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Roles and Use of Extracellular Vesicles in Health and Disease
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Roles and Use of Extracellular Vesicles in Health and Disease

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Cell Biology".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 12381

Special Issue Editors

Dr. Arsalan Haqqani

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Guest Editor
Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON K2T0A8, Canada
Interests: proteomics; biomarkers; blood brain barrier; Alzheimer’s disease
Dr. Amanpreet Badhwar

E-Mail Website
Guest Editor
Centre de Recherche, Institut Universitaire de Gériatrie de Montréal, Université de Montréal, Montréal, QC H3W1W5, Canada
Interests: Alzheimer’s disease; neuroimaging; proteomics; cerebrovascular damage

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) are diverse, nanoscale membrane vesicles released by a variety of cells into the extracellular microenvironment. EVs represent a mechanism of cell-to-cell communication through the direct stimulation of cells via receptor-mediated contact and/or through the transfer of genetic material (DNA, RNAs), proteins, and lipids. EVs display versatile physiological functions and are involved in the regulation of main routes of signaling and intercellular information transfer between different cell types, possibly even cross-kingdom. However, EVs are also key players in various pathological functions and are involved in many diseases, including inflammation, cancer, diabetes, cardiovascular and cerberovascular diseases, autoimmune diseases, renal failure, and many disorders of the central nervous system. EVs are also excellent candidates as a source of biomarkers in these diseases as their cargoes reflect the pathophysiological signatures of the cell of origin. Finally, EVs are attracting much interest as a platform for therapeutic development in many diseases.

The purpose of this Special Issue is to convey current understanding about extracellular vesicles (EVs) and their role in health and disease, as well as to investigate recent advancements in the field and provide an overview of EVs' usage as therapeutic delivery vehicles in various diseases. Original review and research articles are welcome.

Dr. Arsalan Haqqani
Dr. Amanpreet Badhwar
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. Biology is an international peer-reviewed open access monthly 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 (EVs)
  • cellular biology
  • inflammation
  • diseases
  • biomarkers

Published Papers (5 papers)

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Research

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21 pages, 2060 KiB  
Article
Proteome Profiling of Brain Vessels in a Mouse Model of Cerebrovascular Pathology
by Arsalan S. Haqqani, Zainab Mianoor, Alexandra T. Star, Flavie E. Detcheverry, Christie E. Delaney, Danica B. Stanimirovic, Edith Hamel and AmanPreet Badhwar
Biology 2023, 12(12), 1500; https://0-doi-org.brum.beds.ac.uk/10.3390/biology12121500 - 07 Dec 2023
Viewed by 1478
Abstract
Cerebrovascular pathology that involves altered protein levels (or signaling) of the transforming growth factor beta (TGFβ) family has been associated with various forms of age-related dementias, including Alzheimer disease (AD) and vascular cognitive impairment and dementia (VCID). Transgenic mice overexpressing TGFβ1 in the [...] Read more.
Cerebrovascular pathology that involves altered protein levels (or signaling) of the transforming growth factor beta (TGFβ) family has been associated with various forms of age-related dementias, including Alzheimer disease (AD) and vascular cognitive impairment and dementia (VCID). Transgenic mice overexpressing TGFβ1 in the brain (TGF mice) recapitulate VCID-associated cerebrovascular pathology and develop cognitive deficits in old age or when submitted to comorbid cardiovascular risk factors for dementia. We characterized the cerebrovascular proteome of TGF mice using mass spectrometry (MS)-based quantitative proteomics. Cerebral arteries were surgically removed from 6-month-old-TGF and wild-type mice, and proteins were extracted and analyzed by gel-free nanoLC-MS/MS. We identified 3602 proteins in brain vessels, with 20 demonstrating significantly altered levels in TGF mice. For total and/or differentially expressed proteins (p ≤ 0.01, ≥ 2-fold change), using multiple databases, we (a) performed protein characterization, (b) demonstrated the presence of their RNA transcripts in both mouse and human cerebrovascular cells, and (c) demonstrated that several of these proteins were present in human extracellular vesicles (EVs) circulating in blood. Finally, using human plasma, we demonstrated the presence of several of these proteins in plasma and plasma EVs. Dysregulated proteins point to perturbed brain vessel vasomotricity, remodeling, and inflammation. Given that blood-isolated EVs are novel, attractive, and a minimally invasive biomarker discovery platform for age-related dementias, several proteins identified in this study can potentially serve as VCID markers in humans. Full article
(This article belongs to the Special Issue Roles and Use of Extracellular Vesicles in Health and Disease)
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20 pages, 2354 KiB  
Article
Circulating Small RNA Profiling of Patients with Alveolar and Cystic Echinococcosis
by Marcela A. Cucher, Mara Mariconti, Tommaso Manciulli, Ambra Vola, Mara C. Rosenzvit, Klaus Brehm, Laura Kamenetzky and Enrico Brunetti
Biology 2023, 12(5), 715; https://0-doi-org.brum.beds.ac.uk/10.3390/biology12050715 - 13 May 2023
Cited by 1 | Viewed by 1394
Abstract
Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, [...] Read more.
Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers for several diseases. Here, we profiled the sRNA transcriptomes of AE and CE patients to identify novel biomarkers to aid in medical decisions when current diagnostic procedures are inconclusive. For this, endogenous and parasitic sRNAs were analyzed by sRNA sequencing in serum from disease negative, positive, and treated patients and patients harboring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE, and/or non-parasitic lesion were identified. Our results represent an in-depth characterization of the effect E. multilocularis and E. granulosus s. l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection. Full article
(This article belongs to the Special Issue Roles and Use of Extracellular Vesicles in Health and Disease)
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14 pages, 3960 KiB  
Article
Extracellular Vesicles Cargo in Modulating Microglia Functional Responses
by Maria Ester La Torre, Maria Antonietta Panaro, Melania Ruggiero, Rita Polito, Antonia Cianciulli, Francesca Martina Filannino, Dario Domenico Lofrumento, Laura Antonucci, Tarek Benameur, Vincenzo Monda, Marcellino Monda, Chiara Porro and Giovanni Messina
Biology 2022, 11(10), 1426; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11101426 - 29 Sep 2022
Cited by 2 | Viewed by 1740
Abstract
Extracellular vesicles (EVs) represent a heterogeneous group of membranous structures derived from cells that are released by all cell types, including brain cells. EVs are now thought to be an additional mechanism of intercellular communication. Both under normal circumstances and following the addition [...] Read more.
Extracellular vesicles (EVs) represent a heterogeneous group of membranous structures derived from cells that are released by all cell types, including brain cells. EVs are now thought to be an additional mechanism of intercellular communication. Both under normal circumstances and following the addition of proinflammatory stimuli, microglia release EVs, but the contents of these two types of EVs are different. Microglia are considered the brain-resident immune cells that are involved in immune surveillance and inflammatory responses in the central nervous system. In this research, we have analyzed the effects of EVs isolated from microglia in response to LPS (Lipopolysaccharide) on microglia activation. The EVs produced as result of LPS stimulation, knows as EVs-LPS, were then used as stimuli on microglia BV2 resting cells in order to investigate their ability to induce microglia to polarize towards an inflammatory state. After EVs-LPS stimulation, we analyzed the change to BV2 cells’ morphology, proliferation, and migration, and investigated the expression and the release of pro-inflammatory cytokines. The encouraging findings of this study showed that EVs-LPS can activate microglia in a manner similar to that of LPS alone and that EVs derived from control cells cannot polarize microglia towards a pro-inflammatory state. This study has confirmed the critical role of EVs in communication and shown how EVs produced in an inflammatory environment can exacerbate the inflammatory process by activating microglia, which may have an impact on all brain cells. Full article
(This article belongs to the Special Issue Roles and Use of Extracellular Vesicles in Health and Disease)
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20 pages, 4222 KiB  
Article
Extracellular Vesicles Derived from Mesenchymal Stromal Cells Delivered during Hypothermic Oxygenated Machine Perfusion Repair Ischemic/Reperfusion Damage of Kidneys from Extended Criteria Donors
by Teresa Rampino, Marilena Gregorini, Giuliana Germinario, Eleonora Francesca Pattonieri, Fulvia Erasmi, Maria Antonietta Grignano, Stefano Bruno, Esra Alomari, Stefano Bettati, Annalia Asti, Marina Ramus, Mara De Amici, Giorgia Testa, Stefania Bruno, Gabriele Ceccarelli, Nicoletta Serpieri, Carmelo Libetta, Vincenzo Sepe, Flavia Blasevich, Federica Odaldi, Lorenzo Maroni, Francesco Vasuri, Gaetano La Manna and Matteo Ravaioliadd Show full author list remove Hide full author list
Biology 2022, 11(3), 350; https://doi.org/10.3390/biology11030350 - 22 Feb 2022
Cited by 19 | Viewed by 3710
Abstract
The poor availability of kidney for transplantation has led to a search for new strategies to increase the donor pool. The main option is the use of organs from extended criteria donors. We evaluated the effects of hypothermic oxygenated perfusion (HOPE) with and [...] Read more.
The poor availability of kidney for transplantation has led to a search for new strategies to increase the donor pool. The main option is the use of organs from extended criteria donors. We evaluated the effects of hypothermic oxygenated perfusion (HOPE) with and without extracellular vesicles (EV) derived from mesenchymal stromal cells on ischemic/reperfusion injury of marginal kidneys unsuitable for transplantation. For normothermic reperfusion (NR), we used artificial blood as a substitute for red blood cells. We evaluated the global renal ischemic dam-age score (GRS), analyzed the renal ultrastructure (RU), cytochrome c oxidase (COX) IV-1 (a mitochondrial distress marker), and caspase-3 renal expression, the tubular cell proliferation index, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) tissue levels, and effluent lactate and glucose levels. HOPE+EV kidneys had lower GRS and better RU, higher COX IV-1 expression and HGF and VEGF levels and lower caspase-3 expression than HOPE kidneys. During NR, HOPE+EV renal effluent had lower lactate release and higher glucose levels than HOPE renal effluent, suggesting that the gluconeogenesis system in HOPE+EV group was pre-served. In conclusion, EV delivery during HOPE can be considered a new organ preservation strategy for increasing the donor pool and improving transplant outcome. Full article
(This article belongs to the Special Issue Roles and Use of Extracellular Vesicles in Health and Disease)
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Review

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22 pages, 1114 KiB  
Review
Mechanisms and Biomarker Potential of Extracellular Vesicles in Stroke
by Nikita Ollen-Bittle, Austyn D. Roseborough, Wenxuan Wang, Jeng-liang D. Wu and Shawn N. Whitehead
Biology 2022, 11(8), 1231; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11081231 - 18 Aug 2022
Cited by 8 | Viewed by 3030
Abstract
Stoke is a prevalent and devastating neurologic condition with limited options for therapeutic management. Since brain tissue is rarely accessible clinically, peripheral biomarkers for the central nervous system’s (CNS’s) cellular response to stroke may prove critical for increasing our understanding of stroke pathology [...] Read more.
Stoke is a prevalent and devastating neurologic condition with limited options for therapeutic management. Since brain tissue is rarely accessible clinically, peripheral biomarkers for the central nervous system’s (CNS’s) cellular response to stroke may prove critical for increasing our understanding of stroke pathology and elucidating novel therapeutic targets. Extracellular vesicles (EVs) are cell-derived, membrane-enclosed vesicles secreted by all cell types within the CNS that can freely pass the blood-brain barrier (BBB) and contain unique markers and content linked to their cell of origin. These unique qualities make brain-derived EVs novel candidates for non-invasive blood-based biomarkers of both cell specificity and cell physiological state during the progression of stroke and recovery. While studies are continuously emerging that are assessing the therapeutic potential of EVs and profiling EV cargo, a vast minority of these studies link EV content to specific cell types. A better understanding of cell-specific EV release during the acute, subacute, and chronic stages of stroke is needed to further elucidate the cellular processes responsible for stroke pathophysiology. Herein, we outline what is known about EV release from distinct cell types of the CNS during stroke and the potential of these EVs as peripheral biomarkers for cellular function in the CNS during stroke. Full article
(This article belongs to the Special Issue Roles and Use of Extracellular Vesicles in Health and Disease)
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