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Biological Functions and Therapeutic Applications of Extracellular Vesicles

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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 July 2024 | Viewed by 3346

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Dr. Regina Golan-Gerstl

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Guest Editor

Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem 9112001, Israel
Interests: milk and breastfeeding; miRNA; extracellular vesicles; exosomes; colitis
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Dear Colleagues,

Extracellular vesicles (EVs) are lipid bilayer particles secreted by cells into the extracellular space. They contain various bioactive molecules, including proteins, nucleic acids (such as microRNAs), and lipids. These cargo molecules are protected within the EVs, enabling their stable transfer between cells and influencing cellular functions and signaling pathways.

EVs have significant therapeutic potential and can serve as vehicles for drug delivery, gene therapy, and other therapeutic interventions, offering innovative strategies for various diseases such as cancer, neurodegenerative disorders, immune-related conditions, and cardiovascular diseases. Additionally, EVs can be loaded with therapeutic cargo, and the cells responsible for EV secretion can be genetically modified to alter the cargo content and therapeutic properties of the EVs. Given their roles in intercellular communication and potential therapeutic applications, EVs have attracted considerable scientific attention.

This Special Issue welcomes articles focusing on the biology and therapeutic applications of extracellular EVs, with particular interest in EVs derived from natural sources such as milk or other food products. We seek innovative studies shedding light on the intercellular communication, cargo content, and therapeutic potential of EVs.

As the Guest Editor of this Special Issue, I hope that this collection of articles will serve as a valuable reference for teaching and research, stimulating discussions and inspiring new avenues of research in the field of EVs.

Dr. Regina Golan-Gerstl
Guest Editor

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Keywords

miRNA
extracellular vesicles
exosomes
colitis

Published Papers (3 papers)

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Research

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20 pages, 5113 KiB

Open AccessArticle

The Difference of Milk-Derived Extracellular Vesicles from Cow Colostrum and Mature Milk on miRNAs Expression and Protecting Intestinal Epithelial Cells against Lipopolysaccharide Damage

by Wenju Liu, Chao Du, Liangkang Nan, Chunfang Li, Haitong Wang, Yikai Fan and Shujun Zhang

Int. J. Mol. Sci. 2024, 25(7), 3880; https://doi.org/10.3390/ijms25073880 - 30 Mar 2024

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Abstract

Intestinal epithelial cells (IECs) play crucial roles in forming an essential barrier, providing host defense against pathogens and regulating nutrients absorption. Milk-derived extracellular vesicles (EVs) within its miRNAs are capable of modulating the recipient cell function. However, the differences between colostrum and mature milk EVs and their biological function in attenuating intestinal epithelial cell injury remain poorly understood. Thus, we carried out the present study to characterize the difference between colostrum and mature milk-derived miRNA of EVs and the effect of colostrum and mature milk EVs on the proliferation, apoptosis, proinflammatory cytokines and intestinal epithelial barrier related genes in IEC-6 induced by LPS. Differential expression of 329 miRNAs was identified between colostrum and mature milk EVs, with 185 miRNAs being downregulated and 144 upregulated. In addition, colostrum contains a greater number and protein concentration of EVs than mature milk. Furthermore, compared to control, EVs derived from colostrum significantly inhibited the expression of apoptosis- (Bax, p53, and caspase-3) and proinflammatory-related genes (TNFα, IL6, and IL1β). EVs derived from mature milk did not affect expression of apoptosis-related genes (Bax, p53, bcl2, and caspase-3). The EVs derived from mature milk significantly inhibited the expression of proinflammatory-related genes (TNFα and IL6). Western blot analysis also indicated that colostrum and mature milk EVs significantly decreased the apoptosis of IEC-6 cells. The EdU assay results showed that colostrum and mature milk EVs significantly increased the proliferation of IEC-6 cells. The expression of intestinal barrier-related genes (TJP1, CLDN1, OCLN, CDX2, MUC2, and IGF1R) was significantly promoted in IEC-6 cells after colostrum and mature milk EVs addition. Importantly, colostrum and mature milk EVs significantly relieved the LPS-induced inhibition of proliferation and intestinal barrier-related genes expression and attenuated apoptosis and proinflammatory responses induced by LPS in IEC-6 cells. Flow cytometry and Western blot analysis also indicated that colostrum and mature milk EVs significantly affect the apoptosis of IEC-6 cells induced by LPS. The results also indicated that EVs derived from colostrum had better effects on inhibiting the apoptosis- and proinflammatory cytokines-related genes expression. However, the EVs derived from mature milk exhibited beneficial effects on intestinal epithelial barrier protection. The present study will provide a better understanding of the role of EVs derived from colostrum and milk in dairy cows with different responses in the regulation of intestinal cells function, and also presents new evidence for the change of EVs cargos during various stages of lactation. Full article

(This article belongs to the Special Issue Biological Functions and Therapeutic Applications of Extracellular Vesicles)

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24 pages, 5441 KiB

Open AccessArticle

Multi-Omic Temporal Landscape of Plasma and Synovial Fluid-Derived Extracellular Vesicles Using an Experimental Model of Equine Osteoarthritis

by James R. Anderson, Emily Johnson, Rosalind Jenkins, Stine Jacobsen, Daniel Green, Marie Walters, Louise Bundgaard, Bas A. C. Hausmans, Guus van den Akker, Tim J. M. Welting, Alzbeta Chabronova, Yalda A. Kharaz, Emily J. Clarke, Victoria James and Mandy J. Peffers

Int. J. Mol. Sci. 2023, 24(19), 14888; https://doi.org/10.3390/ijms241914888 - 04 Oct 2023

Viewed by 1450

Abstract

Extracellular vesicles (EVs) contribute to osteoarthritis pathogenesis through their release into joint tissues and synovial fluid. Synovial fluid-derived EVs have the potential to be direct biomarkers in the causal pathway of disease but also enable understanding of their role in disease progression. Utilizing a temporal model of osteoarthritis, we defined the changes in matched synovial fluid and plasma-derived EV small non-coding RNA and protein cargo using sequencing and mass spectrometry. Data exploration included time series clustering, factor analysis and gene enrichment interrogation. Chondrocyte signalling was analysed using luciferase-based transcription factor activity assays. EV protein cargo appears to be more important during osteoarthritis progression than small non-coding RNAs. Cluster analysis revealed plasma-EVs represented a time-dependent response to osteoarthritis induction associated with supramolecular complexes. Clusters for synovial fluid-derived EVs were associated with initial osteoarthritis response and represented immune/inflammatory pathways. Factor analysis for plasma-derived EVs correlated with day post-induction and were primarily composed of proteins modulating lipid metabolism. Synovial fluid-derived EVs factors represented intermediate filament and supramolecular complexes reflecting tissue repair. There was a significant interaction between time and osteoarthritis for CRE, NFkB, SRE, SRF with a trend for osteoarthritis synovial fluid-derived EVs at later time points to have a more pronounced effect. Full article

(This article belongs to the Special Issue Biological Functions and Therapeutic Applications of Extracellular Vesicles)

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Review

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17 pages, 1903 KiB

Open AccessReview

Extracellular Vesicles: A Crucial Player in the Intestinal Microenvironment and Beyond

by Shumeng Wang, Junyi Luo, Hailong Wang, Ting Chen, Jiajie Sun, Qianyun Xi and Yongliang Zhang

Int. J. Mol. Sci. 2024, 25(6), 3478; https://doi.org/10.3390/ijms25063478 - 20 Mar 2024

Viewed by 617

Abstract

The intestinal ecological environment plays a crucial role in nutrient absorption and overall well-being. In recent years, research has focused on the effects of extracellular vesicles (EVs) in both physiological and pathological conditions of the intestine. The intestine does not only consume EVs from exogenous foods, but also those from other endogenous tissues and cells, and even from the gut microbiota. The alteration of conditions in the intestine and the intestinal microbiota subsequently gives rise to changes in other organs and systems, including the central nervous system (CNS), namely the microbiome–gut–brain axis, which also exhibits a significant involvement of EVs. This review first gives an overview of the generation and isolation techniques of EVs, and then mainly focuses on elucidating the functions of EVs derived from various origins on the intestine and the intestinal microenvironment, as well as the impacts of an altered intestinal microenvironment on other physiological systems. Lastly, we discuss the role of microbial and cellular EVs in the microbiome–gut–brain axis. This review enhances the understanding of the specific roles of EVs in the gut microenvironment and the central nervous system, thereby promoting more effective treatment strategies for certain associated diseases. Full article

(This article belongs to the Special Issue Biological Functions and Therapeutic Applications of Extracellular Vesicles)

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