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Signal Transduction and Targeted Therapy Feb 2024Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers and... (Review)
Review
Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers and are ubiquitously released from cells under normal and pathological conditions. Human serum is a rich source of these EVs, though their isolation from serum proteins and non-EV lipid particles poses challenges. These vesicles transport various cellular components such as proteins, mRNAs, miRNAs, DNA, and lipids across distances, influencing numerous physiological and pathological events, including those within the tumor microenvironment (TME). Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents, drug delivery systems, and disease biomarkers. Especially in cancer diagnostics, EV detection can pave the way for early identification and offers potential as diagnostic biomarkers. Moreover, various EV subtypes are emerging as targeted drug delivery tools, highlighting their potential clinical significance. The need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains unfulfilled. Tapping into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the future. In this review, we discuss in detail the roles of EVs across various conditions, including cancers (encompassing head and neck, lung, gastric, breast, and hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune and renal diseases, emphasizing the potential advancements in molecular diagnostics and drug delivery.
Topics: Humans; Extracellular Vesicles; MicroRNAs; Biomarkers; Virus Diseases; Neoplasms; Tumor Microenvironment
PubMed: 38311623
DOI: 10.1038/s41392-024-01735-1 -
Journal of Extracellular Vesicles May 2021Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field....
Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.
Topics: Advisory Committees; Biomarkers; Body Fluids; Extracellular Vesicles; Humans; Kidney; Reference Standards; Reproducibility of Results; Societies; Urinary Tract; Urine
PubMed: 34035881
DOI: 10.1002/jev2.12093 -
Cell Reports. Medicine Sep 2023The bone microenvironment promotes cancer cell proliferation and dissemination. During periodic bone remodeling, osteoclasts undergo apoptosis, producing large numbers...
The bone microenvironment promotes cancer cell proliferation and dissemination. During periodic bone remodeling, osteoclasts undergo apoptosis, producing large numbers of apoptotic bodies (ABs). However, the biological role of osteoclast-derived ABs, which are residents of the bone-tumor niche, remains largely unknown. Here, we discover that AB-null MRL/lpr mice show resistance to breast cancer cell implantation, with more CD8 T cell infiltrations and a higher survival rate. We uncover that the membranous Siglec15 on osteoclast-derived ABs binds with sialylated Toll-like receptor 2 (TLR2) and blocks downstream co-stimulatory signaling, leading to the inhibition of naive CD8 T cell activation. In addition, our study shows that treatment with Siglec15 neutralizing antibodies significantly reduces the incidence of secondary metastases and improves the survival rate of mice with advanced breast cancer bone metastasis. Our findings reveal the immunosuppressive function of osteoclast-derived ABs in the bone-tumor niche and demonstrate the potential of Siglec15 as a common target for anti-resorption and immunotherapy.
Topics: Animals; Mice; CD8-Positive T-Lymphocytes; Extracellular Vesicles; Melanoma; Mice, Inbred MRL lpr; Osteoclasts; Tumor Microenvironment; Melanoma, Cutaneous Malignant
PubMed: 37607544
DOI: 10.1016/j.xcrm.2023.101165 -
International Journal of Molecular... Jun 2023Extracellular vesicles (EVs) are lipid bilayer-delimited particles. According to their size and synthesis pathway, EVs can be classified into exosomes, ectosomes... (Review)
Review
Extracellular vesicles (EVs) are lipid bilayer-delimited particles. According to their size and synthesis pathway, EVs can be classified into exosomes, ectosomes (microvesicles), and apoptotic bodies. Extracellular vesicles are of great interest to the scientific community due to their role in cell-to-cell communication and their drug-carrying abilities. The study aims to show opportunities for the application of EVs as drug transporters by considering techniques applicable for loading EVs, current limitations, and the uniqueness of this idea compared to other drug transporters. In addition, EVs have therapeutic potential in anticancer therapy (especially in glioblastoma, pancreatic cancer, and breast cancer).
Topics: Extracellular Vesicles; Exosomes; Cell-Derived Microparticles; Drug Delivery Systems
PubMed: 37373411
DOI: 10.3390/ijms241210267 -
Aging Oct 2019
Topics: Caveolin 1; Extracellular Vesicles; Gene Expression Regulation; Humans; MicroRNAs
PubMed: 31652419
DOI: 10.18632/aging.102370 -
Journal of Controlled Release :... Sep 2023Extracellular vesicles (EVs) are small membrane-bound vesicles released by cells. EVs are emerging as a promising class of therapeutic entity that could be adapted in... (Review)
Review
Extracellular vesicles (EVs) are small membrane-bound vesicles released by cells. EVs are emerging as a promising class of therapeutic entity that could be adapted in formulation due to their lack of immunogenicity and targeting capabilities. EVs have been shown to have similar regenerative and therapeutic effects to their parental cells and also have potential in disease diagnosis. To improve the therapeutic potential of EVs, researchers have developed various strategies for modifying them, including genetic engineering and chemical modifications which have been examined to confer target specificity and prevent rapid clearance after systematic injection. Formulation efforts have focused on utilising hydrogel and nano-formulation strategies to increase the persistence of EV localisation in a specific tissue or organ. Researchers have also used biomaterials or bioscaffolds to deliver EVs directly to disease sites and prolong EV release and exposure. This review provides an in-depth examination of the material design of EV delivery systems, highlighting the impact of the material properties on the molecular interactions and the maintenance of EV stability and function. The various characteristics of materials designed to regulate the stability, release rate and biodistribution of EVs are described. Other aspects of material design, including modification methods to improve the targeting of EVs, are also discussed. This review aims to offer an understanding of the strategies for designing EV delivery systems, and how they can be formulated to make the transition from laboratory research to clinical use.
Topics: Tissue Distribution; Extracellular Vesicles
PubMed: 37536545
DOI: 10.1016/j.jconrel.2023.07.059 -
Molecular Oncology Dec 2017Mammalian cells can release different types of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies. Accumulating evidence suggests that... (Review)
Review
Mammalian cells can release different types of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies. Accumulating evidence suggests that EVs play a role in cell-to-cell communication within the tumor microenvironment. EVs' components, such as proteins, noncoding RNAs [microRNAs (miRNAs), and long noncoding RNAs (lncRNAs)], messenger RNAs (mRNAs), DNA, and lipids, can mediate paracrine signaling in the tumor microenvironment. Recently, miRNAs encapsulated in secreted EVs have been identified in the extracellular space. Mature miRNAs that participate in intercellular communication are released from most cells, often within EVs, and disseminate through the extracellular fluid to reach remote target cells, including tumor cells, whose phenotypes they can influence by regulating mRNA and protein expression either as tumor suppressors or as oncogenes, depending on their targets. In this review, we discuss the roles of miRNAs in intercellular communication, the biological function of extracellular miRNAs, and their potential applications for diagnosis and therapeutics. We will give examples of miRNAs that behave as hormones.
Topics: Animals; Cell Communication; Exosomes; Extracellular Vesicles; Humans; MicroRNAs; Neoplasms; Paracrine Communication; Tumor Microenvironment
PubMed: 29024380
DOI: 10.1002/1878-0261.12144 -
Current Opinion in Plant Biology Oct 2022Extracellular vesicles (EVs) carrying RNA have attracted growing attention in plant cell biology. For a long time, EV release or uptake through the rigid plant cell wall... (Review)
Review
Extracellular vesicles (EVs) carrying RNA have attracted growing attention in plant cell biology. For a long time, EV release or uptake through the rigid plant cell wall was considered to be impossible and RNA outside cells to be unstable. Identified EV biomarkers have brought new insights into functional roles of EVs to transport their RNA cargo for systemic spread in plants and into plant-invading pathogens. RNA-binding proteins supposedly take over key functions in EV-mediated RNA secretion and transport, but the mechanisms of RNA sorting and EV translocation through the plant cell wall and plasma membrane are not understood. Characterizing the molecular players and the cellular mechanisms of plant RNA-containing EVs will create new knowledge in cell-to-cell and inter-organismal communication.
Topics: Biological Transport; Biomarkers; Cell Communication; Extracellular Vesicles; Plants; RNA, Plant
PubMed: 35964451
DOI: 10.1016/j.pbi.2022.102272 -
Cell Proliferation Jan 2021Metastasis refers to the progressive dissemination of primary tumour cells and their colonization of other tissues and is associated with most cancer-related... (Review)
Review
Metastasis refers to the progressive dissemination of primary tumour cells and their colonization of other tissues and is associated with most cancer-related mortalities. The disproportional and systematic distribution pattern of distant metastasis in different cancers has been well documented, as is termed metastatic organotropism, a process orchestrated by a combination of anatomical, pathophysiological, genetic and biochemical factors. Extracellular vesicles (EVs), nanosized cell-derived membrane-bound particles known to mediate intercellular communication, are now considered crucial in organ-specific metastasis. Here, we review and summarize recent findings regarding EV-associated organotropic metastasis as well as some of the general mechanisms by which EVs contribute to this important process in cancer and provide a future perspective on this emerging topic. We highlight studies that demonstrate a role of tumour-derived EVs in organotropic metastasis via pre-metastatic niche modulation. The bioactive cargo carried by EVs is of diagnostic and prognostic values, and counteracting the functions of such EVs may be a novel therapeutic strategy targeting metastasis. Further investigations are warranted to better understand the functions and mechanisms of EVs in organotropic metastasis and accelerate the relevant clinical translation.
Topics: Animals; Extracellular Vesicles; Humans; Neoplasm Metastasis; Neoplasms
PubMed: 33145869
DOI: 10.1111/cpr.12948 -
International Journal of Molecular... Jun 2023Extracellular vesicles (EVs) are cell-derived lipid vesicles in a size range of 20-1000 nm; often, these are classified as smaller and larger EVs in the literature or...
Extracellular vesicles (EVs) are cell-derived lipid vesicles in a size range of 20-1000 nm; often, these are classified as smaller and larger EVs in the literature or also commonly called small EVs ("exosomes") and medium/large EVs ("microvesicles") [...].
Topics: Phylogeny; Extracellular Vesicles; Exosomes; Cell-Derived Microparticles
PubMed: 37445643
DOI: 10.3390/ijms241310466