Extracellular vesicles and particles as mediators of long-range communication in cancer: connecting biological function to clinical applications

Extracellular Vesicles and Circulating Nucleic Acids, Journal Year: 2023, Volume and Issue: 4(3), P. 461 - 485

Published: Jan. 1, 2023

Over the past decade, extracellular vesicles and particles (EVPs) have emerged as critical mediators of intercellular communication, participating in numerous physiological pathological processes. In context cancer, EVPs exert local effects, such increased invasiveness, motility, reprogramming tumor stroma, well systemic including pre-metastatic niche formation, determining organotropism, promoting metastasis altering homeostasis various organs systems, liver, muscle, circulatory system. This review provides an overview advances EVP research during highlighting heterogeneity EVPs, their roles cancer progression, metastasis. Moreover, clinical potential useful biomarkers therapeutic agents is explored. Last but not least, progress analysis technologies that facilitated these discoveries discussed, which may further propel future.

Language: Английский

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Phosphatidylserine-exposing extracellular vesicles in body fluids are an innate defence against apoptotic mimicry viral pathogens

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(4), P. 905 - 921

Published: March 25, 2024

Abstract Some viruses are rarely transmitted orally or sexually despite their presence in saliva, breast milk, semen. We previously identified that extracellular vesicles (EVs) semen and saliva inhibit Zika virus infection. However, the antiviral spectrum underlying mechanism remained unclear. Here we applied lipidomics flow cytometry to show these EVs expose phosphatidylserine (PS). By blocking PS receptors, targeted by process of apoptotic mimicry, they interfere with viral attachment entry. Consequently, physiological concentrations vitro efficiently inhibited infection mimicry dengue, West Nile, Chikungunya, Ebola vesicular stomatitis viruses, but not severe acute respiratory syndrome coronavirus 2, human immunodeficiency 1, hepatitis C herpesviruses use other entry receptors. Our results identify role PS-rich body fluids innate defence against via mimicries, explaining why primarily PS-EV-deficient blood blood-ingesting arthropods rather than direct human-to-human contact.

Language: Английский

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Extracellular Vesicles as Mediators of Neuroinflammation in Intercellular and Inter-Organ Crosstalk

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7041 - 7041

Published: June 27, 2024

Neuroinflammation, crucial in neurological disorders like Alzheimer's disease, multiple sclerosis, and hepatic encephalopathy, involves complex immune responses. Extracellular vesicles (EVs) play a pivotal role intercellular inter-organ communication, influencing disease progression. EVs serve as key mediators the system, containing molecules capable of activating molecular pathways that exacerbate neuroinflammatory processes disorders. However, from mesenchymal stem cells show promise reducing neuroinflammation cognitive deficits. can cross CNS barriers, peripheral signals influence brain function via EV-mediated impacting barrier Understanding EV interactions within other organs could unveil novel therapeutic targets for

Language: Английский

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Comparison of EV characterization by commercial high‐sensitivity flow cytometers and a custom single‐molecule flow cytometer

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(8)

Published: Aug. 1, 2024

High-sensitivity flow cytometers have been developed for multi-parameter characterization of single extracellular vesicles (EVs), but performance varies among instruments and calibration methods. Here we compare the identical (split) EV samples derived from human colorectal cancer (DiFi) cells by three high-sensitivity cytometers, two commercial instruments, CytoFLEX/CellStream, a custom single-molecule cytometer (SMFC). DiFi EVs were stained with membrane dye di-8-ANEPPS PE-conjugated anti-EGFR or anti-tetraspanin (CD9/CD63/CD81) antibodies estimation size surface protein copy numbers. The limits detection (LODs) immunofluorescence vesicle based on using cross-calibrated, hard-dyed beads ∼10 PE/∼80 nm diameter CytoFLEX PEs/∼67 CellStream. For SMFC, LOD was 1 PE ≤ 35 size. population detected each system (di-8-ANEPPS

Language: Английский

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Novel insights into the isolation of extracellular vesicles by anion exchange chromatography

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 19, 2024

Extracellular vesicles (EVs) are membrane structures enclosed by a lipid bilayer that released into the extracellular space all types of cells. EVs involved in many physiological processes transporting biologically active substances. Interest for diagnostic biomarker research and therapeutic drug delivery applications has increased recent years. The realization full potential is currently hampered lack suitable technology isolation purification downstream pharmaceutical applications. Anion Exchange Chromatography (AEX) an established method which specific charges on AEX matrix can exploit surface their interactions to provide productive scalable separation method. using Eshmuno ® Q, strong tentacle anion exchange resin, was used demonstrate principal feasibility AEX-based gain insight isolated EV properties. Using several analysis techniques more detailed populations during isolation, we demonstrated although composition CD9/63/81 remained constant tetraspanin positive EVs, size distribution purity changed elution. Higher salt concentrations eluted larger negative vesicles.

Language: Английский

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Defining tropism and activity of natural and engineered extracellular vesicles

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 10, 2024

Extracellular vesicles (EVs) have important roles as mediators of cell-to-cell communication, with physiological functions demonstrated in various

Language: Английский

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Stabilizing milk-derived extracellular vesicles (mEVs) through lyophilization: a novel trehalose and tryptophan formulation for maintaining structure and Bioactivity during long-term storage

Journal of Biological Engineering, Journal Year: 2025, Volume and Issue: 19(1)

Published: Jan. 13, 2025

Abstract Extracellular vesicles (EVs) are widely investigated for their implications in cell-cell signaling, immune modulation, disease pathogenesis, cancer, regenerative medicine, and as a potential drug delivery vector. However, maintaining integrity bioactivity of EVs between Good Manufacturing Practice separation/filtration end-user application remains consistent bottleneck towards commercialization. Milk-derived extracellular (mEVs), separated from bovine milk, could provide relatively low-cost, scalable platform large-scale mEV production; however, the reliance on cold supply chain storage logistical financial burden biologics that unstable at room temperature. Herein, we aim to characterize engineer freeze-dried, formulation can be stored temperature without sacrificing structure/bioactivity reconstituted before delivery. In addition undertaking established assays structure function our preparations, introduce novel, efficient, high throughput assay based Electric Cell Substrate Impedance Sensing (ECIS) Human dermal fibroblast monolayers. By adding appropriate excipients, such trehalose tryptophan, describe protective preserves during long-term, storage. Our identification efficacy tryptophan novel additive lyophilization solutions represent significant advancement stabilizing small outside conditions.

Language: Английский

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Roles of extracellular vesicles from different origins in metabolic-associated fatty liver disease: progress and perspectives

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

Metabolic-Associated Fatty Liver Disease (MAFLD) is the most common chronic liver disease worldwide, associated with systemic metabolic dysregulation. It can progress from simple hepatic steatosis (MAFL) to more severe conditions like Steatohepatitis (MASH), fibrosis, cirrhosis, and Hepatocellular Carcinoma (HCC). There a critical lack of reliable non-invasive diagnostic methods effective pharmaceutical treatments for MAFLD/MASH, emphasizing need further research. Extracellular vesicles (EVs) are nanoscale structures that play important roles in cell signaling by delivering bioactive molecules. However, there significant gap literature regarding EVs hosts, plants, microbiota MAFLD. This review explores potential various sources—host, microbiota—as biomarkers, therapeutic agents, drug carriers, treatment targets Firstly, host-derived extracellular MAFLD, focus on cell-type specific their components—proteins, miRNAs, lipids—for diagnosis monitoring were discussed. Moreover, it highlighted mesenchymal stem (MSC)-derived reducing lipid accumulation injury, immune cell-derived mitigating inflammation fibrosis. The also discussed use as carriers due ability deliver molecules impact mechanisms. Additionally, summarized research plant-derived EVs, which help reduce accumulation, inflammation, enhance gut barrier function Also, explored microbial-derived novel targets, particularly relation insulin resistance, dysfunction Overall, exploring diverse host, plant, sources this offers valuable insights into biomarkers strategies, could pave way options increasingly prevalent disease. Notably, challenges translating clinical practice thoroughly discussed, aiming provide possible directions strategies future

Language: Английский

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Extracellular vesicles in atherothrombosis: From biomarkers and precision medicine to therapeutic targets

Immunological Reviews, Journal Year: 2022, Volume and Issue: 312(1), P. 6 - 19

Published: Aug. 22, 2022

Summary Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of global mortality. Extracellular vesicles (EVs) are small phospholipid that convey molecular bioactive cargoes and play essential roles in intercellular communication and, hence, a multifaceted role health disease. The present review offers glimpse into current state up‐to‐date concepts on EV field. It also covers their association with several risk factors ischemic conditions, being subclinical atherosclerosis utmost relevance for prevention. Interestingly, we show EVs hold promise as prognostic diagnostic well predictive markers ASCVD precision medicine era. We then report atherothrombosis, disentangling mechanisms involved initiation, progression, complication showing direct effect context arterial thrombosis. Finally, potential use therapeutic intervention is highlighted.

Language: Английский

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Scalable Generation of Nanovesicles from Human-Induced Pluripotent Stem Cells for Cardiac Repair

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 14334 - 14334

Published: Nov. 18, 2022

Extracellular vesicles (EVs) from stem cells have shown significant therapeutic potential to repair injured cardiac tissues and regulate pathological fibrosis. However, scalable generation of derived EVs for clinical utility remains a huge technical challenge. Here, we report rapid size-based extrusion strategy generate EV-like membranous nanovesicles (NVs) easily sourced human iPSCs in large quantities (yield 900× natural EVs). NVs isolated using density-gradient separation (buoyant density 1.13 g/mL) are spherical shape morphologically intact readily internalised by cardiomyocytes, primary fibroblasts, endothelial cells. captured the dynamic proteome parental include pluripotency markers (LIN28A, OCT4) regulators processes, including tissue (GJA1, HSP20/27/70, HMGB1), wound healing (FLNA, MYH9, ACTC1, ILK), stress response/translation initiation (eIF2S1/S2/S3/B4), hypoxia response (HMOX2, HSP90, GNB1), extracellular matrix organization (ITGA6, MFGE8, ITGB1). Functionally, significantly promoted tubule formation (angiogenesis) (p < 0.05) survival cardiomyocytes exposed low oxygen conditions (hypoxia) 0.0001), as well attenuated TGF-β mediated activation fibroblasts 0.0001). Quantitative profiling target cell following NV treatments revealed upregulation angiogenic proteins (MFGE8, MYH10, VDAC2) pro-survival (CNN2, THBS1, IGF2R) cardiomyocytes. In contrast, TGF-β-driven remodelling capacity (ACTN1, COL1A1/2/4A2/12A1, ITGA1/11, THBS1). This study presents approach generating functional repair.

Language: Английский

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