽  
Dillon C. Muth ◽  
Erez Eitan ◽  
Meghan Travers ◽  
Elin Lehrmann ◽  
...  

ABSTRACTExtracellular vesicles (EVs, including exosomes and microvesicles) are involved in intercellular communication in health and disease and affect processes including immune and antiviral responses. Ultracentrifuged serum is depleted of EVs and, when used in culture media, reduces growth and viability of some cell types. In this study, we examined the effects of serum EV depletion processes on HIV-1 replication in primary cells and cell lines, including two HIV-1 latency models. Increased HIV-1 production was observed in certain EV-depleted conditions, along with cell morphology changes and decreased cell viability. Add-back of ultracentrifuge pellets rescued baseline HIV-1 production. Primary cells appeared to be less sensitive to EV depletion. ACH-2 and U1 latency models produced more HIV-1 under EV-depleted conditions, while virus produced under processed serum conditions was more infectious. Finally, changes in cellular metabolism and gene expression were associated with EV-depleted culture. In conclusion, the EV environment of HIV-1 infected cells has a substantial effect on virus production and infectivity. EV-dependence of cell cultures should be examined carefully along with other experimental variables. However, EVs may not be the only particles depleted by ultracentrifugation or other processes. Effects of EVs may be accompanied by or confused with those of closely associated or physically similar particles.


Author(s):  
Yanhua Xu ◽  
Shan Kong ◽  
Shiyi Qin ◽  
Xianjuan Shen ◽  
Shaoqing Ju

Exosomes are a group of nano-sized membrane vesicles and are important mediators of intercellular communication, particularly in tumor microenvironment. Recently, researchers have found that circular RNAs (circRNAs), with the great research significance, are enriched and stable in exosomes. In this review, we summarize the research significance of exosomal circRNAs, sorting mechanisms and their functioning mechanisms in tumor progression. Their clinical applications as clinical tumor biomarkers and as therapeutic targets in inhibiting tumor metastasis, anti-cancer immunity response and drug resistance have been widely discussed.


2019 ◽  
Vol 6 (1) ◽  
pp. 7 ◽  
Author(s):  
Thomas Hartjes ◽  
Serhii Mytnyk ◽  
Guido Jenster ◽  
Volkert van Steijn ◽  
Martin van Royen

Extracellular vesicles (EVs) are a family of small membrane vesicles that carry information about cells by which they are secreted. Growing interest in the role of EVs in intercellular communication, but also in using their diagnostic, prognostic and therapeutic potential in (bio) medical applications, demands for accurate assessment of their biochemical and physical properties. In this review, we provide an overview of available technologies for EV analysis by describing their working principles, assessing their utility in EV research and summarising their potential and limitations. To emphasise the innovations in EV analysis, we also highlight the unique possibilities of emerging technologies with high potential for further development.


2019 ◽  
Vol 20 (24) ◽  
pp. 6109 ◽  
Author(s):  
Joseph Mills ◽  
Marina Capece ◽  
Emanuele Cocucci ◽  
Anna Tessari ◽  
Dario Palmieri

Several non-protein-coding genomic regions, previously marked as “junk DNA”, have been reported to be transcriptionally active, giving rise to non-coding RNA species implicated in fundamental biological and pathological processes. In particular, microRNAs (miRNAs), a class of small non-coding RNAs mediating post-transcriptional gene silencing, are causally involved in several human diseases, including various cancer types. Extracellular vesicles (EVs) are membranous structures physiologically released by most cell types. Initially, they were considered a “waste-removal” mechanism, through which cells could dispose unnecessary material and organelles. It is now widely demonstrated that EVs also play a critical role in intercellular communication, mediating the horizontal transfer of lipids, proteins, and genetic material. A paradigm shift in the biology of miRNAs was represented by the discovery that EVs, especially from cancer cells, contain miRs. EV-associated miRs act as autocrine, paracrine and endocrine factors, participating in cancer pathogenesis by modulating intercellular communication. Noteworthy, these formerly neglected molecules are now considered the next generation of cancer “theranostic” tools, with strong clinical relevance. In this review, we aim to summarize the most recent findings regarding EV-associated miRs in cancer pathogenesis and in the development of novel anti-neoplastic diagnostic and therapeutic approaches.


Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 225 ◽  
Author(s):  
Irène Tatischeff

Cell-derived extracellular vesicles (EVs) are newly uncovered messengers for intercellular communication. They are released by almost all cell types in the three kingdoms, Archeabacteria, Bacteria and Eukaryotes. They are known to mediate important biological functions and to be increasingly involved in cell physiology and in many human diseases, especially in oncology. The aim of this review is to recapitulate the current knowledge about EVs and to summarize our pioneering work about Dictyostelium discoideum EVs. However, many challenges remain unsolved in the EV research field, before any EV application for theranostics (diagnosis, prognosis, and therapy) of human cancers, can be efficiently implemented in the clinics. Dictyostelium might be an outstanding eukaryotic cell model for deciphering the utmost challenging problem of EV heterogeneity, and for unraveling the still mostly unknown mechanisms of their specific functions as mediators of intercellular communication.


2011 ◽  
Vol 3 (1) ◽  
pp. 18
Author(s):  
Anna Meiliana ◽  
Andi Wijaya

BACKGROUND: The prevailing view that eukaryotic cells are restrained from intercellular exchange of genetic information has been challenged by recent reports on nanotubes, exosomes, apoptotic bodies, and nucleic acid—binding peptides that provide novel pathways for cell—cell communication, with implications in health and disease.CONTENT: Microparticles (MPs) are a heterogeneous population of small plasma membrane structures that serve as important signaling structures between cells. MPs are composed of a phospholipid bilayer that exposes transmembrane proteins and receptors and encloses cytosolic components such as enzymes, transcription factors, and mRNA derived from their parent cells. Growing evidence suggests that MPs regulate inflammation, stimulate coagulation, affect vascular functions and apoptosis, and can also play a role in cell proliferation or differentiation. MPs circulate in the bloodstream, can be detected in the peripheral blood, and may originate from different vascular cell types (eg, platelets, monocytes, endothelial cells, red blood cells, and granulocytes).SUMMARY: Cells of various types release small membrane vesicles called MP on their activation, as well as during the process of apoptosis. The properties and roles of MP generated in different contexts are diverse and are determined by their parent cell and the pathway of their generation, which affects their content. MP are involved in multiple cellular functions, including immunomodulation, inflammation, coagulation, and intercellular communication. MPs are able to deliver molecular signals in the form of lipids, proteins, nucleic acids, or functional trans-membrane proteins from the parent cell to distantly located targets. From a clinical point of view, MP may serve as biomarkers for disease status and may be found useful for developing novel therapeutic strategies.KEYWORDS: microparticles, microvesicle, membrane remodeling, Intercellular communication


2021 ◽  
Vol 12 ◽  
Author(s):  
Anna Gioseffi ◽  
Mariola J. Edelmann ◽  
Peter E. Kima

Extracellular vesicles (EVs) have garnered significant interest in recent years due to their contributions to cell-to-cell communication and disease processes. EVs are composed of a complex profile of bioactive molecules, which include lipids, nucleic acids, metabolites, and proteins. Although the biogenesis of EVs released by cells under various normal and abnormal conditions has been well-studied, there is incomplete knowledge about how infection influences EV biogenesis. EVs from infected cells contain specific molecules of both host and pathogen origin that may contribute to pathogenesis and the elicitation of the host immune response. Intracellular pathogens exhibit diverse lifestyles that undoubtedly dictate the mechanisms by which their molecules enter the cell’s exosome biogenesis schemes. We will discuss the current understanding of the mechanisms used during infection to traffic molecules from their vacuolar niche to host EVs by selected intravacuolar pathogens. We initially review general exosome biogenesis schemes and then discuss what is known about EV biogenesis in Mycobacterium, Plasmodium, Toxoplasma, and Leishmania infections, which are pathogens that reside within membrane delimited compartments in phagocytes at some time in their life cycle within mammalian hosts. The review includes discussion of the need for further studies into the biogenesis of EVs to better understand the contributions of these vesicles to host-pathogen interactions, and to uncover potential therapeutic targets to control these pathogens.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1612 ◽  
Author(s):  
Whitney Longmate ◽  
C Michael DiPersio

While integrins were originally discovered as cell adhesion receptors, recent studies have reinforced the concept that integrins have central roles in cancer that extend far beyond controlling cell adhesion and migration. Indeed, as transmembrane cell surface receptors that occupy a critical position at the interface of cellular and extracellular interactions and are capable of both “inside-out” and “outside-in” signaling, integrins are uniquely poised to regulate the cell’s ability to promote, sense, and react to changes in the tumor microenvironment. Moreover, integrins are present on all cell types in the tumor microenvironment, and they have important roles in regulating intercellular communication. Decades of promising pre-clinical studies have implicated certain integrins as attractive therapeutic targets in the cancer clinic. Nevertheless, results of the few clinical trials that target integrins in cancer have thus far been disappointing. Importantly, these clinical failures likely reflect the emerging complexity of individual and combinatorial integrin function within both tumor cells and other cell types of the tumor microenvironment, together with a need to explore integrin-targeting agents not just as monotherapies but also as adjuvants to more conventional radiotherapies or chemotherapies. In this review, we will examine recent advances toward understanding how integrins regulate cancer progression, including their roles in intercellular communication and modulation of the tumor microenvironment. Additionally, we will discuss factors that underlie the limited efficacy of current efforts to target integrins in the cancer clinic as well as potential strategies to overcome these challenges.


2021 ◽  
Vol 12 ◽  
Author(s):  
Geng Lu ◽  
XinRui Jiang ◽  
Anni Wu ◽  
Jiawei Zhou ◽  
Hengjun Liu ◽  
...  

The rapid diagnosis of tuberculosis (TB) is of great significance for the control and treatment of TB. However, TB remains a major healthy, social, and economic burden worldwide because of the lack of ideal diagnostic biomarkers. Mycobacterium tuberculosis (M. tuberculosis)-encoded small RNA (sRNA) is a class of regulation small RNA. Several studies have identified M. tuberculosis encoded-sRNAs in the serum/plasm of M. tuberculosis-infected patients. Small extracellular vesicles are small membrane vesicles secreted by many cell types during physiological and pathological conditions. Recent evidence has indicated that most of the nucleic acids in the serum/plasma are packaged in the small extracellular vesicles and could serve as ideal diagnostic biomarkers. In this study, we attempted a novel approach for TB diagnosis: targeting small extracellular vesicles M. tuberculosis encoded sRNA (sRNA) by qRT-PCR. The results showed that M. tuberculosis-encoded ASdes and MTB-miR5 only existed in tuberculosis patients and have the potential to serve as a sensitive and accurate methodology for TB diagnosis.


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