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Current Insights into the Role of Exosomes in Intercellular Communication, 2nd Edition

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

Deadline for manuscript submissions: 31 December 2026 | Viewed by 3658

Special Issue Editor

Dr. Orit Uziel

E-Mail Website
Guest Editor
1. The Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva 49100, Israel
2. The Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv 69978, Israel
3. Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva 49100, Israel
Interests: telomeres; telomerase; cancer research; exosomes; microenvironment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Exosomes are extracellular vesicles (EVs) ranging in diameter from 30 to 150 nm. Formed by the endosomal membrane, they are practically secreted from all types of cells and cell microenvironments. In the human body, they travel in bodily liquids, such as blood, saliva, and urine. Exosomes contain thousands of molecules, including nucleic acids of all types, proteins, and lipids, reflecting the molecular makeup of their cells of origin. Upon travelling in bodily liquids, they may be engulfed by other recipient cells, where they release their cargo. Since part of the molecular cargo is biologically active, it may interfere with the host cells’ signal transduction pathways upon their cellular integration. Therefore, exosomes are considered mediators of cell–cell communications. As such, their roles in numerous biological activities are continuously being reported.

For this Special Issue of IJMS, we are gathering manuscripts focusing on the various roles of exosomes in cell–cell communications in all biological systems.

Dr. Orit Uziel
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 250 words) can be sent to the Editorial Office for assessment.

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

  • exosomes
  • extracellular vesicles
  • intracellular communication
  • intercellular communication

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Published Papers (5 papers)

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Research

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19 pages, 89538 KB  
Article
Chronic Lymphocytic Leukemia (CLL)-Derived Extracellular Vesicles (EVs) Modulate Monocytes to Become CLL-Supportive Cells
by Shaked Noah, Einat Be’ery, Zinab Sarsor, Aladin Samara, Pia Raanani and Orit Uziel
Int. J. Mol. Sci. 2026, 27(10), 4638; https://doi.org/10.3390/ijms27104638 - 21 May 2026
Viewed by 398
Abstract
In light of our previous publication, we hypothesized that chronic lymphocytic leukemia (CLL) cells also recruit monocytes to acquire survival advantage. To test this, we treated Buffy coat-driven monocytes with exosomes isolated from the peripheral blood of 45 treatment-naïve patients. The CLL-derived exosomes [...] Read more.
In light of our previous publication, we hypothesized that chronic lymphocytic leukemia (CLL) cells also recruit monocytes to acquire survival advantage. To test this, we treated Buffy coat-driven monocytes with exosomes isolated from the peripheral blood of 45 treatment-naïve patients. The CLL-derived exosomes turned monocytes into IL-6-producing cells as an increase of 13-fold in the IL-6 levels was obtained in the growth medium of the exposed monocytes. Subsequently, we filtered out the monocytes and added CLL cells to this IL-6 enriched medium. As a result, the oncogene STAT3 became phosphorylated, and thus may have provided the cells with a survival advantage. A total of 67 phosphoproteins were upregulated in response to CLL-derived exosomal exposure in the recipient monocytes, with TFIIF being among the top scored proteins in this analysis. Transfection of monocytes with a TFIIF-containing vector increased the levels of IL-6 about 14-fold in the culture medium. Importantly, the CLL-derived exosomes induced the transformation of a portion of the recipient monocytes (45% compared to 30% of the unexposed cells) to become nurse-like fibrocyte cells. Taken together, CLL cells communicate with monocytes through the exosomes that they release. Once they are taken up by monocytes, they turn them into IL-6-producing cells, which provide a survival advantage to the neoplastic cells, creating a vicious circle that promotes disease progression. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication, 2nd Edition)
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30 pages, 41784 KB  
Article
Small Extracellular Vesicle Release Following Electrical Pulse Stimulation of C2C12 Myotubes: Effects on microRNA Cargo and Myoblast Migration and Differentiation
by John S. Hingle, Rhys S. McColl, Ivan J. Vechetti and Kathryn H. Myburgh
Int. J. Mol. Sci. 2026, 27(10), 4320; https://doi.org/10.3390/ijms27104320 - 12 May 2026
Viewed by 442
Abstract
The skeletal muscle (SkM) secretome has been widely studied since the establishment of its endocrine function. Extracellular vesicles (EVs) are the most recently identified elements of the SkM secretome. These nano-sized lipid-bound vesicles carry molecular cargo and function as a means of intercellular [...] Read more.
The skeletal muscle (SkM) secretome has been widely studied since the establishment of its endocrine function. Extracellular vesicles (EVs) are the most recently identified elements of the SkM secretome. These nano-sized lipid-bound vesicles carry molecular cargo and function as a means of intercellular communication. The effect of exercise on SkM EV micro-RNA cargo (miRNAs) remains a challenge to elucidate. Electrical pulse stimulation (EPS) was applied to C2C12 myotubes at high (30 Hz) and low (2 Hz) frequencies. EVs released during 10 h of stimulation were isolated and characterized and used to treat myoblasts. Their miRNA cargo was sequenced. EVs were used to treat myoblasts (2.19 × 108 EVs per mL) to determine the effects on myoblast migration and differentiation. Sequencing revealed over 300 known miRNAs packaged into myotube EVs. Many were differentially expressed after EPS, either positively or negatively. Muscle-important miRNAs were present (miR-206 was 4.8-fold more prevalent than any other miRNA). EV treatments improved myoblast migration and differentiation without a frequency-specific influence. Gene Ontology analysis based on differentially expressed miRNAs between control and EPS-EVs indicates an effect of EPS frequency on muscle EV signaling. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication, 2nd Edition)
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17 pages, 11692 KB  
Article
Modulation of ESKAPE Bacteria Properties by NK-92 and NK-92-Derived LEVs: First Insights
by Polina Grebenkina, Elizaveta Tyshchuk, Ananstasia Gulina, Maria Nyukalova, Vladimir Zarubaev, Natalia Arsentieva, Areg Totolian, Lyudmila Kraeva and Dmitry Sokolov
Int. J. Mol. Sci. 2026, 27(9), 3953; https://doi.org/10.3390/ijms27093953 - 29 Apr 2026
Viewed by 445
Abstract
ESKAPE pathogens represent a critical threat to global health. This challenge necessitates the development of novel antibacterial strategies. We investigated the antimicrobial potential of NK-92 cells and their derived large extracellular vesicles using flow cytometry, ELISA, confocal microscopy and microbiology assays. Here, we [...] Read more.
ESKAPE pathogens represent a critical threat to global health. This challenge necessitates the development of novel antibacterial strategies. We investigated the antimicrobial potential of NK-92 cells and their derived large extracellular vesicles using flow cytometry, ELISA, confocal microscopy and microbiology assays. Here, we show that both NK-92 cells and NK-92-derived LEVs can interact with bacteria, as confirmed by confocal microscopy and flow cytometry. This interaction is associated with inhibition of colony formation. A possible mechanism can involve defensin-α1 secreted by NK-92 and packed in their LEVs. NK-92-derived LEVs can modulate S. aureus viability, colony growth and clindamycin susceptibility. These findings suggest NK cell-derived LEVs as promising strategies to combat multidrug-resistant bacterial infections. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication, 2nd Edition)
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Review

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24 pages, 1739 KB  
Review
Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions
by Eman Salem Algariri, Fazlina Nordin, Min Hwei Ng, Izyan Mohd Idris, Norwahidah Abdul Karim, Gee Jun Tye and Wan Safwani Wan Kamarul Zaman
Int. J. Mol. Sci. 2026, 27(4), 1981; https://doi.org/10.3390/ijms27041981 - 19 Feb 2026
Cited by 2 | Viewed by 805
Abstract
Mitochondrial dysfunction is a central pathological feature of a wide range of inherited and acquired disorders and is characterized by impaired oxidative phosphorylation, disrupted cellular energy metabolism, and excessive oxidative stress. Although advances in molecular diagnostics have improved disease recognition, effective disease-modifying therapies [...] Read more.
Mitochondrial dysfunction is a central pathological feature of a wide range of inherited and acquired disorders and is characterized by impaired oxidative phosphorylation, disrupted cellular energy metabolism, and excessive oxidative stress. Although advances in molecular diagnostics have improved disease recognition, effective disease-modifying therapies remain limited, and clinical outcomes are often suboptimal, highlighting the need for novel therapeutic strategies. Mesenchymal stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have emerged as promising candidates for targeting mitochondrial dysfunction due to their regenerative, immunomodulatory, and metabolic regulatory properties. In this review, we provide a comprehensive overview of recent in vitro and in vivo studies investigating the capacity of MSCs and MSC-EVs to restore mitochondrial function by enhancing mitochondrial respiration, improving cellular bioenergetics, and reducing oxidative stress across diverse disease models. We further discuss the underlying mechanisms involved, including mitochondrial transfer, delivery of functional mitochondrial components, and modulation of the cellular microenvironment. Finally, we highlight the key advantages, translational potential, and remaining challenges associated with MSC- and MSC-EV-based therapies for mitochondrial dysfunction. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication, 2nd Edition)
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32 pages, 1333 KB  
Review
Safety Assessment of Extracellular Vesicle-Based Therapy in Regenerative Dentistry
by Bing-Huan Chuah, Jia-Xian Law, Xin-Fang Leong, Kok-Lun Pang, Yan-Rou Farm, Masfueh Razali and Sook-Luan Ng
Int. J. Mol. Sci. 2026, 27(2), 798; https://doi.org/10.3390/ijms27020798 - 13 Jan 2026
Cited by 6 | Viewed by 1102
Abstract
Extracellular vesicle (EV)-based therapies have emerged as promising, cell-free approaches for dental tissue regeneration. This narrative review integrates mechanistic insights, therapeutic efficacy data, and safety and delivery considerations from in vitro and in vivo studies to elucidate the molecular mechanisms by which EVs, [...] Read more.
Extracellular vesicle (EV)-based therapies have emerged as promising, cell-free approaches for dental tissue regeneration. This narrative review integrates mechanistic insights, therapeutic efficacy data, and safety and delivery considerations from in vitro and in vivo studies to elucidate the molecular mechanisms by which EVs, particularly those from dental pulp stem cells (DPSCs) and mesenchymal stem cells (MSCs), drive regenerative processes via key signalling axes (PI3K/Akt, MAPK, BMP/Smad, and Hedgehog). Preclinical studies demonstrate that unmodified and engineered EVs enhance odontogenic differentiation, angiogenesis, bone repair, and immunomodulation in models of pulp regeneration, alveolar bone defects, osteonecrosis, and periodontitis. Isolation and purification methodologies were also evaluated, comparing ultracentrifugation, size-exclusion chromatography, and density-cushion approaches, and discussing how protocol variations affect EV purity, dosing metrics, and functional reproducibility. Early-phase clinical evaluations report only low-grade transient adverse events, underscoring a generally favourable safety profile. Despite these encouraging results, significant challenges remain: heterogeneity in EV cargo composition, lack of standardised potency assays, and incomplete long-term safety data. The review highlights the urgent need for rigorous, harmonised regulatory frameworks and robust quality control measures to ensure that EV-based modalities can be translated into safe, effective, and reproducible therapies in regenerative dentistry. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication, 2nd Edition)
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