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Cells
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Extracellular Vesicles (EVs) in Diseases
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Extracellular Vesicles (EVs) in Diseases

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 13441

Special Issue Editors

Dr. Fabiana Geraci

E-Mail Website
Guest Editor
Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy
Interests: extracellular vesicles; stem cells; heat shock response; Hsp70; neurodegenerative disease; multiple sclerosis
Dr. Maria Magdalena Barreca

E-Mail Website
Guest Editor
Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Section of Biology and Genetics, University of Palermo, 90133 Palermo, Italy
Interests: extracellular vesicles; stem cells; multiple sclerosis; exo-ncRNAs; RNA-binding protein; cancer biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As is well known, extracellular vesicles (EVs) are small lipid particles secreted by almost all cell types. They are abundant in body fluids such as blood, urine, spinal fluid, milk, tears, and saliva, and in cell culture media. 

Recently, the field of EV research has been intensively expanding, as indicated by the rapid increase in the number of EV-related publications collected in EVpedia (http://evpedia.info), a community web portal for extracellular vesicle research.

EVs have received considerable attention as messengers of intercellular communication networks, allowing the exchange of proteins, metabolites and lipids between releasing cells and target cells that trigger various cellular responses. EVs also carry several types of RNAs, horizontally transferring genetic information among cells. Moreover, in both physiological and pathological conditions, EV content is related to cellular state or disease progression. For this reason, the search for biomarkers within EVs is underway in many research fields. However, the physiological and pathophysiological roles of EVs remain largely elusive. 

In this Special Issue, we welcome manuscripts addressing original research and review papers as well as short communications highlighting the roles of EVs:

  • As diagnostic and prognostic biomarkers;
  • As next-generation drug delivery platforms;
  • In tissue regeneration;
  • As indicators of treatment efficacy;
  • In immunological response.

Dr. Fabiana Geraci
Dr. Maria Magdalena Barreca
Guest Editors

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. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • extracellular vesicles
  • biomarkers
  • liquid biopsy
  • human diseases
  • drug delivery
  • therapeutic targets
  • tissue repair

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Published Papers (5 papers)

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Research

Jump to: Review

21 pages, 4084 KiB  
Article
Altered Extracellular Vesicle-Derived Protein and microRNA Signatures in Bronchoalveolar Lavage Fluid from Patients with Chronic Obstructive Pulmonary Disease
by Sabine Bartel, Justina C. Wolters, Hasnat Noor, Karim Rafie, Jiahua Fang, Benedikt Kirchner, Esther Nolte-′t Hoen, Michael W. Pfaffl, Steven Rutgers, Wim Timens, Maarten van den Berge and Machteld N. Hylkema
Cells 2024, 13(11), 945; https://doi.org/10.3390/cells13110945 - 30 May 2024
Viewed by 1422
Abstract
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease for which there is no cure. Accumulating research results suggest a role for extracellular vesicles (EVs) in the pathogenesis of COPD. This study aimed to uncover the involvement of EVs and their molecular [...] Read more.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease for which there is no cure. Accumulating research results suggest a role for extracellular vesicles (EVs) in the pathogenesis of COPD. This study aimed to uncover the involvement of EVs and their molecular cargo in the progression of COPD by identification of EV-associated protein and microRNA (miRNA) profiles. We isolated EVs from the bronchial alveolar lavage fluid (BALF) of 18 patients with COPD and 11 healthy controls using size-exclusion chromatography. EV isolates were characterized using nanoparticle tracking analysis and protein content. Proteomic analysis revealed a higher abundance of 284 proteins (log2FC > 1) and a lower abundance of 3 proteins (log2FC < −1) in EVs derived from patients with COPD. Ingenuity pathway analysis showed that proteins enriched in COPD-associated EVs trigger inflammatory responses, including neutrophil degranulation. Variances in surface receptors and ligands associated with COPD EVs suggest a preferential interaction with alveolar cells. Small RNAseq analysis identified a higher abundance of ten miRNAs and a lower abundance of one miRNA in EVs from COPD versus controls (Basemean > 100, FDR < 0.05). Our data indicate that the molecular composition of EVs in the BALF of patients with COPD is altered compared to healthy control EVs. Several components in COPD EVs were identified that may perpetuate inflammation and alveolar tissue destruction. Full article
(This article belongs to the Special Issue Extracellular Vesicles (EVs) in Diseases)
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29 pages, 5438 KiB  
Article
Zika Virus-Infected Monocyte Exosomes Mediate Cell-to-Cell Viral Transmission
by Pedro Pablo Martínez-Rojas, Verónica Monroy-Martínez, Lourdes Teresa Agredano-Moreno, Luis Felipe Jiménez-García and Blanca H. Ruiz-Ordaz
Cells 2024, 13(2), 144; https://doi.org/10.3390/cells13020144 - 12 Jan 2024
Cited by 1 | Viewed by 2171
Abstract
Zika fever is a reemerging arthropod-borne viral disease; however, Zika virus (ZIKV) can be transmitted by other, non-vector means. Severe Zika fever is characterized by neurological disorders, autoimmunity, or congenital Zika syndrome. Monocytes are primary ZIKV targets in humans and, in response to [...] Read more.
Zika fever is a reemerging arthropod-borne viral disease; however, Zika virus (ZIKV) can be transmitted by other, non-vector means. Severe Zika fever is characterized by neurological disorders, autoimmunity, or congenital Zika syndrome. Monocytes are primary ZIKV targets in humans and, in response to infection, release extracellular vesicles like exosomes. Exosomes mediate intercellular communication and are involved in the virus’s ability to circumvent the immune response, promoting pathological processes. This study aimed to evaluate the role of monocyte exosomes in cell-to-cell viral transmission. We isolated exosomes from ZIKV-infected monocytes (Mø exo ZIKV) by differential ultracentrifugation and identified them by nanoparticle tracking analysis; transmission electron microscopy; and CD63, CD81, TSG101, and Alix detection by cytofluorometry. Purified exosome isolates were obtained by uncoupling from paramagnetic beads or by treatment with UV radiation and RNase A. We found that Mø exo ZIKV carry viral RNA and E/NS1 proteins and that their interaction with naïve cells favors viral transmission, infection, and cell differentiation/activation. These data suggest that Mø exo ZIKV are an efficient alternative pathway for ZIKV infection. Knowledge of these mechanisms contributes to understanding the pathogenesis of severe disease and to the development of new vaccines and therapies. Full article
(This article belongs to the Special Issue Extracellular Vesicles (EVs) in Diseases)
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14 pages, 6259 KiB  
Article
Identification of YWHAH as a Novel Brain-Derived Extracellular Vesicle Marker Post Long-Term Midazolam Exposure during Early Development
by Nghi M. Nguyen, Daniel Meyer, Luke Meyer, Subhash Chand, Sankarasubramanian Jagadesan, Maireen Miravite, Chittibabu Guda, Sowmya V. Yelamanchili and Gurudutt Pendyala
Cells 2023, 12(6), 966; https://doi.org/10.3390/cells12060966 - 22 Mar 2023
Cited by 2 | Viewed by 2341
Abstract
Recently, the long-term use of sedative agents in the neonatal intensive care unit (NICU) has raised concerns about neurodevelopmental outcomes in exposed neonates. Midazolam (MDZ), a common neonatal sedative in the NICU, has been suggested to increase learning disturbances and cognitive impairment in [...] Read more.
Recently, the long-term use of sedative agents in the neonatal intensive care unit (NICU) has raised concerns about neurodevelopmental outcomes in exposed neonates. Midazolam (MDZ), a common neonatal sedative in the NICU, has been suggested to increase learning disturbances and cognitive impairment in children. However, molecular mechanisms contributing to such outcomes with long-term MDZ use during the early stages of life remain unclear. In this study, we for the first time elucidate the role of brain-derived extracellular vesicles (BDEVs), including mining the BDEV proteome post long-term MDZ exposure during early development. Employing our previously established rodent model system that mimics the exposure of MDZ in the NICU using an increasing dosage regimen, we isolated BDEVs from postnatal 21-days-old control and MDZ groups using a differential sucrose density gradient. BDEVs from the control and MDZ groups were then characterized using a ZetaView nanoparticle tracking analyzer and transmission electron microscopy analysis. Next, using RT-qPCR, we examined the expression of key ESCRT-related genes involved in EV biogenesis. Lastly, using quantitative mass spectrometry-based proteomics, we mined the BDEV protein cargo that revealed key differentially expressed proteins and associated molecular pathways to be altered post long-term MDZ exposure. Our study characterized the proteome in BDEV cargo from long-term MDZ exposure at early development. Importantly, we identified and validated the expression of YWHAH as a potential target for further characterization of its downstream mechanism and a potential biomarker for the early onset of neurodevelopment and neurodegenerative diseases. Overall, the present study demonstrated long-term exposure to MDZ at early development stages could influence BDEV protein cargo, which potentially impact neural functions and behavior at later stages of development. Full article
(This article belongs to the Special Issue Extracellular Vesicles (EVs) in Diseases)
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14 pages, 3057 KiB  
Article
Circulating Microparticles Are Differentially Increased in Lowlanders and Highlanders with High Altitude Induced Pulmonary Hypertension during the Cold Season
by Akylbek Sydykov, Aleksandar Petrovic, Abdirashit M. Maripov, Marija Gredic, Daniel Gerd Bermes, Nadira Kushubakova, Kubatbek Muratali Uulu, Christina Pilz, Meerim Cholponbaeva, Melis Duishobaev, Samatbek Satybaldyev, Nurgul Satieva, Argen Mamazhakypov, Meerim Sartmyrzaeva, Nazgul Omurzakova, Zhainagul Kerimbekova, Nursultan Baktybek, Cholpon Kulchoroeva, Oleg Pak, Lan Zhao, Norbert Weissmann, Sergey Avdeev, Leonid N. Maslov, Hossein Ardeschir Ghofrani, Ralph Theo Schermuly, Akpay S. Sarybaev and Djuro Kosanovicadd Show full author list remove Hide full author list
Cells 2022, 11(19), 2932; https://doi.org/10.3390/cells11192932 - 20 Sep 2022
Cited by 2 | Viewed by 2389
Abstract
The role of microparticles (MPs) and cold in high altitude pulmonary hypertension (HAPH) remains unexplored. We investigated the impact of long-term cold exposure on the pulmonary circulation in lowlanders and high-altitude natives and the role of MPs. Pulmonary hemodynamics were evaluated using Doppler [...] Read more.
The role of microparticles (MPs) and cold in high altitude pulmonary hypertension (HAPH) remains unexplored. We investigated the impact of long-term cold exposure on the pulmonary circulation in lowlanders and high-altitude natives and the role of MPs. Pulmonary hemodynamics were evaluated using Doppler echocardiography at the end of the colder and warmer seasons. We further examined the miRNA content of MPs isolated from the study participants and studied their effects on human pulmonary artery smooth muscle (hPASMCs) and endothelial cells (hPAECs). Long-term exposure to cold environment was associated with an enhanced pulmonary artery pressure in highlanders. Plasma levels of CD62E-positive and CD68-positive MPs increased in response to cold in lowlanders and HAPH highlanders. The miRNA-210 expression contained in MPs differentially changed in response to cold in lowlanders and highlanders. MPs isolated from lowlanders and highlanders increased proliferation and reduced apoptosis of hPASMCs. Further, MPs isolated from warm-exposed HAPH highlanders and cold-exposed highlanders exerted the most pronounced effects on VEGF expression in hPAECs. We demonstrated that prolonged exposure to cold is associated with elevated pulmonary artery pressures, which are most pronounced in high-altitude residents. Further, the numbers of circulating MPs are differentially increased in lowlanders and HAPH highlanders during the colder season. Full article
(This article belongs to the Special Issue Extracellular Vesicles (EVs) in Diseases)
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Review

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22 pages, 2220 KiB  
Review
The Role of Exosomes in Human Carcinogenesis and Cancer Therapy—Recent Findings from Molecular and Clinical Research
by Katarzyna Stefańska, Małgorzata Józkowiak, Ana Angelova Volponi, Jamil Awad Shibli, Afsaneh Golkar-Narenji, Paweł Antosik, Dorota Bukowska, Hanna Piotrowska-Kempisty, Paul Mozdziak, Piotr Dzięgiel, Marzenna Podhorska-Okołów, Maciej Zabel, Marta Dyszkiewicz-Konwińska and Bartosz Kempisty
Cells 2023, 12(3), 356; https://doi.org/10.3390/cells12030356 - 18 Jan 2023
Cited by 18 | Viewed by 3731
Abstract
Exosomes are biological nanoscale spherical lipid bilayer vesicles, 40–160 nm in diameter, produced by most mammalian cells in both physiological and pathological conditions. Exosomes are formed via the endosomal sorting complex required for transport (ESCRT). The primary function of exosomes is mediating cell-to-cell [...] Read more.
Exosomes are biological nanoscale spherical lipid bilayer vesicles, 40–160 nm in diameter, produced by most mammalian cells in both physiological and pathological conditions. Exosomes are formed via the endosomal sorting complex required for transport (ESCRT). The primary function of exosomes is mediating cell-to-cell communication. In terms of cancer, exosomes play important roles as mediators of intercellular communication, leading to tumor progression. Moreover, they can serve as biomarkers for cancer detection and progression. Therefore, their utilization in cancer therapies has been suggested, either as drug delivery carriers or as a diagnostic tool. However, exosomes were also reported to be involved in cancer drug resistance via transferring information of drug resistance to sensitive cells. It is important to consider the current knowledge regarding the role of exosomes in cancer, drug resistance, cancer therapies, and their clinical application in cancer therapies. Full article
(This article belongs to the Special Issue Extracellular Vesicles (EVs) in Diseases)
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