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Exosomes—3rd Edition
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Exosomes—3rd 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: 20 October 2025 | Viewed by 5227

Special Issue Editor

Dr. Abdelnaby Khalyfa

E-Mail
Guest Editor
Robert C. Byrd Biotechnology Science Center, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA
Interests: genetic markers; sleep apnea; exosomes; single cell; snRNA-seq; metabolic dysfunction; animal models for sleep apnea
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Intercellular Communication between neighbored and distant cells are crucial for cell survival and responding to endocrine signaling. Exosomes, a class of extracellular vesicle (EVs) involved in cell to cell communication, are released by most of all biological fluids and emerging as novel cell-cell communication mediators in physiological and pathological conditions. These exosomes differ from other EVs based on their biogenesis, release pathways, size content, and function. Furthermore, these exosomes have shown to carry cell-specific cargos such as lipids, proteins, and miRNAs, mRNAs, and other genetic materials, and can be selectively taken up by neighboring or distant cells far from their release, which may ultimately reprogram the recipient cells distal from their release. Thus, exosomes and their biologically active cargos may offer potential biomarkers of diagnosis and therapeutic targets in a range of diseases, such as chronic inflammation, obesity, cardiovascular, neurodegenerative diseases, metabolic diseases, and tumors. This special issue aims to present new knowledge and covers all the topics relevant to exosomes in human cancers, cardiovascular, obesity, sleep, and neurogenerative deficit. We invite researchers to contribute either with original research or review articles focusing on every aspect regarding the role and function of exosomes in healthy and pathological conditions including the onset and progression of cancer, sleep, and heart diseases.

Due to the success of the 1st and 2nd editions, we would like to add more results and new insights from recent research projects.

https://www.mdpi.com/journal/ijms/special_issues/exosome

https://www.mdpi.com/journal/ijms/special_issues/VD106X1HQK

You can read more my publications at the following link: https://pubmed.ncbi.nlm.nih.gov/?term=khalyfa+a%2C+exosomes&sort=date&show_snippets=off

Dr. Abdelnaby Khalyfa
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.

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Keywords

  • extracellular vesicles (EVs)
  • exosomes
  • cancer
  • sleep cardiovascular diseases
  • lung disease and upper airways
  • obesity
  • sleep and end-organ morbidity

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Published Papers (4 papers)

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Research

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14 pages, 1651 KiB  
Article
Extracellular Vesicle Abundance, but Not a High Aggregation-Prone Peptide Cargo, Is Associated with Dihydroartemisinin Exposure in Plasmodium falciparum
by Kwesi Z. Tandoh, Yunuen Avalos-Padilla, Prince Ameyaw, Elisabeth K. Laryea-Akrong, Gordon A. Awandare, Michael David Wilson, Neils B. Quashie, Xavier Fernàndez-Busquets and Nancy O. Duah-Quashie
Int. J. Mol. Sci. 2025, 26(9), 3962; https://doi.org/10.3390/ijms26093962 - 22 Apr 2025
Abstract
Our understanding of the molecular mechanisms undergirding artemisinin (ART) resistance in Plasmodium falciparum is currently based on two organizing principles: reduced hemoglobin trafficking into the digestive food vacuole, resulting in lower levels of activated ART, and increased tolerance to ART-induced oxidative stress in [...] Read more.
Our understanding of the molecular mechanisms undergirding artemisinin (ART) resistance in Plasmodium falciparum is currently based on two organizing principles: reduced hemoglobin trafficking into the digestive food vacuole, resulting in lower levels of activated ART, and increased tolerance to ART-induced oxidative stress in the infected erythrocyte. We had previously proposed an extracellular vesicle (EV) export model of ART resistance in P. falciparum. This model predicts that EV abundance will be altered by ART exposure and that the peptide cargo of EVs from the ART-exposed condition will be enriched with aggregation-prone peptides. We tested the predictions of the EV export hypothesis in this study using in vitro culture assays of an ART-resistant transgenic line engineered on a 3D7 background (R561H) and a 3D7 knock-out line (PfVps60KO) with deficient EV production phenotype. EV enrichment was obtained from in vitro parasite culture supernatants via a series of ultracentrifugation and filtration steps, followed by size exclusion chromatography. A quality check on EVs was performed using dynamic light scattering. Liquid chromatography with tandem mass spectrometry was used to determine the proteome cargo from extracted EVs, and parasite peptides were queried for aggregation-prone tendency using open-access software. We report that dihydroartemisinin (DHA) exposure was positively correlated with EV abundance (coefficient estimate = 1038.58, confidence interval of 194.86–1882.30, and p-value = 0.018) and suggests that EV biogenesis is part of the parasite’s response to DHA/ART. Furthermore, our findings suggest the expression of a non-constitutive DHA-induced alternate EV biogenesis pathway as the PfVps60KO was observed to produce the highest number of EVs under DHA exposure. Finally, we show that EVs from both ART-susceptible and resistant parasites under DHA exposure carry a cargo of Chorein N-terminal domain-containing protein (PF3D7_1021700) with a high aggregation-prone index (prion-like domain [PrLD] score = 26.5) out of nine identified parasite peptides. The former of these findings is in concordance with the EV export hypothesis, which posits that the removal of DHA/ART-induced aggregated and/or misfolded peptides is critical to the parasite’s survival under DHA/ART exposure. This observation further implicates EVs in the development of the ART-resistant phenotype. However, the finding of one aggregation-prone peptide out of the nine parasite proteins in the EV cargo does not sufficiently support the EV export hypothesis. Future replicates of this study and further interrogations of the EV export hypothesis are needed. Full article
(This article belongs to the Special Issue Exosomes—3rd Edition)
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15 pages, 2167 KiB  
Article
Small Extracellular Vesicles Derived from Cord Blood Plasma and Placental Mesenchymal Stem Cells Attenuate Acute Lung Injury Induced by Lipopolysaccharide (LPS)
by Ranga P. Thiruvenkataramani, Amal Abdul-Hafez, Tulasi Kesaraju, Hend Mohamed, Sherif Abdelfattah Ibrahim, Amira Othman, Hattan Arif, Ahmed A. Zarea, Mohammed Abdulmageed, Myrna Gonzalez Arellano, Tarek Mohamed, Masamitsu Kanada, Burra V. Madhukar and Said A. Omar
Int. J. Mol. Sci. 2025, 26(1), 75; https://doi.org/10.3390/ijms26010075 - 25 Dec 2024
Cited by 1 | Viewed by 1938
Abstract
Sepsis is a risk factor associated with increasing neonatal morbidity and mortality, acute lung injury, and chronic lung disease. While stem cell therapy has shown promise in alleviating acute lung injury, its effects are primarily exerted through paracrine mechanisms rather than local engraftment. [...] Read more.
Sepsis is a risk factor associated with increasing neonatal morbidity and mortality, acute lung injury, and chronic lung disease. While stem cell therapy has shown promise in alleviating acute lung injury, its effects are primarily exerted through paracrine mechanisms rather than local engraftment. Accumulating evidence suggests that these paracrine effects are mediated by mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs), which play a critical role in immune system modulation and tissue regeneration. sEVs contain a diverse cargo of mRNA, miRNA, and proteins, contributing to their therapeutic potential. We hypothesize that sEVs derived from three distinct sources, cord blood plasma (CBP), Wharton jelly (WJ), and placental (PL) MSCs, may prevent the cytotoxicity induced by E. coli lipopolysaccharide (LPS) in lung alveolar epithelial cells. Objective: To determine the effects of CBP-, WJ-, and PL-MSCs-derived sEVs on cell viability, apoptosis, and proinflammatory cytokine production in alveolar epithelial cells and monocytes following LPS treatment. sEVs were collected from conditioned media of PL-MSCs, WJ-MSCs, and CBP using 50 nm membrane filters. sEVs were characterized based on nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting techniques. The protein concentration of isolated sEVs was used to standardize treatment doses. A549 cells and monocyte THP-1 cells were cultured and exposed to LPS in the presence or absence of sEVs for 72 h. Cell viability was measured using CellTiter-Glo 2.0 chemiluminescence-based assay. For cytokine analysis, A549 and THP-1 cells were pre-incubated for 24 h with or without PL- and CBP-sEVs, followed by exposure to LPS or control conditions for an additional 24 h. The conditioned media were collected, and interleukin-6 (IL-6) and interleukin-8 (IL-8) levels were quantified using ELISA. LPS treatment significantly reduced the viability of both A549 and THP-1 cells. The presence of CB- or WJ-sEVs significantly increased cell viability compared to controls. Cells treated with PL-sEVs showed increased cell viability but did not reach statistical significance. LPS-treated cells showed a significant increase in apoptosis and elevated levels of pro-inflammatory cytokines IL-6 and IL-8. All three sEVs types (CBP-, WJ-, and PL-sEVs) significantly reduced LPS-induced apoptosis and IL-6 release. Interestingly, while WJ-sEVs decreased IL-8, both CBP- and PL-sEVs led to an increase in IL-8 compared to their respective controls. CBP-, PL-, and WJ-derived sEVs demonstrated protective effects against LPS-induced injury in alveolar epithelial cells and monocytes, as evidenced by increased cell viability and modulation of pro-inflammatory cytokine release. These findings suggest that placenta-derived sEVs have the potential to modulate the immune response, mitigate inflammation, and prevent end-organ damage in neonatal sepsis. Full article
(This article belongs to the Special Issue Exosomes—3rd Edition)
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8 pages, 8360 KiB  
Communication
Exosome Therapy: A Novel Approach for Enhancing Estrogen Levels in Perimenopause
by Samar Alkhrait, Mervat M. Omran, Mohammad Mousaei Ghasroldasht, Hang-Soo Park, Riham Katkhuda and Ayman Al-Hendy
Int. J. Mol. Sci. 2024, 25(13), 7075; https://doi.org/10.3390/ijms25137075 - 27 Jun 2024
Viewed by 1899
Abstract
Perimenopause significantly impacts women’s health globally, often managed with hormone replacement therapy (HRT) despite the associated risks. This study explores a novel alternative exosome therapy, aimed at stimulating estrogen production in ovarian tissues, thus offering a potential non-hormonal treatment for perimenopausal symptoms. Employing [...] Read more.
Perimenopause significantly impacts women’s health globally, often managed with hormone replacement therapy (HRT) despite the associated risks. This study explores a novel alternative exosome therapy, aimed at stimulating estrogen production in ovarian tissues, thus offering a potential non-hormonal treatment for perimenopausal symptoms. Employing ex vivo methodologies, ovarian cortex specimens from perimenopausal women were treated with exosomes derived from human umbilical cord mesenchymal stem cells and cultured under specific conditions (patent number: PCT/US2022/073467). The exosomes were produced under cyclic guanosine monophosphate (cGMP) conditions, ensuring high safety standards. Estrogen levels were quantified using enzyme-linked immunosorbent assay (ELISA), and gene expression changes in estrogen and follicle-stimulating hormone (FSH) receptors were assessed via quantitative polymerase chain reaction (PCR). Immunohistochemistry (IHC) was utilized to evaluate cellular proliferation and apoptotic markers. The results indicated a significant increase in estrogen levels and estrogen receptor-alpha (Erα) expression in treated tissues compared to controls. Additionally, a decrease in apoptotic markers and an increase in cellular proliferation markers were observed. These findings suggest that exosome therapy can effectively enhance estrogen production and modulate receptor sensitivity in perimenopausal ovarian tissues. This approach could serve as a safer alternative to HRT, aligning with the body’s natural regulatory mechanisms and potentially offering a more effective treatment option for managing perimenopausal symptoms. Full article
(This article belongs to the Special Issue Exosomes—3rd Edition)
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Review

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11 pages, 1331 KiB  
Review
Exosomes in Breast Milk: Their Impact on the Intestinal Microbiota of the Newborn and Therapeutic Perspectives for High-Risk Neonates
by Delia Cristóbal-Cañadas, Rocio Parrón-Carrillo and Tesifón Parrón-Carreño
Int. J. Mol. Sci. 2025, 26(7), 3421; https://doi.org/10.3390/ijms26073421 - 5 Apr 2025
Viewed by 277
Abstract
Breast milk exosomes are essential for the nutrition and immune development of the newborn. These 30–150 nm extracellular vesicles contain microRNAs (miRNAs), mesessenger RNAS (mRNA)s, proteins and lipids that facilitate cellular communication and modulate the neonatal immune system. In this article, we analyse [...] Read more.
Breast milk exosomes are essential for the nutrition and immune development of the newborn. These 30–150 nm extracellular vesicles contain microRNAs (miRNAs), mesessenger RNAS (mRNA)s, proteins and lipids that facilitate cellular communication and modulate the neonatal immune system. In this article, we analyse the impact of breast milk exosomes on the intestinal microbiota of the newborn, especially in high-risk neonates such as preterm infants or neonates at risk of necrotising enterocolitis (NEC). Exosomes promote the colonisation of beneficial bacteria such as Bifidobacterium and Lactobacillus and strengthen the intestinal barrier. They also regulate the immune response, balancing defence against pathogens and tolerance to non-pathogenic antigens. This effect is key for high-risk infants, who benefit from their anti-inflammatory and preventive properties against complications such as NEC. Research points to their potential therapeutic uses in neonatal care, opening up new opportunities to improve the health of vulnerable newborns through the protective effects of breast milk exosomes. Full article
(This article belongs to the Special Issue Exosomes—3rd Edition)
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