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Theranostics 2018Exosomes are common membrane-bound nanovesicles that contain diverse biomolecules, such as lipids, proteins, and nucleic acids. Exosomes are derived from cells through... (Review)
Review
Exosomes are common membrane-bound nanovesicles that contain diverse biomolecules, such as lipids, proteins, and nucleic acids. Exosomes are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Exosome secretion is a constitutive phenomenon that is involved in both physiological and pathological processes and determines both the exosomal surface molecules and the contents. Hence, we can exploit exosomes as biomarkers, vaccines and drug carriers and modify them rationally for therapeutic interventions. However, it is still a challenge to identify, isolate and quantify exosomes accurately, efficiently and selectively. Further studies on exosomes will explore their potential in translational medicine and provide new avenues for the creation of effective clinical diagnostics and therapeutic strategies; the use of exosomes in these applications can be called exosome theranostics. This review describes the fundamental processes of exosome formation and uptake. In addition, the physiological and pathological roles of exosomes in biology are also illustrated with a focus on how exosomes can be exploited or engineered as powerful tools in translational medicine.
Topics: Animals; Biomarkers; Exosomes; Extracellular Vesicles; Humans; Theranostic Nanomedicine; Translational Research, Biomedical
PubMed: 29290805
DOI: 10.7150/thno.21945 -
Biotechnology Advances Oct 2022In recent years, extracellular vesicles (EVs), specifically exosomes, have emerged as a promising strategy for treating a wide spectrum of pathologies, such as cancer... (Review)
Review
In recent years, extracellular vesicles (EVs), specifically exosomes, have emerged as a promising strategy for treating a wide spectrum of pathologies, such as cancer and COVID-19, as well as promoting tissue regeneration in various conditions, including cardiomyopathies and spinal cord injuries. Despite the great potential of EV-based therapies, poor yield and unscalable production of EVs remain big challenges to overcome to translate these types of treatment to clinical practices. Here, we review different strategies for enhancing EV yield by physical, biological or chemical means. Some of these novel approaches can lead to about 100-fold increase in EV production yield, thus bringing closer the clinical translation with regard to scalability and efficiency.
Topics: COVID-19; Exosomes; Extracellular Vesicles; Humans; Neoplasms
PubMed: 35588952
DOI: 10.1016/j.biotechadv.2022.107983 -
Nature Jan 2022Exosomes and other small extracellular vesicles (sEVs) provide a unique mode of cell-to-cell communication in which microRNAs (miRNAs) produced and released from one...
Exosomes and other small extracellular vesicles (sEVs) provide a unique mode of cell-to-cell communication in which microRNAs (miRNAs) produced and released from one cell are taken up by cells at a distance where they can enact changes in gene expression. However, the mechanism by which miRNAs are sorted into exosomes/sEVs or retained in cells remains largely unknown. Here we demonstrate that miRNAs possess sorting sequences that determine their secretion in sEVs (EXOmotifs) or cellular retention (CELLmotifs) and that different cell types, including white and brown adipocytes, endothelium, liver and muscle, make preferential use of specific sorting sequences, thus defining the sEV miRNA profile of that cell type. Insertion or deletion of these CELLmotifs or EXOmotifs in a miRNA increases or decreases retention in the cell of production or secretion into exosomes/sEVs. Two RNA-binding proteins, Alyref and Fus, are involved in the export of miRNAs carrying one of the strongest EXOmotifs, CGGGAG. Increased miRNA delivery mediated by EXOmotifs leads to enhanced inhibition of target genes in distant cells. Thus, this miRNA code not only provides important insights that link circulating exosomal miRNAs to tissues of origin, but also provides an approach for improved targeting in RNA-mediated therapies.
Topics: Adipocytes; Cell Communication; Endothelium; Exosomes; Extracellular Vesicles; Liver; MicroRNAs; Muscles
PubMed: 34937935
DOI: 10.1038/s41586-021-04234-3 -
Cellular and Molecular Neurobiology Apr 2016Extracellular vesicles are a heterogeneous group of membrane-limited vesicles loaded with various proteins, lipids, and nucleic acids. Release of extracellular vesicles... (Review)
Review
Extracellular vesicles are a heterogeneous group of membrane-limited vesicles loaded with various proteins, lipids, and nucleic acids. Release of extracellular vesicles from its cell of origin occurs either through the outward budding of the plasma membrane or through the inward budding of the endosomal membrane, resulting in the formation of multivesicular bodies, which release vesicles upon fusion with the plasma membrane. The release of vesicles can facilitate intercellular communication by contact with or by internalization of contents, either by fusion with the plasma membrane or by endocytosis into "recipient" cells. Although the interest in extracellular vesicle research is increasing, there are still no real standards in place to separate or classify the different types of vesicles. This review provides an introduction into this expanding and complex field of research focusing on the biogenesis, nucleic acid cargo loading, content, release, and uptake of extracellular vesicles.
Topics: Animals; Biological Transport; Exosomes; Extracellular Vesicles; Humans; Models, Biological; RNA
PubMed: 27053351
DOI: 10.1007/s10571-016-0366-z -
Nature Reviews. Immunology Apr 2023The twenty-first century has witnessed major developments in the field of extracellular vesicle (EV) research, including significant steps towards defining standard... (Review)
Review
The twenty-first century has witnessed major developments in the field of extracellular vesicle (EV) research, including significant steps towards defining standard criteria for the separation and detection of EVs. The recent recognition that EVs have the potential to function as biomarkers or as therapeutic tools has attracted even greater attention to their study. With this progress in mind, an updated comprehensive overview of the roles of EVs in the immune system is timely. This Review summarizes the roles of EVs in basic processes of innate and adaptive immunity, including inflammation, antigen presentation, and the development and activation of B cells and T cells. It also highlights key progress related to deciphering the roles of EVs in antimicrobial defence and in allergic, autoimmune and antitumour immune responses. It ends with a focus on the relevance of EVs to immunotherapy and vaccination, drawing attention to ongoing or recently completed clinical trials that aim to harness the therapeutic potential of EVs.
Topics: Humans; Extracellular Vesicles; Immune System; Biomarkers; Adaptive Immunity; Inflammation
PubMed: 35927511
DOI: 10.1038/s41577-022-00763-8 -
Nature Reviews. Molecular Cell Biology Jul 2023To coordinate, adapt and respond to biological signals, cells convey specific messages to other cells. An important aspect of cell-cell communication involves secretion... (Review)
Review
To coordinate, adapt and respond to biological signals, cells convey specific messages to other cells. An important aspect of cell-cell communication involves secretion of molecules into the extracellular space. How these molecules are selected for secretion has been a fundamental question in the membrane trafficking field for decades. Recently, extracellular vesicles (EVs) have been recognized as key players in intercellular communication, carrying not only membrane proteins and lipids but also RNAs, cytosolic proteins and other signalling molecules to recipient cells. To communicate the right message, it is essential to sort cargoes into EVs in a regulated and context-specific manner. In recent years, a wealth of lipidomic, proteomic and RNA sequencing studies have revealed that EV cargo composition differs depending upon the donor cell type, metabolic cues and disease states. Analyses of distinct cargo 'fingerprints' have uncovered mechanistic linkages between the activation of specific molecular pathways and cargo sorting. In addition, cell biology studies are beginning to reveal novel biogenesis mechanisms regulated by cellular context. Here, we review context-specific mechanisms of EV biogenesis and cargo sorting, focusing on how cell signalling and cell state influence which cellular components are ultimately targeted to EVs.
Topics: Proteomics; Biological Transport; Extracellular Vesicles; Protein Transport; Signal Transduction; Cell Communication
PubMed: 36765164
DOI: 10.1038/s41580-023-00576-0 -
The Journal of Clinical Investigation Apr 2016Two broad categories of extracellular vesicles (EVs), exosomes and shed microvesicles (sMVs), which differ in size distribution as well as protein and RNA profiles, have... (Review)
Review
Two broad categories of extracellular vesicles (EVs), exosomes and shed microvesicles (sMVs), which differ in size distribution as well as protein and RNA profiles, have been described. EVs are known to play key roles in cell-cell communication, acting proximally as well as systemically. This Review discusses the nature of EV subtypes, strategies for isolating EVs from both cell-culture media and body fluids, and procedures for quantifying EVs. We also discuss proteins selectively enriched in exosomes and sMVs that have the potential for use as markers to discriminate between EV subtypes, as well as various applications of EVs in clinical diagnosis.
Topics: Animals; Biomarkers; Body Fluids; Cell-Derived Microparticles; Culture Media; Exosomes; Humans
PubMed: 27035807
DOI: 10.1172/JCI81129 -
Infection and Immunity Nov 2020Extracellular vesicles (EVs) are membrane-derived lipid bilayers secreted by bacteria and eukaryotic cells. Bacterial membrane vesicles were discovered over 60 years... (Review)
Review
Extracellular vesicles (EVs) are membrane-derived lipid bilayers secreted by bacteria and eukaryotic cells. Bacterial membrane vesicles were discovered over 60 years ago and have been extensively studied in Gram-negative bacteria. During their production, EVs are loaded with proteins, nucleic acids, and various compounds that are subsequently released into the environment. Depending on the packaged cargo, EVs have a broad spectrum of action and are involved in pathogenesis, antibiotic resistance, nutrient uptake, and nucleic acid transfer. Due to differences in cell wall structure, EVs in Gram-positive bacteria have been disregarded for decades, and our understanding of their biogenesis and host cell interaction is incomplete. Recently, studies on bacteria such as , spp., , and spp. have demonstrated EV production in Gram-positive bacteria and shown the great importance EVs have in Gram-positive bacterial physiology and disease progression. Here, we review the latest findings on the biogenesis and functions of EVs from Gram-positive bacteria and identify key areas for future research.
Topics: Animals; Bacillus subtilis; Bioengineering; Biological Transport; Extracellular Vesicles; Gram-Positive Bacteria; Humans; Inflammation; Mycobacterium; Staphylococcal Infections; Staphylococcus aureus; Streptococcus; Vaccines
PubMed: 32989035
DOI: 10.1128/IAI.00433-20 -
Journal of Hematology & Oncology Sep 2021Extracellular vesicles (EVs) are cell-derived membrane structures enclosing proteins, lipids, RNAs, metabolites, growth factors, and cytokines. EVs have emerged as... (Review)
Review
Extracellular vesicles (EVs) are cell-derived membrane structures enclosing proteins, lipids, RNAs, metabolites, growth factors, and cytokines. EVs have emerged as essential intercellular communication regulators in multiple physiological and pathological processes. Previous studies revealed that mesenchymal stem cells (MSCs) could either support or suppress tumor progression in different cancers by paracrine signaling via MSC-derived EVs. Evidence suggested that MSC-derived EVs could mimic their parental cells, possessing pro-tumor and anti-tumor effects, and inherent tumor tropism. Therefore, MSC-derived EVs can be a cell-free cancer treatment alternative. This review discusses different insights regarding MSC-derived EVs' roles in cancer treatment and summarizes bioengineered MSC-derived EVs' applications as safe and versatile anti-tumor agent delivery platforms. Meanwhile, current hurdles of moving MSC-derived EVs from bench to bedside are also discussed.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Proliferation; Drug Delivery Systems; Extracellular Vesicles; Humans; Mesenchymal Stem Cells; Neoplasms
PubMed: 34479611
DOI: 10.1186/s13045-021-01141-y -
Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications.Pharmacology & Therapeutics May 2022Extracellular vesicles (EVs), including exosomes and microvesicles, are lipid bilayer particles naturally released from the cell. While exosomes are formed as... (Review)
Review
Extracellular vesicles (EVs), including exosomes and microvesicles, are lipid bilayer particles naturally released from the cell. While exosomes are formed as intraluminal vesicles (ILVs) of the multivesicular endosomes (MVEs) and released to extracellular space upon MVE-plasma membrane fusion, microvesicles are generated through direct outward budding of the plasma membrane. Exosomes and microvesicles have same membrane orientation, different yet overlapping sizes; their cargo contents are selectively packed and dependent on the source cell type and functional state. Both exosomes and microvesicles can transfer bioactive RNAs, proteins, lipids, and metabolites from donor to recipient cells and influence the biological properties of the latter. Over the last decade, their potential roles as effective inter-tissue communicators in cardiovascular physiology and pathology have been increasingly appreciated. In addition, EVs are attractive sources of biomarkers for the diagnosis and prognosis of diseases, because they acquire their complex cargoes through cellular processes intimately linked to disease pathogenesis. Furthermore, EVs obtained from various stem/progenitor cell populations have been tested as cell-free therapy in various preclinical models of cardiovascular diseases and demonstrate unequivocally encouraging benefits. Here we summarize the findings from recent research on the biological functions of EVs in the ischemic heart disease and heart failure, and their potential as novel diagnostic biomarkers and therapeutic opportunities.
Topics: Biomarkers; Cardiovascular Diseases; Cell Communication; Cell-Derived Microparticles; Exosomes; Extracellular Vesicles; Humans
PubMed: 34687770
DOI: 10.1016/j.pharmthera.2021.108025