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Frontiers in Immunology 2022Melanoma-derived extracellular vesicles (EVs) have been found to promote tumor growth and progression, and to predict patient responsiveness to immunotherapy.... (Review)
Review
Melanoma-derived extracellular vesicles (EVs) have been found to promote tumor growth and progression, and to predict patient responsiveness to immunotherapy. Consequently, EVs have been implicated in tumor immune evasion, and multiple studies reported immune-regulatory activities of melanoma EVs and . This review highlights mechanistic insights in EV-mediated regulation of various immune cell types, including effects on inflammatory, apoptotic, stress-sensing and immune checkpoint pathways as well as antigen-dependent responses. Additionally, current challenges in the field are discussed that need to be overcome to determine the clinical relevance of these various mechanisms and to develop corresponding therapeutic approaches to promote tumor immunity and immunotherapy responsiveness in melanoma patients in the future.
Topics: Antigens; Extracellular Vesicles; Humans; Immune Evasion; Immunotherapy; Melanoma
PubMed: 36081494
DOI: 10.3389/fimmu.2022.1002551 -
Trends in Molecular Medicine Aug 2022Extracellular vesicles (EVs) are actively shed into the circulation from both cancer and host cells. EVs are emerging as one of the diagnostic frontrunners for early... (Review)
Review
Extracellular vesicles (EVs) are actively shed into the circulation from both cancer and host cells. EVs are emerging as one of the diagnostic frontrunners for early cancer detection, disease monitoring, and treatment evaluation. The advantages of EVs rely on the fact that vesicles are being shed by dividing tumor cells, with indications that human and viral oncogenes, cellular metabolic rate, and tumor characteristics such as pH and hypoxia contribute to the high shed rates in cancer. In this review, we provide an overview of EVs and the rationale for using them for early cancer detection. We examine emerging technologies for single EV analysis (sEVA) and why these technologies will be necessary for early cancer detection.
Topics: Extracellular Vesicles; Humans; Neoplasms
PubMed: 35624008
DOI: 10.1016/j.molmed.2022.05.003 -
Neural Regeneration Research Feb 2024Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits. The currently available treatments involve surgical,... (Review)
Review
Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits. The currently available treatments involve surgical, medical, and rehabilitative strategies. However, none of these techniques can markedly reverse neurological deficits. Recently, extracellular vesicles from various cell sources have been applied to different models of spinal cord injury, thereby generating new cell-free therapies for the treatment of spinal cord injury. However, the use of extracellular vesicles alone is still associated with some notable shortcomings, such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons. Therefore, this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury, including the combination of extracellular vesicles with nanoparticles, exogenous drugs and/or biological scaffold materials, which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles. We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.
PubMed: 37488892
DOI: 10.4103/1673-5374.377413 -
Polymers Feb 2022Understanding and controlling vesicle shapes is fundamental challenge in biophysics and materials design. In this paper, we employ the Monte Carlo method to investigate...
Understanding and controlling vesicle shapes is fundamental challenge in biophysics and materials design. In this paper, we employ the Monte Carlo method to investigate the shape of soft vesicle induced by semiflexible polymer outside in two dimensions. The effect of bending stiffness κ of polymer and the strength εVP of attractive interaction between vesicle and polymer on the shape of vesicle is discussed in detail in the present paper. It is found that the shape of vesicle is influenced by κ and εVP. Typical shape of vesicles is observed, such as circular, cigar-like, double vesicle, and racquet-like. To engineer vesicle shape transformations is helpful for exploiting the richness of vesicle geometries for desired applications.
PubMed: 35215670
DOI: 10.3390/polym14040757 -
Frontiers in Endocrinology 2023The ovarian follicle consists of the oocyte, somatic cells, and follicular fluid (FF). Proper signalling between these compartments is required for optimal...
INTRODUCTION
The ovarian follicle consists of the oocyte, somatic cells, and follicular fluid (FF). Proper signalling between these compartments is required for optimal folliculogenesis. The association between polycystic ovarian syndrome (PCOS) and extracellular vesicular small non-coding RNAs (snRNAs) signatures in follicular fluid (FF) and how this relates to adiposity is unknown. The purpose of this study was to determine whether FF extracellular vesicle (FFEV)-derived snRNAs are differentially expressed (DE) between PCOS and non-PCOS subjects; and if these differences are vesicle-specific and/or adiposity-dependent.
METHODS
FF and granulosa cells (GC) were collected from 35 patients matched by demographic and stimulation parameters. FFEVs were isolated and snRNA libraries were constructed, sequenced, and analyzed.
RESULTS
miRNAs were the most abundant biotype present, with specific enrichment in exosomes (EX), whereas in GCs long non-coding RNAs were the most abundant biotype. In obese PCOS vs. lean PCOS, pathway analysis revealed target genes involved in cell survival and apoptosis, leukocyte differentiation and migration, JAK/STAT, and MAPK signalling. In obese PCOS FFEVs were selectively enriched (FFEVs vs. GCs) for miRNAs targeting p53 signalling, cell survival and apoptosis, FOXO, Hippo, TNF, and MAPK signalling.
DISCUSSION
We provide comprehensive profiling of snRNAs in FFEVs and GCs of PCOS and non-PCOS patients, highlighting the effect of adiposity on these findings. We hypothesize that the selective packaging and release of miRNAs specifically targeting anti-apoptotic genes into the FF may be an attempt by the follicle to reduce the apoptotic pressure of the GCs and stave off premature apoptosis of the follicle observed in PCOS.
Topics: Humans; Female; Follicular Fluid; Polycystic Ovary Syndrome; MicroRNAs; Obesity; Extracellular Vesicles
PubMed: 37404312
DOI: 10.3389/fendo.2023.1205385 -
Angewandte Chemie (International Ed. in... Dec 2019Targeted vesicle fusion is a promising approach to selectively control interactions between vesicle compartments and would enable the initiation of biological reactions... (Review)
Review
Targeted vesicle fusion is a promising approach to selectively control interactions between vesicle compartments and would enable the initiation of biological reactions in complex aqueous environments. Here, we explore how two features of vesicle membranes, DNA tethers and phase-segregated membranes, promote fusion between specific vesicle populations. Membrane phase-segregation provides an energetic driver for membrane fusion that increases the efficiency of DNA-mediated fusion events. The orthogonality provided by DNA tethers allows us to direct fusion and delivery of DNA cargo to specific vesicle populations. Vesicle fusion between DNA-tethered vesicles can be used to initiate in vitro protein expression to produce model soluble and membrane proteins. Engineering orthogonal fusion events between DNA-tethered vesicles provides a new strategy to control the spatiotemporal dynamics of cell-free reactions, expanding opportunities to engineer artificial cellular systems.
Topics: DNA; Humans
PubMed: 31596992
DOI: 10.1002/anie.201911544 -
Frontiers in Molecular Neuroscience 2022Interactions of lipid vesicles play important roles in a large variety of functions and dysfunctions in the human body. Vital for several biochemical functions is the...
Interactions of lipid vesicles play important roles in a large variety of functions and dysfunctions in the human body. Vital for several biochemical functions is the interaction between monomeric proteins and lipid membranes, and the induced phenomena such as fusion between vesicles and cell membranes, lipid exchange between the membranes, or vesicle fission. Identification of single events and their frequency of occurrence would provide valuable information about protein-lipid interactions in both healthy and degenerative pathways. In this work, we present a single-vesicle intensity and colocalization fluorescence microscopy assay with a custom-written MATLAB analysis program. The assay can be used to study lipid exchange as well as vesicle fusion and fission between two vesicle populations labeled with different fluorescent dyes. Vesicles from the two populations are first mixed and docked to a glass surface. The sample is then simultaneously imaged using two separate wavelength channels monitoring intensity changes and colocalization of vesicles from the two populations. The monomeric pre-synaptic protein α-synuclein (α-syn) and small unilamellar vesicles consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine, (DOPS), and monosialotetrahexosylganglioside (GM1) were used as a model system to evaluate the method. From our analysis, neither α-syn induced fusion nor lipid exchange was observed for vesicles consisting of DOPC:DOPS (7:3). However, including 10% GM1 in the vesicles resulted in a 91% increase of the number of vesicles within 10 min, combined with a 57% decrease in the average fluorescence intensity per vesicle, indicating that approximately half of the vesicles underwent fission. The method facilitates the study of lipid vesicle fusion, fission, and lipid exchange under controlled conditions. It also allows these events to be studied for systems with more complex composition including exosomes and lipid-based drug carriers, to enable a better understanding of their physicochemical properties.
PubMed: 36533132
DOI: 10.3389/fnmol.2022.1007699 -
Pharmaceutics May 2020Extracellular vesicles (EVs) are small membrane-based nanovesicles naturally released from cells. Extracellular vesicles mimetics (EVMs) are artificial vesicles... (Review)
Review
Extracellular vesicles (EVs) are small membrane-based nanovesicles naturally released from cells. Extracellular vesicles mimetics (EVMs) are artificial vesicles engineered from cells or in combination with lipid materials, and they mimic certain characteristics of EVs. As such, EVs facilitate intracellular communication by carrying and delivering biological materials, such as proteins, lipids, and nucleic acids, and they have been found to find organ tropism in preclinical studies. Because of their native structure and characteristics, they are considered promising drug carriers for future clinical use. This review outlines the origin and composition of natural EVs and EVM engineering and internalization. It then details different loading approaches, with examples of the drug delivery of therapeutic molecules. In addition, the advantages and disadvantages of loading drugs into EVs or EVMs as a drug delivery system are discussed. Finally, the advantages of EVMs over EVs and the future clinical translation of EVM-based drug delivery platforms are outlined.
PubMed: 32403320
DOI: 10.3390/pharmaceutics12050442 -
Aging Oct 2019
Topics: Caveolin 1; Extracellular Vesicles; Gene Expression Regulation; Humans; MicroRNAs
PubMed: 31652419
DOI: 10.18632/aging.102370 -
Aging Jul 2021
Topics: Aging; DNA, Mitochondrial; Extracellular Vesicles; Humans; Mitochondria
PubMed: 34289450
DOI: 10.18632/aging.203358