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Current Insights into the Role of Exosomes in Intercellular Communication
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Current Insights into the Role of Exosomes in Intercellular Communication

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: 20 January 2025 | Viewed by 11867

Special Issue Editor

Dr. Orit Uziel

E-Mail Website
Guest Editor
Rabin Medical Center Israel, Petah Tiqwa, Israel
Interests: exosomes; microenvironment; telomeres; telomerase; hematological cancers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Exosomes are extracellular vesicles (EVs) ranging in diameter from 30 to 150nm. 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 including the blood, saliva, urine, etc. 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 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

  • exosomes
  • extravesicles
  • intracellular communication

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Published Papers (7 papers)

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Research

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19 pages, 2336 KiB  
Article
Prenatal Opioid and Alcohol Exposures: Association with Altered Placental Serotonin Transporter Structure and/or Expression
by Nune Darbinian, Nana Merabova, Gabriel Tatevosian, Sandra Adele, Armine Darbinyan, Mary F. Morrison, C. Lindsay DeVane, Sammanda Ramamoorthy, Laura Goetzl and Michael E. Selzer
Int. J. Mol. Sci. 2024, 25(21), 11570; https://doi.org/10.3390/ijms252111570 - 28 Oct 2024
Viewed by 604
Abstract
Fetal exposures to many drugs of abuse, e.g., opioids and alcohol (EtOH), are associated with adverse neurodevelopmental problems in early childhood, including abnormalities in activity of the serotonin (5HT) transporter (SERT), which transports 5HT across the placenta. Little is known about the effects [...] Read more.
Fetal exposures to many drugs of abuse, e.g., opioids and alcohol (EtOH), are associated with adverse neurodevelopmental problems in early childhood, including abnormalities in activity of the serotonin (5HT) transporter (SERT), which transports 5HT across the placenta. Little is known about the effects of these drugs on SERT expression. Pregnant women who used EtOH or opioids were compared to gestational age-matched controls using a structured questionnaire to determine prenatal substance exposure. Following elective pregnancy termination, placental membranous vesicles and exosomes were prepared from first and second trimester human placentas. Changes in EtOH- or opioid-exposed placental SERT expression and modifications were assessed by quantitative western blot. Novel SERT isoforms were sequenced and analyzed. Opioid-exposed but not EtOH-exposed maternal placentas showed SERT cleavage and formation of new SERT fragments (isoforms). Alcohol-exposed cases showed reduced SERT levels. Antibodies to the N-terminal SERT region did not recognize either of the two cleavage products, while antibodies to the central and C-terminal regions recognized both bands. The secondary band seen in the opioid group may represent a hypophosphorylated SERT fragment. These changes in SERT modifications and expression may result in altered fetal brain serotonergic neurotransmission, which could have neurodevelopmental implications. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication)
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17 pages, 2918 KiB  
Article
The Immobilization of an FGF2-Derived Peptide on Culture Plates Improves the Production and Therapeutic Potential of Extracellular Vesicles from Wharton’s Jelly Mesenchymal Stem Cells
by Youngseo Lee, Kyung-Min Lim, Hanbit Bong, Soo-Bin Lee, Tak-Il Jeon, Su-Yeon Lee, Hee-Sung Park, Ji-Young Kim, Kwonwoo Song, Geun-Ho Kang, Se-Jong Kim, Myeongjin Song and Ssang-Goo Cho
Int. J. Mol. Sci. 2024, 25(19), 10709; https://doi.org/10.3390/ijms251910709 - 4 Oct 2024
Viewed by 866
Abstract
The skin is an essential organ that protects the body from external aggressions; therefore, damage from various wounds can significantly impair its function, and effective methods for regenerating and restoring its barrier function are crucial. This study aimed to mass-produce wound-healing exosomes using [...] Read more.
The skin is an essential organ that protects the body from external aggressions; therefore, damage from various wounds can significantly impair its function, and effective methods for regenerating and restoring its barrier function are crucial. This study aimed to mass-produce wound-healing exosomes using a fragment of the fibroblast growth factor 2 (FGF2)-derived peptide (FP2) to enhance cell proliferation and exosome production. Our experiments demonstrated increased cell proliferation when Wharton’s jelly mesenchymal stem cells (WJ MSCs) were coated with FP2. Exosomes from FP2-coated WJ MSCs were analyzed using nanoparticle-tracking analysis, transmission electron microscopy, and Western blotting. Subsequently, fibroblasts were treated with these exosomes, and their viability and migration effects were compared. Anti-inflammatory effects were also evaluated by inducing pro-inflammatory factors in RAW264.7 cells. The treatment of fibroblasts with FP2-coated WJ MSC-derived exosomes (FP2-exo) increased the expression of FGF2, confirming their wound-healing effect in vivo. Overall, the results of this study highlight the significant impact of FP2 on the proliferation of WJ MSCs and the anti-inflammatory and wound-healing effects of exosomes, suggesting potential applications beyond wound healing. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication)
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16 pages, 11535 KiB  
Article
Modulation of the Oncogenic LINE-1 Regulatory Network in Non-Small Cell Lung Cancer by Exosomal miRNAs
by Abeer A. I. Hassanin and Kenneth S. Ramos
Int. J. Mol. Sci. 2024, 25(19), 10674; https://doi.org/10.3390/ijms251910674 - 3 Oct 2024
Viewed by 963
Abstract
Several microRNAs (miRNAs), including miR-221-5p, Let-7b-5p, miR-21-5p, miR-9-5p, miR-126-3p, and miR-222-3p, were recently found to be enriched in circulating exosomes of patients with non-small cell lung cancers (NSCLCs). These miRNAs distinguished cancer cases from controls with high precision and were predicted to modulate [...] Read more.
Several microRNAs (miRNAs), including miR-221-5p, Let-7b-5p, miR-21-5p, miR-9-5p, miR-126-3p, and miR-222-3p, were recently found to be enriched in circulating exosomes of patients with non-small cell lung cancers (NSCLCs). These miRNAs distinguished cancer cases from controls with high precision and were predicted to modulate the expression of genes within the oncogenic LINE-1 regulatory network. To test this hypothesis, plasma exosomes from controls, early, and late-stage NSCLC patients were co-cultured with non-tumorigenic lung epithelial cells for 72 h and processed for measurements of gene expression. Exosomes from late-stage NSCLC patients markedly increased the mRNA levels of LINE-1 ORF1 and ORF2, as well as the levels of target miRNAs in naïve recipient cells compared to saline or control exosomes. Late-stage exosomes also modulated the expression of oncogenic targets within the LINE-1 regulatory network, namely, ICAM1, AGL, RGS3, RGS13, VCAM1, and TGFβ1. In sharp contrast, exosomes from controls or early-stage NSCLC patients inhibited LINE-1 expression, along with many of the genetic targets within the LINE-1 regulatory network. Thus, late-stage NSCLC exosomes activate LINE-1 and miRNA-regulated oncogenic signaling in non-tumorigenic, recipient lung bronchial epithelial cells. These findings raise important questions regarding lung cancer progression and metastasis and open the door for the exploration of new therapeutic interventions. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication)
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13 pages, 3401 KiB  
Article
Oral Microbially-Induced Small Extracellular Vesicles Cross the Blood–Brain Barrier
by Mahmoud Elashiry, Angelica Carroll, Jessie Yuan, Yutao Liu, Mark Hamrick, Christopher W. Cutler, Qin Wang and Ranya Elsayed
Int. J. Mol. Sci. 2024, 25(8), 4509; https://doi.org/10.3390/ijms25084509 - 20 Apr 2024
Cited by 1 | Viewed by 2185
Abstract
Porphyromonas gingivalis (Pg) and its gingipain proteases contribute to Alzheimer’s disease (AD) pathogenesis through yet unclear mechanisms. Cellular secretion of small extracellular vesicles or exosomes (EXO) increases with aging as part of the senescence-associated secretory phenotype (SASP). We have shown that EXO isolated [...] Read more.
Porphyromonas gingivalis (Pg) and its gingipain proteases contribute to Alzheimer’s disease (AD) pathogenesis through yet unclear mechanisms. Cellular secretion of small extracellular vesicles or exosomes (EXO) increases with aging as part of the senescence-associated secretory phenotype (SASP). We have shown that EXO isolated from Pg-infected dendritic cells contain gingipains and other Pg antigens and transmit senescence to bystander gingival cells, inducing alveolar bone loss in mice in vivo. Here, EXO were isolated from the gingiva of mice and humans with/without periodontitis (PD) to determine their ability to penetrate the blood–brain barrier (BBB) in vitro and in vivo. PD was induced by Pg oral gavage for 6 weeks in C57B6 mice. EXO isolated from the gingiva or brain of donor Pg-infected (PD EXO) or control animals (Con EXO) were characterized by NTA, Western blot, and TEM. Gingival PD EXO or Con EXO were labeled and injected into the gingiva of uninfected WT mouse model. EXO biodistribution in brains was tracked by an in vivo imaging system (IVIS) and confocal microscopy. The effect of human PD EXO on BBB integrity and permeability was examined using TEER and FITC dextran assays in a human in vitro 3D model of the BBB. Pg antigens (RGP and Mfa-1) were detected in EXO derived from gingival and brain tissues of donor Pg-infected mice. Orally injected PD EXO from donor mice penetrated the brains of recipient uninfected mice and colocalized with hippocampal microglial cells. IL-1β and IL-6 were expressed in human PD EXO and not in Con EXO. Human PD EXO promoted BBB permeability and penetrated the BBB in vitro. This is the first demonstration that microbial-induced EXO in the oral cavity can disseminate, cross the BBB, and may contribute to AD pathogenesis. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication)
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18 pages, 10160 KiB  
Article
Comprehensive Analysis of Exosomal MicroRNAs Derived from UVB-Irradiated Keratinocytes as Potential Melanogenesis Regulators
by Jee-Hoe Yoon, Chan-Song Jo and Jae-Sung Hwang
Int. J. Mol. Sci. 2024, 25(6), 3095; https://doi.org/10.3390/ijms25063095 - 7 Mar 2024
Cited by 2 | Viewed by 1300
Abstract
The exosomes derived from keratinocytes can have a substantial impact on melanogenesis by influencing melanocytes. MicroRNAs (miRNAs) encapsulated within exosomes are implicated in the control of melanogenesis, particularly when under the influence of UVB irradiation. This investigation explores UVB-induced exosomal miRNAs from keratinocytes [...] Read more.
The exosomes derived from keratinocytes can have a substantial impact on melanogenesis by influencing melanocytes. MicroRNAs (miRNAs) encapsulated within exosomes are implicated in the control of melanogenesis, particularly when under the influence of UVB irradiation. This investigation explores UVB-induced exosomal miRNAs from keratinocytes as potential regulators of melanogenesis. UVB-irradiated, keratinocyte-derived exosomes were observed to augment melanogenesis in melanocytes, resulting in an upregulation of MITF, TRP1, TRP2, and TYR expression compared to non-UVB-irradiated exosomes. Additionally, a subset of exosomal miRNAs was differentially selected and confirmed to exert both enhancing and inhibitory effects on melanogenesis through functional assays. Notably, hsa-miR-644a, hsa-miR-365b-5p, and hsa-miR-29c-3p were found to upregulate melanogenesis, while hsa-miR-18a-5p, hsa-miR-197-5p, and hsa-miR-4281 downregulated melanogenesis. These findings suggest the involvement of keratinocyte-derived exosomal miRNAs in melanogenesis regulation within melanocytes. The expression levels of exosomal miRNAs from keratinocytes exhibited a UVB-dependent increase, indicating a potential role for these miRNAs as regulators of melanogenesis in response to UVB irradiation. Furthermore, melanogenesis was found to be dependent on exosomes derived from keratinocytes. This underscores the potential of UVB-induced exosomal miRNAs derived from keratinocytes as regulators of melanogenesis. Moreover, this study unveils a significant role for exosomes in melanocyte pigmentation, presenting a novel pathway in the intricate process of melanogenesis. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication)
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Review

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22 pages, 4192 KiB  
Review
Exosome-Laden Hydrogels as Promising Carriers for Oral and Bone Tissue Engineering: Insight into Cell-Free Drug Delivery
by Cassandra Villani, Prasathkumar Murugan and Anne George
Int. J. Mol. Sci. 2024, 25(20), 11092; https://doi.org/10.3390/ijms252011092 - 15 Oct 2024
Viewed by 1060
Abstract
Mineralization is a key biological process that is required for the development and repair of tissues such as teeth, bone and cartilage. Exosomes (Exo) are a subset of extracellular vesicles (~50–150 nm) that are secreted by cells and contain genetic material, proteins, lipids, [...] Read more.
Mineralization is a key biological process that is required for the development and repair of tissues such as teeth, bone and cartilage. Exosomes (Exo) are a subset of extracellular vesicles (~50–150 nm) that are secreted by cells and contain genetic material, proteins, lipids, nucleic acids, and other biological substances that have been extensively researched for bone and oral tissue regeneration. However, Exo-free biomaterials or exosome treatments exhibit poor bioavailability and lack controlled release mechanisms at the target site during tissue regeneration. By encapsulating the Exos into biomaterials like hydrogels, these disadvantages can be mitigated. Several tissue engineering approaches, such as those for wound healing processes in diabetes mellitus, treatment of osteoarthritis (OA) and cartilage degeneration, repair of intervertebral disc degeneration, and cardiovascular diseases, etc., have been exploited to deliver exosomes containing a variety of therapeutic and diagnostic cargos to target tissues. Despite the significant efficacy of Exo-laden hydrogels, their use in mineralized tissues, such as oral and bone tissue, is very sparse. This review aims to explore and summarize the literature related to the therapeutic potential of hydrogel-encapsulated exosomes for bone and oral tissue engineering and provides insight and practical procedures for the development of future clinical techniques. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication)
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29 pages, 1080 KiB  
Review
Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease
by Sohil Amin, Hamed Massoumi, Deepshikha Tewari, Arnab Roy, Madhurima Chaudhuri, Cedra Jazayerli, Abhi Krishan, Mannat Singh, Mohammad Soleimani, Emine E. Karaca, Arash Mirzaei, Victor H. Guaiquil, Mark I. Rosenblatt, Ali R. Djalilian and Elmira Jalilian
Int. J. Mol. Sci. 2024, 25(5), 2730; https://doi.org/10.3390/ijms25052730 - 27 Feb 2024
Cited by 3 | Viewed by 4097
Abstract
Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect [...] Read more.
Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem cell-derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue-specific EVs or cell type-specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in the signaling for physiological function and the maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines the current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states. Full article
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication)
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