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Cutting-Edge Research and Applications of Extracellular Microvesicles in Disease Management

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Guest Editor
Department of Experimental Biology, Faculty of Health Sciences, University of Jaén, 23071 Jaén, Spain
Interests: celiac disease; intestinal organoids; extracellular microvesicles in liquid biopsy; immune checkpoints
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Special Issue Information

Dear Colleagues,

Research on extracellular microvesicles (EMVs) at the molecular level is a rapidly advancing field with transformative implications for disease management. EMVs, derived from cells, act as essential mediators in intercellular communication, transporting a diverse array of bioactive molecules. The cargoes of extracellular microvesicles reflect core intracellular processes, and their functional properties may regulate fundamental biological and pathological processes. Their composition, reflecting the physiological state of parent cells, holds significant value for diagnostics and therapies.  In cancer, EMVs stand out as promising biomarkers for early detection and treatment monitoring. Furthermore, their exploration in immune modulation holds potential for treating autoimmune diseases. The capability of EMVs to traverse biological barriers, including the blood–brain barrier, provides opportunities for targeted drug delivery in neurological disorders. In developmental biology, EMVs influence signaling pathways, cell differentiation, and the coordination of developmental events, offering insights into regenerative medicine.

This Special Issue of the International Journal of Molecular Sciences focuses on the molecular research and applications of extracellular microvesicles in disease management, welcoming both original research articles and reviews that address the perspective of highly targeted and personalized therapies, marking a paradigm shift in disease management.

Dr. María Isabel Torres
Guest Editor

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Keywords

  • extraccellular microvesicles
  • exosome
  • ectosoma
  • biomarkers
  • cargoes of extracellular vesicles
  • therapeutics
  • diagnosis

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Published Papers (5 papers)

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Research

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15 pages, 4103 KiB  
Article
Simultaneous Detection of Collagen I Alpha II and Cytokeratin 19 mRNA by Multiplex qPCR in Liquid Biopsy in Diagnosis of Patients with Resectable Solid Tumors
by Lara Sofía Estévez Pérez, Begoña O. Alén, María Otero Alén, Saioa Domínguez Hormaetxe, Laureano Simón and Ángel Concha
Int. J. Mol. Sci. 2024, 25(17), 9567; https://doi.org/10.3390/ijms25179567 - 3 Sep 2024
Viewed by 1037
Abstract
The early detection of tumors is one of the key factors in increasing overall survival in cancer patients. A wide range of cancers still do not have a system of early diagnosis; therefore, the development of new non-invasive tools in this line is [...] Read more.
The early detection of tumors is one of the key factors in increasing overall survival in cancer patients. A wide range of cancers still do not have a system of early diagnosis; therefore, the development of new non-invasive tools in this line is essential. Accordingly, the objective of our work was to develop a non-invasive screening method for the early detection of various carcinomas in plasma using a panel that combines two markers using RT-qPCR. A retrospective case-control study was conducted to develop a cancer screening test based on the detection of stromal and epithelial biomarkers (COL1A2 and KRT19) in plasma. The expression of biomarkers was evaluated using multiplex quantitative PCR applied to 47 cases with non-metastatic tumors and 13 control participants. For both biomarkers, a cut-off value was stablished using Youden’s J index through ROC curve analysis and areas under the curve (AUC) were calculated. The plasma mRNA expression level of both biomarkers was significantly higher in diseased versus healthy patients. Moreover, ROC curve analysis showed an AUC value of 0.897 for the combined model. This model also resulted in a cutoff value of 0.664, as well as a sensitivity of 83% and a specificity of 84.6%. These results suggest that the plasma expression levels of COL1A2 and KRT19 could a have potential role in detecting various types of cancer at the early stages. The combined analysis of both stromal and epithelial biomarkers would provide a non-invasive screening method that would allow us to differentiate patients with an active neoplastic process. Full article
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17 pages, 2705 KiB  
Article
The Exosomes of Stem Cells from Human Exfoliated Deciduous Teeth Suppress Inflammation in Osteoarthritis
by Chuang-Yu Lin, Parichart Naruphontjirakul, Te-Yang Huang, Yi-Chia Wu, Wei-Hsuan Cheng and Wen-Ta Su
Int. J. Mol. Sci. 2024, 25(16), 8560; https://doi.org/10.3390/ijms25168560 - 6 Aug 2024
Viewed by 1585
Abstract
Hyaluronic acid injection is commonly used clinically to slow down the development of osteoarthritis (OA). A newly developed therapeutic method is to implant chondrocytes/stem cells to regenerate cartilage in the body. The curative effect of stem cell therapy has been proven to come [...] Read more.
Hyaluronic acid injection is commonly used clinically to slow down the development of osteoarthritis (OA). A newly developed therapeutic method is to implant chondrocytes/stem cells to regenerate cartilage in the body. The curative effect of stem cell therapy has been proven to come from the paracrine of stem cells. In this study, exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED) and hyaluronic acid were used individually to evaluate the therapeutic effect in slowing down OA. SHED was cultured in a serum-free medium for three days, and the supernatant was collected and then centrifuged with a speed difference to obtain exosomes containing CD9 and CD63 markers, with an average particle size of 154.1 nm. SW1353 cells were stimulated with IL-1β to produce the inflammatory characteristics of OA and then treated with 40 μg/mL exosomes and hyaluronic acid individually. The results showed that the exosomes successfully inhibited the pro-inflammatory factors, including TNF-α, IL-6, iNOS, NO, COX-2 and PGE2, induced by IL-1β and the degrading enzyme of the extrachondral matrix (MMP-13). Collagen II and ACAN, the main components of the extrachondral matrix, were also increased by 1.76-fold and 2.98-fold, respectively, after treatment, which were similar to that of the normal joints. The effect can be attributed to the partial mediation of SHED exosomes to the NF-κB pathway, and the ability of exosomes to inhibit OA is found not inferior to that of hyaluronic acid. Full article
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11 pages, 2048 KiB  
Article
Unveiling the Cutting-Edge Impact of Polarized Macrophage-Derived Extracellular Vesicles and MiRNA Signatures on TGF-β Regulation within Lung Fibroblasts
by Alvise Casara, Maria Conti, Nicol Bernardinello, Mariaenrica Tinè, Simonetta Baraldo, Graziella Turato, Umberto Semenzato, Alessandro Celi, Paolo Spagnolo, Marina Saetta, Manuel G. Cosio, Tommaso Neri, Davide Biondini and Erica Bazzan
Int. J. Mol. Sci. 2024, 25(13), 7490; https://doi.org/10.3390/ijms25137490 - 8 Jul 2024
Cited by 1 | Viewed by 1290
Abstract
Depending on local cues, macrophages can polarize into classically activated (M1) or alternatively activated (M2) phenotypes. This study investigates the impact of polarized macrophage-derived Extracellular Vesicles (EVs) (M1 and M2) and their cargo of miRNA-19a-3p and miRNA-425-5p on TGF-β production in lung fibroblasts. [...] Read more.
Depending on local cues, macrophages can polarize into classically activated (M1) or alternatively activated (M2) phenotypes. This study investigates the impact of polarized macrophage-derived Extracellular Vesicles (EVs) (M1 and M2) and their cargo of miRNA-19a-3p and miRNA-425-5p on TGF-β production in lung fibroblasts. EVs were isolated from supernatants of M0, M1, and M2 macrophages and quantified using nanoscale flow cytometry prior to fibroblast stimulation. The concentration of TGF-β in fibroblast supernatants was measured using ELISA assays. The expression levels of miRNA-19a-3p and miRNA-425-5p were assessed via TaqMan-qPCR. TGF-β production after stimulation with M0-derived EVs and with M1-derived EVs increased significantly compared to untreated fibroblasts. miRNA-425-5p, but not miRNA-19a-3p, was significantly upregulated in M2-derived EVs compared to M0- and M1-derived EVs. This study demonstrates that EVs derived from both M0 and M1 polarized macrophages induce the production of TGF-β in fibroblasts, with potential regulation by miRNA-425-5p. Full article
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Review

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40 pages, 2631 KiB  
Review
Extracellular Vesicles: Advanced Tools for Disease Diagnosis, Monitoring, and Therapies
by Pedro Lorite, Jorge N. Domínguez, Teresa Palomeque and María Isabel Torres
Int. J. Mol. Sci. 2025, 26(1), 189; https://doi.org/10.3390/ijms26010189 - 29 Dec 2024
Cited by 3 | Viewed by 1805
Abstract
Extracellular vesicles (EVs) are a heterogeneous group of membrane-encapsulated vesicles released by cells into the extracellular space. They play a crucial role in intercellular communication by transporting bioactive molecules such as proteins, lipids, and nucleic acids. EVs can be detected in body fluids, [...] Read more.
Extracellular vesicles (EVs) are a heterogeneous group of membrane-encapsulated vesicles released by cells into the extracellular space. They play a crucial role in intercellular communication by transporting bioactive molecules such as proteins, lipids, and nucleic acids. EVs can be detected in body fluids, including blood plasma, urine, saliva, amniotic fluid, breast milk, and pleural ascites. The complexity and diversity of EVs require a robust and standardized approach. By adhering to standardized protocols and guidelines, researchers can ensure the consistency, purity, and reproducibility of isolated EVs, facilitating their use in diagnostics, therapies, and research. Exosomes and microvesicles represent an exciting frontier in modern medicine, with significant potential to transform the diagnosis and treatment of various diseases with an important role in personalized medicine and precision therapy. The primary objective of this review is to provide an updated analysis of the significance of EVs by highlighting their mechanisms of action and exploring their applications in the diagnosis and treatment of various diseases. Additionally, the review addresses the existing limitations and future potential of EVs, offering practical recommendations to resolve current challenges and enhance their viability for clinical use. This comprehensive approach aims to bridge the gap between EV research and its practical application in healthcare. Full article
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20 pages, 2382 KiB  
Review
Functions and Clinical Applications of Extracellular Vesicles in TH2 Cell-Mediated Airway Inflammatory Diseases: A Review
by Jaehwan Cheon, Byoungjae Kim, Juhyun Lee, Jaemin Shin and Tae Hoon Kim
Int. J. Mol. Sci. 2024, 25(17), 9455; https://doi.org/10.3390/ijms25179455 - 30 Aug 2024
Cited by 2 | Viewed by 1325
Abstract
Type 2 airway inflammation (T2AI), driven by type 2 innate lymphoid and CD4+ T helper 2 cells, leads to various diseases and conditions, such as chronic rhinosinusitis with nasal polyps, allergic rhinitis, and asthma. Emerging evidence suggests the involvement of extracellular vesicles [...] Read more.
Type 2 airway inflammation (T2AI), driven by type 2 innate lymphoid and CD4+ T helper 2 cells, leads to various diseases and conditions, such as chronic rhinosinusitis with nasal polyps, allergic rhinitis, and asthma. Emerging evidence suggests the involvement of extracellular vesicles (EVs) in these diseases. In this review, we describe the immunological T2AI pathogenic mechanisms, outline EV characteristics, and highlight their applications in the diagnosis and treatment of T2AI. An extensive literature search was conducted using appropriate strategies to identify relevant articles from various online databases. EVs in various biological samples showed disease-specific characteristics for chronic rhinosinusitis with nasal polyps, allergic rhinitis, and asthma, with some demonstrating therapeutic effects against these conditions. However, most studies have been limited to in vitro and animal models, highlighting the need for further clinical research on the diagnostic and therapeutic applications of EVs. Full article
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