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Biological Functions and Therapeutic Applications of Extracellular Vesicles

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 7191

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Special Issue Editor

Dr. Regina Golan-Gerstl

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Guest Editor

Department of Pediatrics, Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
Interests: miRNA; extracellular vesicles; exosomes; colitis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

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

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Published Papers (5 papers)

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Research

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18 pages, 3892 KiB

Open AccessArticle

Exploring the Therapeutic Potential of Extracellular Vesicles Derived from Human Immature Dental Pulp Cells on Papillary Thyroid Cancer

by Michelli Ramires Teixeira, Anderson Lucas Alievi, Vitor Rodrigues da Costa, Irina Kerkis and Rodrigo Pinheiro Araldi

Int. J. Mol. Sci. 2024, 25(15), 8178; https://doi.org/10.3390/ijms25158178 - 26 Jul 2024

Viewed by 619

Abstract

Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) have been increasingly investigated for cancer therapy and drug delivery, and they offer an advanced cell-free therapeutic option. However, their overall effects and efficacy depend on various factors, including the MSC source and cargo content. In this study, we isolated EVs from the conditioned medium of human immature dental pulp stem cells (hIDPSC-EVs) and investigated their effects on two papillary thyroid cancer (PTC) cell lines (BCPAP and TPC1). We observed efficient uptake of hIDPSC-EVs by both PTC cell lines, with a notable impact on gene regulation, particularly in the Wnt signaling pathway in BCPAP cells. However, no significant effects on cell proliferation were observed. Conversely, hIDPSC-EVs significantly reduced the invasive capacity of both PTC cell lines after 120 h of treatment. These in vitro findings suggest the therapeutic potential of hIDPSC-EVs in cancer management and emphasize the need for further research to develop novel and effective treatment strategies. Furthermore, the successful internalization of hIDPSC-EVs by PTC cell lines underscores their potential use as nanocarriers for anti-cancer agents. Full article

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

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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

Cited by 1 | Viewed by 1334

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 - 4 Oct 2023

Cited by 3 | Viewed by 2074

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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15 pages, 1134 KiB

Open AccessReview

New Origins of Yeast, Plant and Bacterial-Derived Extracellular Vesicles to Expand and Advance Compound Delivery

by María Fernández-Rhodes, Cristina Lorca, Julia Lisa, Iolanda Batalla, Alfredo Ramos-Miguel, Xavier Gallart-Palau and Aida Serra

Int. J. Mol. Sci. 2024, 25(13), 7151; https://doi.org/10.3390/ijms25137151 - 28 Jun 2024

Cited by 1 | Viewed by 874

Abstract

Extracellular vesicles (EVs) constitute a sophisticated molecular exchange mechanism highly regarded for their potential as a next-generation platform for compound delivery. However, identifying sustainable and biologically safe sources of EVs remains a challenge. This work explores the emergence of novel sources of plant and bacterial-based EVs, such as those obtained from food industry by-products, known as BP-EVs, and their potential to be used as safer and biocompatible nanocarriers, addressing some of the current challenges of the field. These novel sources exhibit remarkable oral bioavailability and biodistribution, with minimal cytotoxicity and a selective targeting capacity toward the central nervous system, liver, and skeletal tissues. Additionally, we review the ease of editing these recently uncovered nanocarrier-oriented vesicles using common EV editing methods, examining the cargo-loading processes applicable to these sources, which involve both passive and active functionalization methods. While the primary focus of these novel sources of endogenous EVs is on molecule delivery to the central nervous system and skeletal tissue based on their systemic target preference, their use, as reviewed here, extends beyond these key applications within the biotechnological and biomedical fields. Full article

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

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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

Cited by 1 | Viewed by 1365

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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