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Characterization of Extracellular Vesicles in Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 28 June 2024 | Viewed by 5396

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Department of Anesthesia and General Intensive Care, Clinical Department of Anesthesia, Medizinische Universität Wien, Vienna, Austria
Interests: cell biology of the lung and heart; organ protection; signaling transduction in the lung; experimental anesthesiology
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Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) are entities known to be released from all cell types, which contain signaling components such as proteins and nucleic acids enclosed by a lipid membrane. What was initially believed to be an unspecific secretion product has turned out to be a cell-type specific means of inter-cellular communication. The population of EVs is heterogenous with regard to the mode of biogenesis, size and cargo. Cargo signatures and their dependence on the (patho-)physiological status of the cell of origin as well as the mechanisms of specific detection of the recipient tissue are currently being investigated with the aim of defining EV-biomarkers and better understanding this communication route. In order to make progress in this field, analytical techniques are refined and frequently employ -omics technologies, such as proteomics and next-generation sequencing of RNAs.

This Special Issue invites contributions from this exciting research field with a special emphasis on the molecular characterization of extracellular vesicles depending on the physiological state of the secreting cell type and the recipient tissues.

Dr. Verena Tretter
Guest Editor

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Keywords

  • extracellular vesicle
  • exosomes
  • microvesicles
  • vesicle cargo

Published Papers (3 papers)

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22 pages, 4073 KiB  
Article
The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma
by Wolfgang Schaubmayr, Beatrix Hochreiter, Eva Hunyadi-Gulyas, Louise Riegler, Katy Schmidt, Akos Tiboldi, Bernhard Moser, Klaus U. Klein, Katharina Krenn, Gisela Scharbert, Thomas Mohr, Johannes A. Schmid, Andreas Spittler and Verena Tretter
Int. J. Mol. Sci. 2024, 25(4), 2415; https://doi.org/10.3390/ijms25042415 - 19 Feb 2024
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Abstract
The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize [...] Read more.
The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia. Full article
(This article belongs to the Special Issue Characterization of Extracellular Vesicles in Disease)
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Review

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12 pages, 1257 KiB  
Review
Acute Kidney Injury by Ischemia/Reperfusion and Extracellular Vesicles
by Mikkel Ørnfeldt Nørgård and Per Svenningsen
Int. J. Mol. Sci. 2023, 24(20), 15312; https://doi.org/10.3390/ijms242015312 - 18 Oct 2023
Cited by 1 | Viewed by 2001
Abstract
Acute kidney injury (AKI) is often caused by ischemia-reperfusion injury (IRI). IRI significantly affects kidney metabolism, which elicits pro-inflammatory responses and kidney injury. The ischemia/reperfusion of the kidney is associated with transient high mitochondrial-derived reactive oxygen species (ROS) production rates. Excessive mitochondrial-derived ROS [...] Read more.
Acute kidney injury (AKI) is often caused by ischemia-reperfusion injury (IRI). IRI significantly affects kidney metabolism, which elicits pro-inflammatory responses and kidney injury. The ischemia/reperfusion of the kidney is associated with transient high mitochondrial-derived reactive oxygen species (ROS) production rates. Excessive mitochondrial-derived ROS damages cellular components and, together with other pathogenic mechanisms, elicits a range of acute injury mechanisms that impair kidney function. Mitochondrial-derived ROS production also stimulates epithelial cell secretion of extracellular vesicles (EVs) containing RNAs, lipids, and proteins, suggesting that EVs are involved in AKI pathogenesis. This literature review focuses on how EV secretion is stimulated during ischemia/reperfusion and how cell-specific EVs and their molecular cargo may modify the IRI process. Moreover, critical pitfalls in the analysis of kidney epithelial-derived EVs are described. In particular, we will focus on how the release of kidney epithelial EVs is affected during tissue analyses and how this may confound data on cell-to-cell signaling. By increasing awareness of methodological pitfalls in renal EV research, the risk of false negatives can be mitigated. This will improve future EV data interpretation regarding EVs contribution to AKI pathogenesis and their potential as biomarkers or treatments for AKI. Full article
(This article belongs to the Special Issue Characterization of Extracellular Vesicles in Disease)
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18 pages, 358 KiB  
Review
Engineered Extracellular Vesicles: Emerging Therapeutic Strategies for Translational Applications
by Jessica N. Ziegler and Changhai Tian
Int. J. Mol. Sci. 2023, 24(20), 15206; https://doi.org/10.3390/ijms242015206 - 15 Oct 2023
Viewed by 1758
Abstract
Extracellular vesicles (EVs) are small, membrane-bound vesicles used by cells to deliver biological cargo such as proteins, mRNA, and other biomolecules from one cell to another, thus inducing a specific response in the target cell and are a powerful method of cell to [...] Read more.
Extracellular vesicles (EVs) are small, membrane-bound vesicles used by cells to deliver biological cargo such as proteins, mRNA, and other biomolecules from one cell to another, thus inducing a specific response in the target cell and are a powerful method of cell to cell and organ to organ communication, especially during the pathogenesis of human disease. Thus, EVs may be utilized as prognostic and diagnostic biomarkers, but they also hold therapeutic potential just as mesenchymal stem cells have been used in therapeutics. However, unmodified EVs exhibit poor targeting efficacy, leading to the necessity of engineered EVS. To highlight the advantages and therapeutic promises of engineered EVs, in this review, we summarized the research progress on engineered EVs in the past ten years, especially in the past five years, and highlighted their potential applications in therapeutic development for human diseases. Compared to the existing stem cell-derived EV-based therapeutic strategies, engineered EVs show greater promise in clinical applications: First, engineered EVs mediate good targeting efficacy by exhibiting a targeting peptide that allows them to specifically target a specific organ or even cell type, thus avoiding accumulation in undesired locations and increasing the potency of the treatment. Second, engineered EVs can be artificially pre-loaded with any necessary biomolecular cargo or even therapeutic drugs to treat a variety of human diseases such as cancers, neurological diseases, and cardiovascular ailments. Further research is necessary to improve logistical challenges in large-scale engineered EV manufacturing, but current developments in engineered EVs prove promising to greatly improve therapeutic treatment for traditionally difficult to treat diseases. Full article
(This article belongs to the Special Issue Characterization of Extracellular Vesicles in Disease)
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