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The Role of Extracellular Vesicles in Inflammatory Diseases
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The Role of Extracellular Vesicles in Inflammatory Diseases

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: 20 August 2025 | Viewed by 1865

Special Issue Editor

Dr. Kaushik Das

E-Mail Website
Guest Editor
Department of Cellular and Molecular Biology, The University of Texas at Tyler Health Science Center, Tyler, TX 75708, USA
Interests: extracellular vesicles; microRNAs; inflammation; blood coagulation; hemophilia; thrombocytopenia; sepsis; cancer; breast cancer; lung cancer; metastasis; angiogenesis; cancer therapy; drug delivery; cell signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) are nano-sized bodies, secreted by cells into the extracellular environment. In the past, EVs were considered 'cellular dust'; however, a growing body of evidence indicates that EVs are an important contributor in various diseased conditions. Over the past few decades, EVs have been shown to influence various inflammatory diseased conditions via the transfer of their cargo in the form of nucleic acids, proteins, lipids, metabolites, etc., between cells. The present Special Issue focuses on how EVs contribute to the pathogenesis of inflammatory diseases. EV application in therapeutic agents for inflammation-associated diseases will also be covered in the present Special Issue.

Dr. Kaushik Das
Guest Editor

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Keywords

  • extracellular vesicles
  • inflammation
  • inflammatory diseases
  • pathogenesis

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Published Papers (4 papers)

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Research

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18 pages, 3743 KiB  
Article
Effect of Small Extracellular Vesicles Produced by Mesenchymal Stem Cells on 5xFAD Mice Hippocampal Cultures
by Daria Y. Zhdanova, Natalia V. Bobkova, Alina V. Chaplygina, Elena V. Svirshchevskaya, Rimma A. Poltavtseva, Anastasia A. Vodennikova, Vasiliy S. Chernyshev and Gennadiy T. Sukhikh
Int. J. Mol. Sci. 2025, 26(9), 4026; https://doi.org/10.3390/ijms26094026 - 24 Apr 2025
Abstract
Alzheimer’s disease (AD) is one of the most common progressive neurodegenerative diseases leading to impairments in memory, orientation, and behavior. However, significant work is still needed to fully understand the progression of such disease and develop novel therapeutic agents for AD prevention and [...] Read more.
Alzheimer’s disease (AD) is one of the most common progressive neurodegenerative diseases leading to impairments in memory, orientation, and behavior. However, significant work is still needed to fully understand the progression of such disease and develop novel therapeutic agents for AD prevention and treatment. Small extracellular vesicles (sEVs) have received attention in recent years due to their potential therapeutic effects on AD. The aim of this study was to determine the potential effect of sEVs in an in vitro model of AD. sEVs were isolated from human Wharton’s jelly mesenchymal stem cells (MSCs) by asymmetric depth filtration, a method developed recently by us. AD was modeled in vitro using cells obtained from the hippocampi of newborn 5xFAD transgenic mice carrying mutations involved in familial AD. After isolation, sEVs underwent detailed characterization that included scanning electron microscopy, nanoparticle tracking analysis, confocal microscopy, Western blotting, and Luminex assay. When added to 5xFAD hippocampal cells, sEVs were nontoxic, colocalized with neurons and astrocytes, decreased the level of Aβ peptide, and increased the synaptic density. These results support the possibility that sEVs can improve brain cell function during aging, decrease the risk of AD, and potentially be used for AD therapeutics. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Inflammatory Diseases)
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9 pages, 1266 KiB  
Article
Lymphomonocytic Extracellular Vesicles Influence Fibroblast Proliferation and Collagen Production in Systemic Sclerosis
by Giuseppe Argentino, Bianca Olivieri, Matteo Morandi, Giulio Bonisoli, Ruggero Beri, Elisa Tinazzi and Simonetta Friso
Int. J. Mol. Sci. 2025, 26(6), 2699; https://doi.org/10.3390/ijms26062699 - 17 Mar 2025
Viewed by 348
Abstract
Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by fibrosis, immune dysregulation, and vascular abnormalities. Extracellular vesicles (EVs), secreted by immune cells, have been implicated in modulating fibroblast activity and are actively involved in SSc pathogenesis. This study aims to determine whether [...] Read more.
Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by fibrosis, immune dysregulation, and vascular abnormalities. Extracellular vesicles (EVs), secreted by immune cells, have been implicated in modulating fibroblast activity and are actively involved in SSc pathogenesis. This study aims to determine whether lymphomonocytic-derived EVs influence fibroblast proliferation and collagen synthesis in SSc. Fibroblasts from healthy donors (HDFs) and SSc patients (SScHDFs) were exposed to EVs derived from Jurkat and U937 cell lines stimulated under pro-inflammatory conditions using tumor necrosis factor-α (TNFα) or phorbol 12-myristate 13-acetate + ionomycin (PMA + IONO). Proliferation was assessed using CCK-8 assays, while collagen production was quantified via ELISA. Our findings demonstrate that EVs derived from PMA + IONO-stimulated Jurkat and U937 cells significantly reduced fibroblast proliferation in a dose-dependent manner. Notably, SScHDFs exhibited lower baseline proliferation and a diminished overall response to EV treatment. Collagen production was markedly reduced in both fibroblast types following exposure to PMA + IONO-stimulated EVs, whereas TNFα-stimulated EVs affected only HDFs. These findings suggest that EVs from activated immune cells modulate fibroblast function in SSc, potentially contributing to disease pathogenesis. Further research is warranted to elucidate the molecular mechanisms underlying these effects and to explore the therapeutic potential of targeting EV-mediated signaling in SSc. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Inflammatory Diseases)
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Review

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26 pages, 1211 KiB  
Review
Therapeutic Potential of Extracellular Vesicles in Oral Inflammation
by Yan Rou Farm, Bing Huan Chuah, Jia Xian Law, Xin Fang Leong, Masfueh Razali and Sook Luan Ng
Int. J. Mol. Sci. 2025, 26(7), 3031; https://doi.org/10.3390/ijms26073031 - 26 Mar 2025
Viewed by 382
Abstract
The therapeutic potential of extracellular vesicles (EVs) in reducing oral inflammation is thoroughly examined in this review, with an emphasis on gingivitis, periodontitis, and oral mucositis. It explains the complex relationship between microbial dysbiosis and host immune responses in the aetiology of oral [...] Read more.
The therapeutic potential of extracellular vesicles (EVs) in reducing oral inflammation is thoroughly examined in this review, with an emphasis on gingivitis, periodontitis, and oral mucositis. It explains the complex relationship between microbial dysbiosis and host immune responses in the aetiology of oral inflammation. Pathophysiological mechanisms of periodontitis are examined, emphasising the roles played by periodontal pathogens and inflammatory mediators in the disease’s chronic course and systemic effects. Preclinical research is providing new evidence that EVs originating from various cellular sources control immune cell dynamics towards a pro-healing phenotype, promote tissue regeneration, and have immunomodulatory qualities. EV-based therapies appear to be a promising new therapeutic technique with potential benefits over traditional methods for the treatment of oral inflammatory illnesses by specifically altering inflammatory signalling pathways. This review highlights the potential of EVs to improve patient outcomes in oral health and emphasises the need for additional clinical research to clarify the therapeutic efficacy and underlying mechanisms of EVs in periodontal therapy. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Inflammatory Diseases)
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17 pages, 1414 KiB  
Review
Extracellular Vesicles in the Mesenchymal Stem Cell/Macrophage Axis: Potential Targets for Inflammatory Treatment
by Zhen Che, Wenbin Yan and Qun Zhao
Int. J. Mol. Sci. 2025, 26(6), 2827; https://doi.org/10.3390/ijms26062827 - 20 Mar 2025
Viewed by 523
Abstract
Mesenchymal stem cells (MSCs) have been widely used for the treatment of autoimmune and inflammatory diseases due to their pluripotent differentiation potential and immunomodulatory function. Macrophage (Mφ) polarization also acts an essential and central role in regulating inflammation, basically the dynamic balance of [...] Read more.
Mesenchymal stem cells (MSCs) have been widely used for the treatment of autoimmune and inflammatory diseases due to their pluripotent differentiation potential and immunomodulatory function. Macrophage (Mφ) polarization also acts an essential and central role in regulating inflammation, basically the dynamic balance of pro-inflammatory M1-like (M1φ) and anti-inflammatory M2-like macrophages (M2φ), affecting the occurrence and progression of inflammatory diseases. Since a pivotal molecular crosstalk between MSCs and Mφ has been elucidated using in vitro and in vivo preclinical studies, we presume that the mesenchymal stem cell/macrophages axis (MSC/Mφ axis) acts an important role in pathophysiological mechanisms of inflammatory diseases and should be the potential therapeutic target. However, the crucial effects of EVs as intercellular communicators and therapeutic agents in the MSC/Mφ axis remains explorable. Therefore, this review elaborated on the mechanisms of EVs mediating the MSC/Mφ axis regulating inflammation in-depth, hoping to provide more references for related research in the future. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Inflammatory Diseases)
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