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Extracellular Vesicles in the Pathogenesis of Disease and Their Potential...
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Extracellular Vesicles in the Pathogenesis of Disease and Their Potential Role as Therapeutic Targets

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (20 April 2025) | Viewed by 5100

Special Issue Editor

Dr. Tommaso Neri

E-Mail Website
Guest Editor
Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e di Area Critica e Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
Interests: extracellular vesicles; microparticles; mechanisms underlying microparticle generation; intercellular communication; inflammatory markers; miRNAs; lung inflammation; lung diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) are small, membrane-bound structures released by various cell types into the extracellular environment. Exosomes, microparticles and apoptotic bodies, which differ in composition, biogenesis and size, belong to this family.

EVs have emerged as key players in the pathogenesis of various diseases, influencing disease progression and contributing to intercellular communication within the microenvironment. These small membrane-bound structures carry a cargo of proteins, lipids and nucleic acids, including microRNAs, which can regulate gene expression in recipient cells. Recently, several studies have evaluated the exciting prospect of using EVs as therapeutic targets. Modulating the biogenesis, release and content of EVs may offer promising therapeutic avenues.

With this Special Issue, we invite researchers to contribute with either original research (both in vivo or in vitro studies) or review articles focusing on EVs in the pathogenesis of disease and their potential role as therapeutic targets.

Dr. Tommaso Neri
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.

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Keywords

  • extracellular vesicles
  • exosome
  • microparticles
  • EVs as therapeutic targets
  • EVs in the pathogenesis of disease

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Related Special Issue

Published Papers (4 papers)

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Research

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29 pages, 2363 KiB  
Article
Human Brain Endothelial Cell-Derived Extracellular Vesicles Reduce Toxoplasma gondii Infection In Vitro in Human Brain and Umbilical Cord Vein Endothelial Cells
by Luiz Fernando Cardoso Garcia, Victoria Cruz Cavalari, Pryscilla Fanini Wowk and Letusa Albrecht
Int. J. Mol. Sci. 2025, 26(6), 2640; https://doi.org/10.3390/ijms26062640 - 14 Mar 2025
Viewed by 752
Abstract
The endothelial layer, formed by endothelial cells, performs crucial functions in maintaining homeostasis. The endothelial integrity and function might be compromised due to various causes, including infection by Toxoplasma gondii, leading to an endothelial dysfunction. Toxoplasma gondii is an Apicomplexa parasite that [...] Read more.
The endothelial layer, formed by endothelial cells, performs crucial functions in maintaining homeostasis. The endothelial integrity and function might be compromised due to various causes, including infection by Toxoplasma gondii, leading to an endothelial dysfunction. Toxoplasma gondii is an Apicomplexa parasite that infects a broad range of animals, including humans. This parasite can invade all nucleated cells, as well as endothelial cells. The interaction between this protozoan and endothelial cells can be mediated by different molecules, such as extracellular vesicles (EVs), which may either favor or hinder the infectious process. To investigate this interaction, we evaluated the infection of T. gondii on human brain microvascular endothelial cells (HBMEC) and human umbilical vein endothelial cells (HUVEC), in addition to assessing transcriptional changes. We also featured the EVs secreted by T. gondii and by infected and non-infected HBMEC and HUVEC. Finally, we evaluated the infection of cells stimulated with EVs of parasitic or cellular origin. Our results demonstrated that HUVEC not only exhibit a higher infection rate than HBMEC but also display a more pro-inflammatory transcriptional profile, with increased expression of interleukin-6 (IL6), interleukin-8 (IL8), and monocyte chemotactic protein-1 (MCP1) following infection. Additionally, we observed few differences in the concentration, distribution, and morphology of EVs secreted by both cell types, although their properties in modulating infection varied significantly. When cells were EVs stimulated, EVs from T. gondii promoted an increase in the HBMEC infection, EVs from infected or uninfected HBMEC reduced the infection, whereas EVs from HUVEC had no effect on the infectious process. In conclusion, our data indicate that T. gondii infection induces distinct changes in different endothelial cell types, and EVs from these cells can contribute to the resolution of the infection. Full article
(This article belongs to the Special Issue Extracellular Vesicles in the Pathogenesis of Disease and Their Potential Role as Therapeutic Targets)
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12 pages, 3907 KiB  
Article
Exosomal Prostate-Specific Membrane Antigen (PSMA) and Caveolin-1 as Potential Biomarkers of Prostate Cancer—Evidence from Serbian Population
by Suzana Matijašević Joković, Aleksandra Korać, Sanja Kovačević, Ana Djordjević, Lidija Filipović, Zorana Dobrijević, Miloš Brkušanin, Dušanka Savić-Pavićević, Ivan Vuković, Milica Popović and Goran Brajušković
Int. J. Mol. Sci. 2024, 25(6), 3533; https://doi.org/10.3390/ijms25063533 - 21 Mar 2024
Cited by 3 | Viewed by 2389
Abstract
Prostate-specific membrane antigen (PSMA) and caveolin-1 are membrane proteins that are overexpressed in prostate cancer (PCa) and are involved in tumor growth and increase in aggressiveness. The aim of the present study is therefore to evaluate PSMA and caveolin-1 proteins from plasma exosomes [...] Read more.
Prostate-specific membrane antigen (PSMA) and caveolin-1 are membrane proteins that are overexpressed in prostate cancer (PCa) and are involved in tumor growth and increase in aggressiveness. The aim of the present study is therefore to evaluate PSMA and caveolin-1 proteins from plasma exosomes as effective liquid biopsy biomarkers for PCa. This study included 39 patients with PCa and 33 with benign prostatic hyperplasia (BPH). The shape and size of the exosomes were confirmed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analysis. Immunogold analysis showed that PSMA is localized to the membrane of exosomes isolated from the plasma of both groups of participants. The relative protein levels of PSMA and caveolin-1 in the plasma exosomes of PCa and BPH patients were determined by Western blot analysis. The relative level of the analyzed plasma exosomal proteins was compared between PCa and BPH patients and the relevance of the exosomal PSMA and caveoin-1 level to the clinicopathological parameters in PCa was investigated. The analysis performed showed an enrichment of exosomal PSMA in the plasma of PCa patients compared to the exosomes of men with BPH. The level of exosomal caveolin-1 in plasma was significantly higher in PCa patients with high PSA levels, clinical-stage T3 or T4 and in the group of PCa patients with aggressive PCa compared to favorable clinicopathological features or tumor aggressiveness. Plasma exosomes may serve as a suitable object for the identification of potential biomarkers for the early diagnosis and prognosis of PCa as well as carriers of therapeutic agents in precision medicine of PCa treatment. Full article
(This article belongs to the Special Issue Extracellular Vesicles in the Pathogenesis of Disease and Their Potential Role as Therapeutic Targets)
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Review

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13 pages, 857 KiB  
Review
Extracellular Vesicles as Targeted Communicators in Complementary Medical Treatments
by Keehyun Earm, Yung E. Earm and Denis Noble
Int. J. Mol. Sci. 2025, 26(12), 5896; https://doi.org/10.3390/ijms26125896 - 19 Jun 2025
Viewed by 473
Abstract
The supposed meridians of traditional oriental medicine have been a cause of conflict between traditional and modern medical science. A possible resolution has been proposed: That extracellular vesicles, including exosomes, may be the transmitters of traditional therapies such as massage and acupuncture. This [...] Read more.
The supposed meridians of traditional oriental medicine have been a cause of conflict between traditional and modern medical science. A possible resolution has been proposed: That extracellular vesicles, including exosomes, may be the transmitters of traditional therapies such as massage and acupuncture. This article develops that idea by proposing that the pathways between surface and deep structures may be laid down during the embryonic migration of cells from one region of the developing body to distant regions. This hypothesis depends on the proven targeting of vesicular communication via cell surface binding molecules and their complementary binding sites on target cells. The hypothesis is therefore experimentally testable. The article also draws attention to a strong analogy with Charles Darwin’s theory of pangenesis for particulate communication between the soma and germline. Full article
(This article belongs to the Special Issue Extracellular Vesicles in the Pathogenesis of Disease and Their Potential Role as Therapeutic Targets)
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29 pages, 1440 KiB  
Review
Adaptations of Bacterial Extracellular Vesicles in Response to Antibiotic Pressure
by Dell’Annunziata Federica, Ilaria Cosimato, Flora Salzano, Francesca Mensitieri, Vincenzo Andretta, Emanuela Santoro, Giovanni Boccia, Veronica Folliero and Gianluigi Franci
Int. J. Mol. Sci. 2025, 26(11), 5025; https://doi.org/10.3390/ijms26115025 - 23 May 2025
Viewed by 738
Abstract
Extracellular vesicles (EVs) are nanometer-sized lipid structures actively secreted by Gram-negative and Gram-positive bacteria, representing a sophisticated microbial adaptation and communication strategy. These structures are involved in biomolecular transport, the regulation of biological processes, the modulation of host–pathogen interactions, and adaptation to hostile [...] Read more.
Extracellular vesicles (EVs) are nanometer-sized lipid structures actively secreted by Gram-negative and Gram-positive bacteria, representing a sophisticated microbial adaptation and communication strategy. These structures are involved in biomolecular transport, the regulation of biological processes, the modulation of host–pathogen interactions, and adaptation to hostile environmental conditions. EVs also play a crucial role in virulence, antibiotic resistance, and biofilm formation. This review will explore the biogenesis, composition, and biological mechanisms of outer membrane vesicles (OMVs) secreted by Gram-negative bacteria and membrane vesicles (MVs) generated by Gram-positive bacteria. In detail, the modulation of EVs in response to antibiotic exposure will be addressed. The role of EV morpho-functional adaptations will be studied in antimicrobial resistance, the gene determinant spread, and survival in adverse environments. This study aims to provide a comprehensive overview of the EV role in bacterial physiology, highlighting their ecological, evolutionary, and biotechnological implications. An overview of the enzymes and proteins mainly involved in OMV-mediated resistance mechanisms will also be provided. These insights could open new perspectives for developing therapeutic strategies that counteract EV secretion and biotechnological applications, such as vaccines and drug delivery systems. Full article
(This article belongs to the Special Issue Extracellular Vesicles in the Pathogenesis of Disease and Their Potential Role as Therapeutic Targets)
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