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Exosomes and Extracellular Vesicles in Health and Diseases: 3rd Edition
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Exosomes and Extracellular Vesicles in Health and Diseases: 3rd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 April 2025) | Viewed by 7199

Special Issue Editors

Dr. Manuela Zavatti

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Guest Editor
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Interests: molecular mechanism in cancer; PI3K/Akt signaling; adaptive resistance to Akt inhibitors in prostate cancer; immunomodulatory properties of stem cells extracellular vesicle; neurodegenerative disorders
Special Issues, Collections and Topics in MDPI journals
Dr. Francesca Beretti

E-Mail
Guest Editor
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Interests: exosomes; extracellular vesicles; microRNA; amnion fluid
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The rising interest in exosomes and extracellular vesicles and their applications is reflected by the increasing amount of research on these topics.

These vesicles are naturally produced by any type of cell and play multiple roles in cell-to-cell communication in both healthy and diseased states. Because they carry different donor-derived cargos, including DNA, RNA, proteins and lipids, they induce network signals in recipient cells.

In particular, stem-cell-derived extracellular vesicles play roles in regenerative medicine and have the advantage of being a cell-free therapy; therefore, these vesicles are safer than those associated with the transplantation of live cells.

Furthermore, in recent years, exosomes and extracellular vesicles have emerged as promising biomarkers in the diagnosis and prognosis of different diseases, but also as macromolecule delivery carriers in therapy to treat a wide spectrum of pathologies.

This Special Issue, entitled “Exosomes and Extracellular Vesicles in Health and Diseases 3.0”, welcomes original research articles that broaden our knowledge of extracellular vesicles and exosomes in different fields of application, starting from the healthy state in order to comprehend the mechanisms of individual production and moving onto pathological conditions, such as tumors, neurodegenerative diseases, cardiovascular diseases, chronic and acute inflammatory states, etc.

Dr. Manuela Zavatti
Dr. Francesca Beretti
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

  • exosome
  • extracellular vesicles
  • network signals
  • biomarkers
  • pathological conditions

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Related Special Issues

Published Papers (6 papers)

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Research

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23 pages, 4610 KiB  
Article
Trypanosomatid Extracellular Vesicles as Potential Immunogens for Chagas Disease
by Juliana Bernardi Aggio, Verônica Vitória Vedam, Líndice Mitie Nisimura, Rosiane Valeriano da Silva, Maria Izabel Lovo-Martins, Beatriz Santana Borges, Patrícia Alves Mörking, Michel Batista, Fabricio Klerynton Marchini, Sueli Fumie Yamada-Ogatta, Phileno Pinge-Filho, Samuel Goldenberg, Iriane Eger and Pryscilla Fanini Wowk
Int. J. Mol. Sci. 2025, 26(4), 1544; https://doi.org/10.3390/ijms26041544 - 12 Feb 2025
Viewed by 915
Abstract
Chagas disease remains a significant public health concern, with limited treatment options and an urgent need for novel preventive strategies. Extracellular vesicles (EVs) from Trypanosoma cruzi have been shown to modulate host immune responses, often favoring parasite persistence. In this study, we characterized [...] Read more.
Chagas disease remains a significant public health concern, with limited treatment options and an urgent need for novel preventive strategies. Extracellular vesicles (EVs) from Trypanosoma cruzi have been shown to modulate host immune responses, often favoring parasite persistence. In this study, we characterized EVs derived from the non-pathogenic trypanosomatids Trypanosoma rangeli and Phytomonas serpens and evaluated their potential as immunogens capable of inducing cross-protection against T. cruzi infection. Isolated EVs were characterized by Nanoparticle Tracking Analysis (NTA) and electron microscopy. A comparative proteomic analysis of EVs was performed using Mass Spectrometry-Based Proteomic Analysis (LC-MS/MS). The effects of EVs on immunomodulation and T. cruzi infection were assessed through in vitro and in vivo assays, using peripheral blood mononuclear cells (PBMCs) and BALB/c mice. The proteomic analysis identified shared proteins between the EVs of T. rangeli, P. serpens, and T. cruzi, including immunogenic candidates such as calpain-like cysteine peptidase and elongation factor 2. In vitro, pre-stimulation with the T. rangeli EVs reduced infection rates of the host cells by T. cruzi. In vivo, immunization with the EVs from T. rangeli and P. serpens led to a significant reduction in parasitemia in the BALB/c mice challenged with T. cruzi, though this did not translate into improved survival compared to controls. Interestingly, the EVs from T. cruzi also reduced parasitemia but did not confer protection against mortality. These findings suggest that while non-pathogenic trypanosomatid EVs exhibit potential immunogenic properties and can reduce parasitic load, their efficacy in preventing disease progression remains limited. Further research is needed to explore the mechanisms underlying these effects and to optimize EV-based strategies for protective immunity against Chagas disease. Full article
(This article belongs to the Special Issue Exosomes and Extracellular Vesicles in Health and Diseases: 3rd Edition)
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21 pages, 6805 KiB  
Article
Evaluation of the Anti-Cancer Potential of Extracellular Vesicles Derived from Human Amniotic Fluid Stem Cells: Focus on Effective miRNAs in the Treatment of Melanoma Progression
by Martina Gatti, Francesca Beretti, Gloria Ravegnini, Francesca Gorini, Eleonora Ceneri, Emma Bertucci, Matilde Y. Follo and Tullia Maraldi
Int. J. Mol. Sci. 2024, 25(23), 12502; https://doi.org/10.3390/ijms252312502 - 21 Nov 2024
Cited by 1 | Viewed by 1164
Abstract
Mesenchymal stromal cells (MSCs) and their secretome show intrinsic antitumor properties, however, the anti-cancer effects of MSCs remain debated and depend on the cancer type or model. MSCs derived from discarded samples, such as human amniotic fluid (hAFSC), have been introduced as an [...] Read more.
Mesenchymal stromal cells (MSCs) and their secretome show intrinsic antitumor properties, however, the anti-cancer effects of MSCs remain debated and depend on the cancer type or model. MSCs derived from discarded samples, such as human amniotic fluid (hAFSC), have been introduced as an attractive and potent stem cell source for clinical applications due to their collection procedures, which minimize ethical issues. Until now, various studies have obtained controversial results and poor understanding of the mechanisms behind the effects of perinatal cells on cancer cells. To better clarify this aspect, protein and miRNA expression profiling isolated from Extracellular vesicles (EVs) secreted by hAFSCs, obtained in the II or III trimester, were evaluated. Bioinformatic analysis was performed aiming at evaluating differential expression, pathway enrichment, and miRNA-mRNA networks. We highlighted that most of the highest expressed proteins and miRNAs are mainly involved in antioxidant and anti-cancer effects. Indeed, in the presence of hAFSC-EVs, a reduction of the G2/M phase was observed on melanoma cell lines, an activation of the apoptotic pathway occurred and the migration and invasion ability reduced. Our data demonstrated that II or III trimester hAFSCs can release bioactive factors into EVs, causing an efficient anti-cancer effect inhibiting melanoma progression. Full article
(This article belongs to the Special Issue Exosomes and Extracellular Vesicles in Health and Diseases: 3rd Edition)
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Review

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19 pages, 1704 KiB  
Review
Harnessing Mammalian- and Plant-Derived Exosomes for Drug Delivery: A Comparative Review
by Shynggys Sergazy, Sergazy Adekenov, Ilya Khabarov, Kymbat Adekenova, Assiya Maikenova and Mohamad Aljofan
Int. J. Mol. Sci. 2025, 26(10), 4857; https://doi.org/10.3390/ijms26104857 - 19 May 2025
Viewed by 133
Abstract
Exosomes, nanoscale vesicles involved in intercellular communication, have garnered significant attention for their potential in drug delivery and therapeutic applications. This review provides a comparative analysis of mammalian-derived exosomes, particularly milk-derived exosomes, and plant-derived exosome-like nanoparticles (PDENs). It explores their biogenesis, bioactivities, and [...] Read more.
Exosomes, nanoscale vesicles involved in intercellular communication, have garnered significant attention for their potential in drug delivery and therapeutic applications. This review provides a comparative analysis of mammalian-derived exosomes, particularly milk-derived exosomes, and plant-derived exosome-like nanoparticles (PDENs). It explores their biogenesis, bioactivities, and functional similarities, including their roles in cellular communication, immune modulation, and disease therapy. While milk-derived exosomes exhibit promising biocompatibility and stability for targeted delivery, PDENs offer distinct advantages, such as scalability and inherent bioactivities, derived from their plant sources. Despite similarities in their structure and cargo, PDENs differ in lipid composition and protein profiles, reflecting plant-specific functions. Emerging research highlights the therapeutic potential of PDENs in managing inflammation, oxidative stress, and other diseases, emphasizing their utility as functional food components and nanocarriers. However, challenges related to their chemical stability and large-scale production require further investigation. This review underscores the need for advanced studies to fully harness the potential of these natural nanocarriers in drug-delivery systems and therapeutic interventions. Full article
(This article belongs to the Special Issue Exosomes and Extracellular Vesicles in Health and Diseases: 3rd Edition)
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16 pages, 730 KiB  
Review
Extracellular Vesicles as a Potential Therapy for Stroke
by Ye Sun, Gui Wan and Xinjie Bao
Int. J. Mol. Sci. 2025, 26(7), 3130; https://doi.org/10.3390/ijms26073130 - 28 Mar 2025
Viewed by 591
Abstract
Although thrombolytic therapy has enjoyed relative success, limitations remain, such as a narrow therapeutic window and inconsistent efficacy. Consequently, there is a pressing need to develop novel therapeutic approaches. In recent years, extracellular vesicles (EVs) have garnered increasing attention as a potential alternative [...] Read more.
Although thrombolytic therapy has enjoyed relative success, limitations remain, such as a narrow therapeutic window and inconsistent efficacy. Consequently, there is a pressing need to develop novel therapeutic approaches. In recent years, extracellular vesicles (EVs) have garnered increasing attention as a potential alternative to stem cell therapy. Because of their ability to cross the blood–brain barrier and exert neuroprotective effects in cerebral ischemia and hemorrhage, the exploration of EVs for clinical application in stroke treatment is expanding. EVs are characterized by high heterogeneity, with their composition closely mirroring that of their parent cells. This property enables EVs to distinguish between cerebral ischemia and hemorrhage, thus facilitating a more rapid and accurate diagnosis. Additionally, EVs can be engineered to carry specific molecules, such as miRNAs, targeting them to specific cells, potentially enhancing the therapeutic outcome and improving stroke prognosis. In this review, we will also explore the methodologies for the isolation and extraction of EVs, critically evaluating the advantages and disadvantages of various commonly employed separation techniques. Furthermore, we will briefly address current EV preservation and administration methods, providing a comprehensive overview of the state of EV-based therapies in stroke treatment. Full article
(This article belongs to the Special Issue Exosomes and Extracellular Vesicles in Health and Diseases: 3rd Edition)
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30 pages, 911 KiB  
Review
Therapeutic Efficacy and Promise of Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in Aging and Age-Related Disorders
by Anyuan Zhang, Qiubai Li and Zhichao Chen
Int. J. Mol. Sci. 2025, 26(1), 225; https://doi.org/10.3390/ijms26010225 - 30 Dec 2024
Cited by 3 | Viewed by 1950
Abstract
The global issue of aging populations has become increasingly prominent, thus the research and development for anti-aging therapies to assure longevity as well as to ameliorate age-related complications is put high on the agenda. The young humoral milieu has been substantiated to impart [...] Read more.
The global issue of aging populations has become increasingly prominent, thus the research and development for anti-aging therapies to assure longevity as well as to ameliorate age-related complications is put high on the agenda. The young humoral milieu has been substantiated to impart youthful characteristics to aged cells or organs. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membrane-limited structures that serve as couriers of proteins and genetic material to regulate intercellular communication. Of note, EVs appeared to be an indispensable component of young blood in prolonging lifespans, and circulating EVs have been indicated to mediate the beneficial effect of a young milieu on aging. Human umbilical cord mesenchymal stem cell-derived EVs (HUCMSC-EVs), isolated from the youngest adult stem cell source, are speculated to reproduce the function of circulating EVs in young blood and partially revitalize numerous organs in old animals. Robust evidence has suggested HUCMSC-EVs as muti-target therapeutic agents in combating aging and alleviating age-related degenerative disorders. Here, we provide a comprehensive overview of the anti-aging effects of HUCMSC-EVs in brain, heart, vasculature, kidney, muscle, bone, and other organs. Furthermore, we critically discuss the current investigation on engineering strategies of HUCMSC-EVs, intending to unveil their full potential in the field of anti-aging research. Full article
(This article belongs to the Special Issue Exosomes and Extracellular Vesicles in Health and Diseases: 3rd Edition)
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30 pages, 4672 KiB  
Review
Glioma-Derived Exosomes and Their Application as Drug Nanoparticles
by Serena Mastantuono, Ivana Manini, Carla Di Loreto, Antonio Paolo Beltrami, Marco Vindigni and Daniela Cesselli
Int. J. Mol. Sci. 2024, 25(23), 12524; https://doi.org/10.3390/ijms252312524 - 21 Nov 2024
Cited by 1 | Viewed by 1232
Abstract
Glioblastoma Multiforme (GBM) is the most aggressive primary tumor of the Central Nervous System (CNS) with a low survival rate. The malignancy of GBM is sustained by a bidirectional crosstalk between tumor cells and the Tumor Microenvironment (TME). This mechanism of intercellular communication [...] Read more.
Glioblastoma Multiforme (GBM) is the most aggressive primary tumor of the Central Nervous System (CNS) with a low survival rate. The malignancy of GBM is sustained by a bidirectional crosstalk between tumor cells and the Tumor Microenvironment (TME). This mechanism of intercellular communication is mediated, at least in part, by the release of exosomes. Glioma-Derived Exosomes (GDEs) work, indeed, as potent signaling particles promoting the progression of brain tumors by inducing tumor proliferation, invasion, migration, angiogenesis and resistance to chemotherapy or radiation. Given their nanoscale size, exosomes can cross the blood–brain barrier (BBB), thus becoming not only a promising biomarker to predict diagnosis and prognosis but also a therapeutic target to treat GBM. In this review, we describe the structural and functional characteristics of exosomes and their involvement in GBM development, diagnosis, prognosis and treatment. In addition, we discuss how exosomes can be modified to be used as a therapeutic target/drug delivery system for clinical applications. Full article
(This article belongs to the Special Issue Exosomes and Extracellular Vesicles in Health and Diseases: 3rd Edition)
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