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The Role of Extracellular Vesicles in Aging and Disease
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The Role of Extracellular Vesicles in Aging and 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: closed (30 January 2023) | Viewed by 16934

Special Issue Editors

Prof. Dr. Consuelo Borras

E-Mail Website
Guest Editor
Department of Physiology, Faculty of Medicine, University of Valencia, Avenida Blasco Ibañez 15, 46010 Valencia, Spain
Interests: aging; senescence; stem cells; oxidative stress; sex
Special Issues, Collections and Topics in MDPI journals
Dr. Cristina Mas-Bargues

E-Mail Website
Guest Editor
Department of Physiology, Faculty of Medicine, University of Valencia, Avenida Blasco Ibañez 15, 46010 Valencia, Spain
Interests: stem cells; physioxia; oxidative stress; senescence; apoptosis; autophagy; aging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As cells accumulate damage over time, they respond by individual cell fate decisions that disrupt tissue homeostasis, thus leading to organ dysfunction and increased morbidity. Extracellular vesicles (EVs) are known to be able to modulate the aging process by restoring the microenvironment and promoting tissue regeneration. Thus, EVs are promising therapeutic tools, especially in the field of aging and diseases.

However, there is still a long way before EVs can be used at the clinic. Standardization of the methodology, reproducibility and data comparison are major outcomes that must be improved in order to achieve EV-based therapeutics. Therefore, in this Special Issue, we encourage scientists to contribute original articles or reviews describing EV sources, collection and purification methods, as well as EV synthetic designs, such as drug delivery carriers.

Since EV bioactive cargo (proteins, miRNA, lipids) is altered depending on the physio-pathological conditions, we are also looking for studies on EVs’ functional effect on target cells and the underlying mechanisms or signaling pathways that are involved in the process. Finally, we will also welcome research on EV applications for expanding health span, as well as EV use as early biomarkers for disease detection.

Prof. Dr. Consuelo Borras
Dr. Cristina Mas-Bargues
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. 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

  • extracellular vesicles
  • EV-based therapeutics
  • aging
  • disease
  • biomarkers
  • regenerative medicine
  • stem cells

Published Papers (7 papers)

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Editorial

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3 pages, 202 KiB  
Editorial
The Role of Extracellular Vesicles in Aging and Disease
by Consuelo Borrás and Cristina Mas-Bargues
Int. J. Mol. Sci. 2023, 24(18), 13739; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241813739 - 06 Sep 2023
Viewed by 779
Abstract
Cells are exposed to various internal and external factors that can cause damage over time [...] Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Aging and Disease)

Research

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14 pages, 4879 KiB  
Article
Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension
by Juliana Pena Lopez, Mohammad-Zaman Nouri, Areej Ebrahim, Kevin M. Chacko, Whitney C. Schramm, Mohammed F. Gholam, Tezcan Ozrazgat-Baslanti, Nancy D. Denslow and Abdel A. Alli
Int. J. Mol. Sci. 2022, 23(23), 15397; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232315397 - 06 Dec 2022
Cited by 4 | Viewed by 1394
Abstract
Hypertension remains a major problem, especially in the elderly, as it increases the risk for cardiovascular, coronary artery, cerebrovascular, and kidney diseases. Extracellular vesicles (EVs) play a role in the aging process and contribute to pathophysiology. Our goal was to examine differences in [...] Read more.
Hypertension remains a major problem, especially in the elderly, as it increases the risk for cardiovascular, coronary artery, cerebrovascular, and kidney diseases. Extracellular vesicles (EVs) play a role in the aging process and contribute to pathophysiology. Our goal was to examine differences in lipid profiles of urinary EVs (uEVs) collected during the inactive and active phases of aged mice and investigate whether these EVs regulate the density of lipid rafts in mouse cortical collecting duct (mpkCCD) principal cells. Here, we demonstrate the epithelial sodium channel (ENaC) inhibitor benzyl amiloride reduced systolic blood pressure in aged male mice during the inactive and active phases. Lipidomics data demonstrate differential enrichment of lipids between the two groups. For example, there are more phosphatidylethanolamine plasmalogens, particularly in the form of alkyl phosphatidylethanolamines, that are enriched in active phase uEVs compared to inactive phase uEVs from the same mice. Amiloride-sensitive transepithelial current increased more in mpkCCD cells challenged with uEVs from the active phase group. Moreover, more ENaC alpha protein was distributed to lipid raft fractions of mpkCCD cells challenged with active phase uEVs. Taken together, the identification of bioactive lipids associated with lipid rafts that are enriched in EVs released during the active phase of aged mice may offer clues to help understand lipid raft organization in recipient principal cells after EV uptake and increased renal ENaC activity, leading to a time-of-day dependent regulation of blood pressure in an aging model. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Aging and Disease)
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25 pages, 4253 KiB  
Article
Distinct Exosomal miRNA Profiles from BALF and Lung Tissue of COPD and IPF Patients
by Gagandeep Kaur, Krishna Prahlad Maremanda, Michael Campos, Hitendra S. Chand, Feng Li, Nikhil Hirani, M. A. Haseeb, Dongmei Li and Irfan Rahman
Int. J. Mol. Sci. 2021, 22(21), 11830; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111830 - 31 Oct 2021
Cited by 36 | Viewed by 3745
Abstract
Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic, progressive lung ailments that are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Extracellular vesicles (EVs), including exosomes, are small, lipid-bound vesicles attributed [...] Read more.
Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic, progressive lung ailments that are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Extracellular vesicles (EVs), including exosomes, are small, lipid-bound vesicles attributed to carry proteins, lipids, and RNA molecules to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of bronchoalveolar lavage fluid (BALF) or the lung-tissue-derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF- and lung-tissue-derived exosomes of healthy non-smokers, smokers, and patients with COPD or IPF in independent cohorts. Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were ~89.85 nm in size with a yield of ~2.95 × 1010 particles/mL in concentration. Lung-derived exosomes were larger in size (~146.04 nm) with a higher yield of ~2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while there was one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, miR-122-5p was three- or five-fold downregulated among the lung-tissue-derived exosomes of COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were a large number (55) of differentially expressed miRNAs in the lung-tissue-derived exosomes of IPF patients compared to non-smoking controls. Conclusions: Overall, we identified lung-specific miRNAs associated with chronic lung diseases that can serve as potential biomarkers or therapeutic targets. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Aging and Disease)
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Review

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17 pages, 1771 KiB  
Review
Mitochondrial-Derived Vesicles: The Good, the Bad, and the Ugly
by Anna Picca, Flora Guerra, Riccardo Calvani, Hélio José Coelho-Júnior, Francesco Landi, Cecilia Bucci and Emanuele Marzetti
Int. J. Mol. Sci. 2023, 24(18), 13835; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241813835 - 08 Sep 2023
Cited by 4 | Viewed by 1909
Abstract
Mitophagy is crucial for maintaining mitochondrial quality. However, its assessment in vivo is challenging. The endosomal–lysosomal system is a more accessible pathway through which subtypes of extracellular vesicles (EVs), which also contain mitochondrial constituents, are released for disposal. The inclusion of mitochondrial components [...] Read more.
Mitophagy is crucial for maintaining mitochondrial quality. However, its assessment in vivo is challenging. The endosomal–lysosomal system is a more accessible pathway through which subtypes of extracellular vesicles (EVs), which also contain mitochondrial constituents, are released for disposal. The inclusion of mitochondrial components into EVs occurs in the setting of mild mitochondrial damage and during impairment of lysosomal function. By releasing mitochondrial-derived vesicles (MDVs), cells limit the unload of mitochondrial damage-associated molecular patterns with proinflammatory activity. Both positive and negative effects of EVs on recipient cells have been described. Whether this is due to the production of EVs other than those containing mitochondria, such as MDVs, holding specific biological functions is currently unknown. Evidence on the existence of different MDV subtypes has been produced. However, their characterization is not always pursued, which would be relevant to exploring the dynamics of mitochondrial quality control in health and disease. Furthermore, MDV classification may be instrumental in understanding their biological roles and promoting their implementation as biomarkers in clinical studies. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Aging and Disease)
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17 pages, 1199 KiB  
Review
The Potential Use of Mitochondrial Extracellular Vesicles as Biomarkers or Therapeutical Tools
by Jorge Sanz-Ros, Cristina Mas-Bargues, Nekane Romero-García, Javier Huete-Acevedo, Mar Dromant and Consuelo Borrás
Int. J. Mol. Sci. 2023, 24(8), 7005; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24087005 - 10 Apr 2023
Cited by 5 | Viewed by 2195
Abstract
The mitochondria play a crucial role in cellular metabolism, reactive oxygen species (ROS) production, and apoptosis. Aberrant mitochondria can cause severe damage to the cells, which have established a tight quality control for the mitochondria. This process avoids the accumulation of damaged mitochondria [...] Read more.
The mitochondria play a crucial role in cellular metabolism, reactive oxygen species (ROS) production, and apoptosis. Aberrant mitochondria can cause severe damage to the cells, which have established a tight quality control for the mitochondria. This process avoids the accumulation of damaged mitochondria and can lead to the release of mitochondrial constituents to the extracellular milieu through mitochondrial extracellular vesicles (MitoEVs). These MitoEVs carry mtDNA, rRNA, tRNA, and protein complexes of the respiratory chain, and the largest MitoEVs can even transport whole mitochondria. Macrophages ultimately engulf these MitoEVs to undergo outsourced mitophagy. Recently, it has been reported that MitoEVs can also contain healthy mitochondria, whose function seems to be the rescue of stressed cells by restoring the loss of mitochondrial function. This mitochondrial transfer has opened the field of their use as potential disease biomarkers and therapeutic tools. This review describes this new EVs-mediated transfer of the mitochondria and the current application of MitoEVs in the clinical environment. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Aging and Disease)
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13 pages, 7796 KiB  
Review
The Emerging Role of Extracellular Vesicles Detected in Different Biological Fluids in COPD
by Tommaso Neri, Alessandro Celi, Mariaenrica Tinè, Nicol Bernardinello, Manuel G. Cosio, Marina Saetta, Dario Nieri and Erica Bazzan
Int. J. Mol. Sci. 2022, 23(9), 5136; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23095136 - 05 May 2022
Cited by 5 | Viewed by 2312
Abstract
The pathogenesis of chronic obstructive pulmonary disease (COPD) is characterized by complex cellular and molecular mechanisms, not fully elucidated so far. It involves inflammatory cells (monocytes/macrophages, neutrophils, lymphocytes), cytokines, chemokines and, probably, new players yet to be clearly identified and described. Chronic local [...] Read more.
The pathogenesis of chronic obstructive pulmonary disease (COPD) is characterized by complex cellular and molecular mechanisms, not fully elucidated so far. It involves inflammatory cells (monocytes/macrophages, neutrophils, lymphocytes), cytokines, chemokines and, probably, new players yet to be clearly identified and described. Chronic local and systemic inflammation, lung aging and cellular senescence are key pathological events in COPD development and progression over time. Extracellular vesicles (EVs), released by virtually all cells both as microvesicles and exosomes into different biological fluids, are involved in intercellular communication and, therefore, represent intriguing players in pathobiological mechanisms (including those characterizing aging and chronic diseases); moreover, the role of EVs as biomarkers in different diseases, including COPD, is rapidly gaining recognition. In this review, after recalling the essential steps of COPD pathogenesis, we summarize the current evidence on the roles of EVs collected in different biological mediums as biomarkers in COPD and as potential players in the specific mechanisms leading to disease development. We will also briefly review the data on EV as potential therapeutic targets and potential therapeutic agents. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Aging and Disease)
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23 pages, 1727 KiB  
Review
Extracellular Vesicles and Acute Kidney Injury: Potential Therapeutic Avenue for Renal Repair and Regeneration
by Maja Kosanović, Bojana Milutinovic, Sofija Glamočlija, Ingrid Mena Morlans, Alberto Ortiz and Milica Bozic
Int. J. Mol. Sci. 2022, 23(7), 3792; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073792 - 30 Mar 2022
Cited by 8 | Viewed by 3331
Abstract
Acute kidney injury (AKI) is a sudden decline of renal function and represents a global clinical problem due to an elevated morbidity and mortality. Despite many efforts, currently there are no treatments to halt this devastating condition. Extracellular vesicles (EVs) are nanoparticles secreted [...] Read more.
Acute kidney injury (AKI) is a sudden decline of renal function and represents a global clinical problem due to an elevated morbidity and mortality. Despite many efforts, currently there are no treatments to halt this devastating condition. Extracellular vesicles (EVs) are nanoparticles secreted by various cell types in both physiological and pathological conditions. EVs can arise from distinct parts of the kidney and can mediate intercellular communication between various cell types along the nephron. Besides their potential as diagnostic tools, EVs have been proposed as powerful new tools for regenerative medicine and have been broadly studied as therapeutic mediators in different models of experimental AKI. In this review, we present an overview of the basic features and biological relevance of EVs, with an emphasis on their functional role in cell-to-cell communication in the kidney. We explore versatile roles of EVs in crucial pathophysiological mechanisms contributing to AKI and give a detailed description of the renoprotective effects of EVs from different origins in AKI. Finally, we explain known mechanisms of action of EVs in AKI and provide an outlook on the potential clinical translation of EVs in the setting of AKI. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Aging and Disease)
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