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The Molecular Basis of Extracellular Vesicles in Health and Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 8228

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Special Issue Editor

Dr. Taral R. Lunavat

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Guest Editor

1. Department of Neurology, Molecular Neurogenetics Unit-West, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
2. Department of Biomedicine, University of Bergen, Bergen, Norway
Interests: extracellular vesicles; neuro-oncology; tumor immunology; tumor microenvironment; microRNAs; gene and cell therapy

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs), i.e., nanoparticles with a bilayer membrane, are secreted by almost all cell types and can be found in body fluids. EVs are heterogeneous and play a crucial role in cell-to-cell communication by carrying bioactive molecules that can modulate the behavior of target cells at both close and distant sites. The composition of EVs is determined by their biogenetic molecular pathway and the microenvironment of the parent cell. Regardless of their origin, EVs carry a diverse set of bioactive molecules, including lipids, nucleic acids, and proteins, either inside the vesicle or exposed on their surface. Recent studies have provided valuable insight into the physiological and pathological roles of EVs. Technological advances in the detection, isolation, and characterization of EVs are significantly expanding and supporting research on their potential in the diagnosis and therapy of various diseases, such as cancer, cardiovascular disease, autoimmune disorders, neurological diseases, and infectious diseases.

This Special Issue aims to provide comprehensive and critical knowledge on the pre-clinical and clinical applications of EVs in relation to the pathophysiology of different diseases, evaluate their diagnostic and therapeutic potential, and review the progress in this field. The published research articles will also provide new insights into the genetic and epigenetic predictors driven by EVs involved in the etiology of multiple diseases.

Scope and information for Authors:

This Special Issue covers various areas of research on the involvement of EVs in diseases, including genetics, epigenetics, RNAs, proteomics, metabolomics, and microbiome studies. The scope ranges from the most basic to the most clinically applied, incorporating methodology, applications, and implications. We welcome submissions of research articles on the following sub-themes: extracellular vesicles and circulating nucleic acids, extracellular vesicles for the transport of genetic information and gene therapy, the transfer of nucleic acid to mediate communication by extracellular vesicles, the role of extracellular vesicles in epigenetics, microbiota-derived extracellular vesicles and their molecular cargo, extracellular vesicles as biomarkers and therapeutic targets, the heterogeneity of EVs in diseases, and new technology to isolate and characterize EVs.

The Special Issue is open access and both reviews and original research articles are welcome for submissions.

Dr. Taral R. Lunavat
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

exosomes
microvesicles
extracellular vesicles
genetic material
therapeutics
diagnostics
biomarkers
molecular pathway
liquid biopsy
metabolism
omics

Published Papers (6 papers)

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Research

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18 pages, 3463 KiB

Open AccessArticle

Rapid Biodistribution of Fluorescent Outer-Membrane Vesicles from the Intestine to Distant Organs via the Blood in Mice

by Béatrice Schaack, Corinne Mercier, Maya Katby, Dalil Hannani, Julien Vollaire, Julie Suzanne Robert, Clément Caffaratti, Françoise Blanquet, Olivier Nicoud, Véronique Josserand and David Laurin

Int. J. Mol. Sci. 2024, 25(3), 1821; https://doi.org/10.3390/ijms25031821 - 02 Feb 2024

Viewed by 974

Abstract

A cell’s ability to secrete extracellular vesicles (EVs) for communication is present in all three domains of life. Notably, Gram-negative bacteria produce a specific type of EVs called outer membrane vesicles (OMVs). We previously observed the presence of OMVs in human blood, which could represent a means of communication from the microbiota to the host. Here, in order to investigate the possible translocation of OMVs from the intestine to other organs, the mouse was used as an animal model after OMVs administration. To achieve this, we first optimized the signal of OMVs containing the fluorescent protein miRFP713 associated with the outer membrane anchoring peptide OmpA by adding biliverdin, a fluorescence cofactor, to the cultures. The miRFP713-expressing OMVs produced in E. coli REL606 strain were then characterized according to their diameter and protein composition. Native- and miRFP713-expressing OMVs were found to produce homogenous populations of vesicles. Finally, in vivo and ex vivo fluorescence imaging was used to monitor the distribution of miRFP713-OMVs in mice in various organs whether by intravenous injection or oral gavage. The relative stability of the fluorescence signals up to 3 days post-injection/gavage paves the way to future studies investigating the OMV-based communication established between the different microbiotas and their host. Full article

(This article belongs to the Special Issue The Molecular Basis of Extracellular Vesicles in Health and Diseases)

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12 pages, 4544 KiB

Open AccessArticle

Human Umbilical Cord Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Reduce Skin Inflammation In Vitro

by Tzou-Yien Lin, Tsong-Min Chang, Wei-Cheng Tsai, Yi-Ju Hsieh, Li-Ting Wang and Huey-Chun Huang

Int. J. Mol. Sci. 2023, 24(23), 17109; https://doi.org/10.3390/ijms242317109 - 04 Dec 2023

Cited by 1 | Viewed by 1255

Abstract

The protective roles of extracellular vesicles derived from human umbilical cord mesenchymal stem cells against oxazolone-induced damage in the immortalized human keratinocyte cell line HaCaT were investigated. The cells were pretreated with or without UCMSC-derived extracellular vesicles 24 h before oxazolone exposure. The pretreated UVMSC-EVs showed protective activity, elevating cell viability, reducing intracellular ROS, and reducing the changes in the mitochondrial membrane potential compared to the cells with a direct oxazolone treatment alone. The UCMSC-EVs exhibited anti-inflammatory activity via reducing the inflammatory cytokines IL-1β and TNF-α. A mechanism study showed that the UCMSC-EVs increased the protein expression levels of SIRT1 and P53 and reduced P65 protein expression. It was concluded that UVMSC-EVs can induce the antioxidant defense systems of HaCaT cells and that they may have potential as functional ingredients in anti-aging cosmetics for skin care. Full article

(This article belongs to the Special Issue The Molecular Basis of Extracellular Vesicles in Health and Diseases)

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16 pages, 2683 KiB

Open AccessArticle

RNA Profiles of Tear Fluid Extracellular Vesicles in Patients with Dry Eye-Related Symptoms

by Tanya Cross, Reidun Øvstebø, Berit Sletbakk Brusletto, Anne-Marie Siebke Trøseid, Ole Kristoffer Olstad, Trude Aspelin, Catherine Joan Jackson, Xiangjun Chen, Tor Paaske Utheim and Kari Bente Foss Haug

Int. J. Mol. Sci. 2023, 24(20), 15390; https://doi.org/10.3390/ijms242015390 - 20 Oct 2023

Viewed by 1594

Abstract

Currently, diagnosing and stratifying dry eye disease (DED) require multiple tests, motivating interest in a single definitive test. The purpose of this study was to investigate the potential for using tear fluid extracellular vesicle (EV)-RNA in DED diagnostics. With a role in intercellular communication, nanosized EVs facilitate the protected transport of diverse bioactive molecules in biofluids, including tears. Schirmer strips were used to collect tears from 10 patients presenting with dry eye-related symptoms at the Norwegian Dry Eye Clinic. The samples comprised two groups, five from patients with a tear film break-up time (TBUT) of 2 s and five from patients with a TBUT of 10 s. Tear fluid EV-RNA was isolated using a Qiagen exoRNeasy Midi Kit, and the RNA was characterized using Affymetrix Clariom^TM D microarrays. The mean signal values of the two groups were compared using a one-way ANOVA. A total of 26,639 different RNA transcripts were identified, comprising both mRNA and ncRNA subtypes. Approximately 6% of transcripts showed statistically significant differential abundance between the two groups. The mRNA sodium channel modifier 1 (SCNM1) was detected at a level 3.8 times lower, and the immature microRNA-130b was detected at a level 1.5 times higher in the group with TBUT 2 s compared to the group with TBUT 10 s. This study demonstrates the potential for using tear fluid EV-RNA in DED diagnostics. Full article

(This article belongs to the Special Issue The Molecular Basis of Extracellular Vesicles in Health and Diseases)

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22 pages, 4670 KiB

Open AccessArticle

Exosomes Derived from Hypoxia-Cultured Human Adipose Stem Cells Alleviate Articular Chondrocyte Inflammaging and Post-Traumatic Osteoarthritis Progression

by Ling-Hua Chang, Shun-Cheng Wu, Chung-Hwan Chen, Jhen-Wei Chen, Wan-Chun Huang, Che-Wei Wu, Yi-Shan Lin, Yu-Ju Chen, Je-Ken Chang and Mei-Ling Ho

Int. J. Mol. Sci. 2023, 24(17), 13414; https://doi.org/10.3390/ijms241713414 - 29 Aug 2023

Cited by 8 | Viewed by 1995

Abstract

Osteoarthritis (OA) is the most common age-related degenerative joint disease. Inflammaging, linking inflammation and aging, is found in senescent cells with the secretions of matrix-degrading proteins and proinflammatory cytokines. The senescence-associated secretory phenotype (SASP) plays a very important role in OA progression. However, there remains no effective way to suppress OA progression, especially by suppressing inflammaging and/or the chondrocyte SASP. Recent studies have shown that exosomes derived from hypoxia-cultured BMSCs can regenerate cartilage in OA animal models. Some reports have further indicated that exosomes secreted from MSCs contribute to the efficacy of MSC therapy in OA. However, whether hypoxia-cultured ADSC-secreted exosomes (hypoxia-ADSC-Exos) can alleviate the chondrocyte SASP or OA progression remains unclear. Accordingly, we hypothesized that hypoxia-ADSC-Exos have a beneficial effect on the normal functions of human articular chondrocytes (HACs), can attenuate the SASP of OA-like HACs in vitro, and further suppress OA progression in rats. Hypoxia-ADSC-Exos were derived from ADSCs cultured in 1% O₂ and 10% de-Exo-FBS for 48 h. The molecular and cell biological effects of hypoxia-ADSC-Exos were tested on IL1-β-induced HACs as OA-like HACs in vitro, and the efficacy of OA treatment was tested in ACLT-induced OA rats. The results showed that hypoxia-ADSC-Exos had the best effect on GAG formation in normal HACs rather than those cultured in normoxia or hypoxia plus 2% de-Exo-FBS. We further found that hypoxia-ADSC-Exos alleviated the harmful effect in OA-like HACs by decreasing markers of normal cartilage (GAG and type II collagen) and increasing markers of fibrous or degenerative cartilage (type I or X collagen), matrix degradation enzymes (MMP13 and ADAMT5), and inflammatory cytokines (TNFα and IL-6). More importantly, intra-articular treatment with hypoxia-ADSC-Exos suppressed OA progression, as evidenced by the weight-bearing function test and cartilage GAG quantification in ACLT rats. Moreover, through NGS and bioinformatic analysis, seven potential miRNAs were found in hypoxia-ADSC-Exos, which may contribute to regulating cellular oxidative stress and attenuating cell senescence. In summary, we demonstrated that hypoxia-ADSC-Exos, carrying potent miRNAs, not only improve normal HAC function but also alleviate HAC inflammaging and OA progression. The results suggest that hypoxia-ADSC-Exo treatment may offer another strategy for future OA therapy. Full article

(This article belongs to the Special Issue The Molecular Basis of Extracellular Vesicles in Health and Diseases)

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Review

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20 pages, 995 KiB

Open AccessReview

The Role of Extracellular Vesicles in Allergic Sensitization: A Systematic Review

by Davis Tucis, Georgina Hopkins, William Browne, Victoria James, David Onion and Lucy C. Fairclough

Int. J. Mol. Sci. 2024, 25(8), 4492; https://doi.org/10.3390/ijms25084492 - 19 Apr 2024

Viewed by 348

Abstract

Allergies affect approximately 10–30% of people worldwide, with an increasing number of cases each year; however, the underlying mechanisms are still poorly understood. In recent years, extracellular vesicles (EVs) have been suggested to play a role in allergic sensitization and skew to a T helper type 2 (Th2) response. The aim of this review is to highlight the existing evidence of EV involvement in allergies. A total of 22 studies were reviewed; 12 studies showed EVs can influence a Th2 response, while 10 studies found EVs promoted a Th1 or Treg response. EVs can drive allergic sensitization through up-regulation of pro-Th2 cytokines, such as IL-4 and IL-13. In addition, EVs from MRSA can induce IgE hypersensitivity in mice towards MRSA. On the other hand, EVs can induce tolerance in the immune system; for example, pre-exposing OVA-loaded EVs prevented OVA sensitization in mice. The current literature thus suggests that EVs play an essential role in allergy. Further research utilizing human in vitro models and clinical studies is needed to give a reliable account of the role of EVs in allergy. Full article

(This article belongs to the Special Issue The Molecular Basis of Extracellular Vesicles in Health and Diseases)

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25 pages, 1831 KiB

Open AccessReview

The Regulation of Exosome Generation and Function in Physiological and Pathological Processes

by Ying Wang, Tong Xiao, Chaoran Zhao and Guiying Li

Int. J. Mol. Sci. 2024, 25(1), 255; https://doi.org/10.3390/ijms25010255 - 23 Dec 2023

Cited by 2 | Viewed by 1227

Abstract

Exosomes, a type of extracellular vesicle with a diameter of approximately 100 nm that is secreted by all cells, regulate the phenotype and function of recipient cells by carrying molecules such as proteins, nucleic acids, and lipids and are important mediators of intercellular communication. Exosomes are involved in various physiological and pathological processes such as immunomodulation, angiogenesis, tumorigenesis, metastasis, and chemoresistance. Due to their excellent properties, exosomes have shown their potential application in the clinical diagnosis and treatment of disease. The functions of exosomes depend on their biogenesis, uptake, and composition. Thus, a deeper understanding of these processes and regulatory mechanisms can help to find new targets for disease diagnosis and therapy. Therefore, this review summarizes and integrates the recent advances in the regulatory mechanisms of the entire biological process of exosomes, starting from the formation of early-sorting endosomes (ESCs) by plasma membrane invagination to the release of exosomes by fusion of multivesicular bodies (MVBs) with the plasma membrane, as well as the regulatory process of the interactions between exosomes and recipient cells. We also describe and discuss the regulatory mechanisms of exosome production in tumor cells and the potential of exosomes used in cancer diagnosis and therapy. Full article

(This article belongs to the Special Issue The Molecular Basis of Extracellular Vesicles in Health and Diseases)

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