Extracellular Vesicles in Health and Disease 2023

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 15 June 2024 | Viewed by 8451

Special Issue Editors


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Guest Editor
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
Interests: neuroblastoma; breast cancer; extracellular vesicles; cancer signaling; Wnt; metastasis intercellular communication; EMT; proteomics

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Guest Editor
Department of Biomedical Sciences, Catholic Kwandong University, Gangneung, Republic of Korea
Interests: neuronal differentiation; neural precursor cells; ischemic stroke; mesenchymal stem cells; extracellular vesicles; paracrine effects; proteomics

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Guest Editor
Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
Interests: cancer cachexia; extracellular vesicles; muscle atrophy; colon cancer; pancreatic cancer; biomarkers; proteomics; infectious diseases

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) are heterogenous, phospholipid membrane-enclosed structures that are released by all eukaryotic and prokaryotic cells into the extracellular matrix under both physiological and pathological conditions. These nano-sized vesicles are 30–5000 nm in size and broadly classified into small and large EVs based on operational terms such as cell of origin, size, and biochemical composition. EVs contain a rich and diverse cargo of proteins, lipids, nucleic acids, and metabolites through which they mediate intercellular communication. The last few years have witnessed major development in EV research, including their role in numerous physiological processes such as immune regulation, tissue homeostasis, and development and pathological processes such as autoimmunity, neurodegenerative, cardiovascular, infectious, and neoplastic diseases. Apart from their role in disease pathology, EVs and their cargo have been proposed as reservoirs of biomarkers for various diseases. Furthermore, several studies have shed light on the significance of EVs as drug targets and delivery vehicles for treatment.

The aim of this Special Issue is to highlight the role of extracellular vesicles in various diseases, from disease pathology to diagnosis and treatment. We would like to invite experts to submit their unpublished original research and reviews with a comprehensive overview of EVs in health and diseases.

Dr. Pamali Fonseka
Dr. Han-soo Kim
Dr. Sai Vara Prasad Chitti
Guest Editors

Manuscript Submission Information

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Keywords

  • extracellular vesicles
  • cancer
  • cardiovascular diseases
  • neurodegenerative diseases
  • autoimmunity and transplantation
  • innate immunity and inflammation
  • immunoregulation
  • infectious diseases

Published Papers (5 papers)

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Research

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22 pages, 9476 KiB  
Article
Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-β- and PDGF-B-Mediated Fibrotic Processes
by Beáta Szebeni, Apor Veres-Székely, Domonkos Pap, Péter Bokrossy, Zoltán Varga, Anikó Gaál, Judith Mihály, Éva Pállinger, István M. Takács, Csenge Pajtók, Mária Bernáth, György S. Reusz, Attila J. Szabó and Ádám Vannay
Cells 2024, 13(7), 605; https://doi.org/10.3390/cells13070605 - 29 Mar 2024
Viewed by 866
Abstract
Among patients on peritoneal dialysis (PD), 50–80% will develop peritoneal fibrosis, and 0.5–4.4% will develop life-threatening encapsulating peritoneal sclerosis (EPS). Here, we investigated the role of extracellular vesicles (EVs) on the TGF-β- and PDGF-B-driven processes of peritoneal fibrosis. EVs were isolated from the [...] Read more.
Among patients on peritoneal dialysis (PD), 50–80% will develop peritoneal fibrosis, and 0.5–4.4% will develop life-threatening encapsulating peritoneal sclerosis (EPS). Here, we investigated the role of extracellular vesicles (EVs) on the TGF-β- and PDGF-B-driven processes of peritoneal fibrosis. EVs were isolated from the peritoneal dialysis effluent (PDE) of children receiving continuous ambulatory PD. The impact of PDE-EVs on the epithelial–mesenchymal transition (EMT) and collagen production of the peritoneal mesothelial cells and fibroblasts were investigated in vitro and in vivo in the chlorhexidine digluconate (CG)-induced mice model of peritoneal fibrosis. PDE-EVs showed spherical morphology in the 100 nm size range, and their spectral features, CD63, and annexin positivity were characteristic of EVs. PDE-EVs penetrated into the peritoneal mesothelial cells and fibroblasts and reduced their PDE- or PDGF-B-induced proliferation. Furthermore, PDE-EVs inhibited the PDE- or TGF-β-induced EMT and collagen production of the investigated cell types. PDE-EVs contributed to the mesothelial layer integrity and decreased the submesothelial thickening of CG-treated mice. We demonstrated that PDE-EVs significantly inhibit the PDGF-B- or TGF-β-induced fibrotic processes in vitro and in vivo, suggesting that EVs may contribute to new therapeutic strategies to treat peritoneal fibrosis and other fibroproliferative diseases. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Health and Disease 2023)
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15 pages, 1818 KiB  
Article
Isolation and Characterization of Cow-, Buffalo-, Sheep- and Goat-Milk-Derived Extracellular Vesicles
by Monisha Samuel, Rahul Sanwlani, Mohashin Pathan, Sushma Anand, Ella L. Johnston, Ching-Seng Ang, Maria Kaparakis-Liaskos and Suresh Mathivanan
Cells 2023, 12(20), 2491; https://doi.org/10.3390/cells12202491 - 20 Oct 2023
Cited by 2 | Viewed by 1578
Abstract
Milk is a complex biological fluid that has high-quality proteins including growth factors and also contains extracellular vesicles (EVs). EVs are a lipid bilayer containing vesicles that contain proteins, metabolites and nucleic acids. Several studies have proposed that EVs in cow milk can [...] Read more.
Milk is a complex biological fluid that has high-quality proteins including growth factors and also contains extracellular vesicles (EVs). EVs are a lipid bilayer containing vesicles that contain proteins, metabolites and nucleic acids. Several studies have proposed that EVs in cow milk can survive the gut and can illicit cross-species communication in the consuming host organism. In this study, we isolated and characterized extracellular vesicles from the raw milk of the four species of the Bovidae family, namely cow, sheep, goat and buffalo, that contribute 99% of the total milk consumed globally. A comparative proteomic analysis of these vesicles was performed to pinpoint their potential functional role in health and disease. Vesicles sourced from buffalo and cow milk were particularly enriched with proteins implicated in modulating the immune system. Furthermore, functional studies were performed to determine the anti-cancer effects of these vesicles. The data obtained revealed that buffalo-milk-derived EVs induced significantly higher cell death in colon cancer cells. Overall, the results from this study highlight the potent immunoregulatory and anti-cancer nature of EVs derived from the milk of Bovidae family members. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Health and Disease 2023)
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27 pages, 8740 KiB  
Article
Cardiac Progenitor Cell Exosomal miR-935 Protects against Oxidative Stress
by Susana Aguilar, Paula García-Olloqui, Lidia Amigo-Morán, José Luis Torán, Juan Antonio López, Guillermo Albericio, Gloria Abizanda, Diego Herrero, África Vales, Saray Rodríguez-Diaz, Marina Higuera, Rubén García-Martín, Jesús Vázquez, Carmen Mora, Gloria González-Aseguinolaza, Felipe Prosper, Beatriz Pelacho and Antonio Bernad
Cells 2023, 12(18), 2300; https://doi.org/10.3390/cells12182300 - 18 Sep 2023
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Abstract
Oxidative stress-induced myocardial apoptosis and necrosis are critically involved in ischemic infarction, and several sources of extracellular vesicles appear to be enriched in therapeutic activities. The central objective was to identify and validate the differential exosome miRNA repertoire in human cardiac progenitor cells [...] Read more.
Oxidative stress-induced myocardial apoptosis and necrosis are critically involved in ischemic infarction, and several sources of extracellular vesicles appear to be enriched in therapeutic activities. The central objective was to identify and validate the differential exosome miRNA repertoire in human cardiac progenitor cells (CPC). CPC exosomes were first analyzed by LC-MS/MS and compared by RNAseq with exomes of human mesenchymal stromal cells and human fibroblasts to define their differential exosome miRNA repertoire (exo-miRSEL). Proteomics demonstrated a highly significant representation of cardiovascular development functions and angiogenesis in CPC exosomes, and RNAseq analysis yielded about 350 different miRNAs; among the exo-miRSEL population, miR-935 was confirmed as the miRNA most significantly up-regulated; interestingly, miR-935 was also found to be preferentially expressed in mouse primary cardiac Bmi1+high CPC, a population highly enriched in progenitors. Furthermore, it was found that transfection of an miR-935 antagomiR combined with oxidative stress treatment provoked a significant increment both in apoptotic and necrotic populations, whereas transfection of a miR-935 mimic did not modify the response. Conclusion. miR-935 is a highly differentially expressed miRNA in exo-miRSEL, and its expression reduction promotes oxidative stress-associated apoptosis. MiR-935, together with other exosomal miRNA members, could counteract oxidative stress-related apoptosis, at least in CPC surroundings. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Health and Disease 2023)
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Review

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17 pages, 2021 KiB  
Review
Unravelling the Role of Cancer Cell-Derived Extracellular Vesicles in Muscle Atrophy, Lipolysis, and Cancer-Associated Cachexia
by Akbar L. Marzan and Sai V. Chitti
Cells 2023, 12(22), 2598; https://doi.org/10.3390/cells12222598 - 9 Nov 2023
Cited by 1 | Viewed by 1681
Abstract
Cancer-associated cachexia is a metabolic syndrome that causes significant reduction in whole-body weight due to excessive loss of muscle mass accompanied by loss of fat mass. Reduced food intake and several metabolic abnormalities, such as increased energy expenditure, excessive catabolism, and inflammation, are [...] Read more.
Cancer-associated cachexia is a metabolic syndrome that causes significant reduction in whole-body weight due to excessive loss of muscle mass accompanied by loss of fat mass. Reduced food intake and several metabolic abnormalities, such as increased energy expenditure, excessive catabolism, and inflammation, are known to drive cachexia. It is well documented that cancer cells secrete EVs in abundance which can be easily taken up by the recipient cell. The cargo biomolecules carried by the EVs have the potential to alter the signalling pathways and function of the recipient cells. EV cargo includes proteins, nucleic acids, lipids, and metabolites. Tumour-secreted EVs have been found to alter the metabolic and biological functions of adipose and muscle tissue, which aids in the development of the cachexia phenotype. To date, no medical intervention or FDA-approved drug exists that can completely reverse cachexia. Therefore, understanding how cancer-derived EVs contribute to the onset and progression of cancer-associated cachexia may help with the identification of new biomarkers as well as provide access to novel treatment alternatives. The goal of this review article is to discuss the most recent research on cancer-derived EVs and their function in cellular crosstalk that promotes catabolism in muscle and adipose tissue during cancer-induced cachexia. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Health and Disease 2023)
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17 pages, 1802 KiB  
Review
Role of Endometrial Extracellular Vesicles in Mediating Cell-to-Cell Communication in the Uterus: A Review
by Jacob R. Beal, Qiuyan Ma, Indrani C. Bagchi and Milan K. Bagchi
Cells 2023, 12(22), 2584; https://doi.org/10.3390/cells12222584 - 7 Nov 2023
Cited by 3 | Viewed by 1852
Abstract
There are several critical events that occur in the uterus during early pregnancy which are necessary for the establishment and maintenance of pregnancy. These events include blastocyst implantation, uterine decidualization, uterine neoangiogenesis, differentiation of trophoblast stem cells into different trophoblast cell lineages, and [...] Read more.
There are several critical events that occur in the uterus during early pregnancy which are necessary for the establishment and maintenance of pregnancy. These events include blastocyst implantation, uterine decidualization, uterine neoangiogenesis, differentiation of trophoblast stem cells into different trophoblast cell lineages, and formation of a placenta. These processes involve several different cell types within the pregnant uterus. Communication between these cell types must be intricately coordinated for successful embryo implantation and the formation of a functional maternal–fetal interface in the placenta. Understanding how this intricate coordination transpires has been a focus of researchers in the field for many years. It has long been understood that maternal endometrial tissue plays a key role in intercellular signaling during early pregnancy, sending signals to nearby tissues in a paracrine manner. Recently, insights have been obtained into the mechanisms by which these signaling events occur. Notably, the endometrium has been shown to secrete extracellular vesicles (EVs) that contain crucial cargo (proteins, lipids, RNA, miRNA) that are taken up by recipient cells to initiate a response leading to the occurrence of critical events during implantation and placentation. In this review, we aim to summarize the role that endometrium-derived EVs play in mediating cell-to-cell communications within the pregnant uterus to orchestrate the events that must occur to establish and maintain pregnancy. We will also discuss how aberrant endometrial EV signaling may lead to pathophysiological conditions, such as endometriosis and infertility. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Health and Disease 2023)
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