Extracellular Vesicles for Diagnosis and Treatment of Human Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 4019

Special Issue Editor


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Guest Editor
Department of Chemistry and Biomolecular Sciences, John L. Holmes Mass Spectrometry Facility, Faculty of Science, University of Ottawa, Ottawa, ON K1N6N5, Canada
Interests: extracellular vesicles; breast cancer; mass spectrometry; proteomics; phosphoproteomics; metabolomics; bioinformatics; biomarker
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Special Issue Information

Dear Colleagues,

Within the last decade, extracellular vesicles (EVs) have been recognized as a novel mechanism of intra- and intercellular communication via the delivery of bioactive molecules that mainly comprise proteins, metabolites, lipids, and nucleic acids, including messenger RNAs (mRNAs) and microRNAs (miRNAs). EVs are also found in biological fluids such as blood, saliva, cerebrospinal fluid and urine. Furthermore, they are implicated in various pathogeneses and could contain biomarkers associated with specific human diseases. Moreover, profiling the contents of EVs may further elucidate their role in disease progression and treatment, as well as enable the identification of therapeutic targets. In recent years, it has been proposed that EVs could be utilized in the development of novel therapies. However, in order to employ EVs for the diagnosis and treatment of human diseases, appropriate methods for their isolation must be developed, and their molecular composition, functionality, and the distribution of EV cargo must be investigated. The aim of this Special Issue is to publish research related to all aspects of EVs for the diagnosis and treatment of human diseases.

Dr. Zoran Minic
Guest Editor

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Keywords

  • human diseases
  • extracellular vesicles
  • biomarkers
  • diagnosis
  • prognosis
  • therapeutic targets
  • therapeutic applications
  • EV engineering
  • physiology
  • pathology

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Published Papers (3 papers)

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Research

15 pages, 22554 KiB  
Article
Neutrophil- and Endothelial Cell-Derived Extracellular Microvesicles Are Promising Putative Biomarkers for Breast Cancer Diagnosis
by Thayse Batista Moreira, Marina Malheiros Araújo Silvestrini, Ana Luiza de Freitas Magalhães Gomes, Kerstin Kapp Rangel, Álvaro Percínio Costa, Matheus Souza Gomes, Laurence Rodrigues do Amaral, Olindo Assis Martins-Filho, Paulo Guilherme de Oliveira Salles, Letícia Conceição Braga and Andréa Teixeira-Carvalho
Biomedicines 2025, 13(3), 587; https://doi.org/10.3390/biomedicines13030587 - 27 Feb 2025
Viewed by 575
Abstract
Introduction: Breast cancer (BC) is a disease that affects about 2.2 million people worldwide. The prognosis and treatment of these patients depend on clinical and histopathologic staging, in which more aggressive cancers need a less conservative therapeutic approach. Previous studies showed that patients [...] Read more.
Introduction: Breast cancer (BC) is a disease that affects about 2.2 million people worldwide. The prognosis and treatment of these patients depend on clinical and histopathologic staging, in which more aggressive cancers need a less conservative therapeutic approach. Previous studies showed that patients with BC have an increased frequency of systemic microvesicles (MVs) that are associated with invasion, progression, and metastasis, which can be used in liquid biopsy to predict the therapeutic response in individualized treatment. Objective: This study proposes the development of a minimally invasive BC diagnostic panel and follow-up biomarkers as a complementary method to screen patients. Methods: The quantification of circulating MVs in 48 healthy women and 100 BC patients who attended the Mário Penna Institute between 2019 and 2022 was performed by flow cytometry. In addition, the MVs of BC patients were analyzed before treatment and 6, 12, and 24 months post-treatment. Machine learning approaches were employed to determine the performance of MVs to identify BC and to propose BC classifier algorithms. Results: Patients with BC had more neutrophil- and endothelial cell-derived MVs than controls before treatment. After treatment, all MV populations were decreased compared to pre-treatment, but leukocyte- and erythrocyte-derived MVs were increased at 12 months after treatment, before decreasing again at 24 months. Conclusions: Performance analyses and machine learning approaches pointed out that MVs from neutrophils and endothelial cells are the best candidates for BC diagnostic biomarkers. Neutrophil- and endothelial cell-derived MVs are putative candidates for BC biomarkers to be employed as screening tests for BC diagnosis. Full article
(This article belongs to the Special Issue Extracellular Vesicles for Diagnosis and Treatment of Human Diseases)
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10 pages, 948 KiB  
Communication
Modeling the Impact of Extracellular Vesicle Cargoes in the Diagnosis of Coronary Artery Disease
by Peter McGranaghan, Éva Pallinger, Nóra Fekete, Pál Maurovich-Horvát, Zsófia Drobni, Béla Merkely, Luigi Menna, Edit I. Buzás and Hargita Hegyesi
Biomedicines 2024, 12(12), 2682; https://doi.org/10.3390/biomedicines12122682 - 25 Nov 2024
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Abstract
Objectives: We aimed to assess the relationship among circulating extracellular vesicles (EVs), hypoxia-related proteins, and the conventional risk factors of life-threatening coronary artery disease (CAD) to find more precise novel biomarkers. Methods: Patients were categorized based on coronary CT angiography. Patients [...] Read more.
Objectives: We aimed to assess the relationship among circulating extracellular vesicles (EVs), hypoxia-related proteins, and the conventional risk factors of life-threatening coronary artery disease (CAD) to find more precise novel biomarkers. Methods: Patients were categorized based on coronary CT angiography. Patients with a Segment Involvement Score > 5 were identified as CAD patients. Individuals with a Segment Involvement Score < 5 were considered control subjects. The characterization of EVs and analysis of the plasma concentration of growth differentiation factor-15 were performed using multicolor or bead-based flow cytometry. The plasma protein levels of glycogen phosphorylase, muscle form, clusterin, and carboxypeptidase N subunit 1 were determined using an enzyme-linked immunosorbent assay. Multiple logistic regression was used to determine the association of the biomarkers with the CAD outcome after accounting for established risk factors. The analysis was built in three steps: first, we included the basic clinical and laboratory variables (Model 1), then we integrated the plasma protein values (Model 2), and finally, we complemented it with the circulating EV pattern (Model 3). To assess the discrimination value of the models, an area under (AUC) the receiver operating curve was calculated and compared across the three models. Results: The area under the curve (AUC) values were 0.68, 0.77, and 0.84 in Models 1, 2, and 3, respectively. The variables with the greatest impact on the AUC values were hemoglobin (0.2 (0.16–0.26)) in Model 1, carboxypeptidase N subunit 1 (0.12 (0.09–0.14)) in Model 2, and circulating CD41+/CD61+ EVs (0.31 (0.15–0.5)) in Model 3. A correlation analysis showed a significant impact of circulating CD41+/CD61+ platelet-derived EVs (p = 0.03, r = −0.4176) in Model 3. Conclusions: Based on our results, the circulating EV profile can be used as a supportive biomarker, along with the conventional laboratory markers of CAD, and it enables a more sensitive, non-invasive diagnostic analysis of CAD. Full article
(This article belongs to the Special Issue Extracellular Vesicles for Diagnosis and Treatment of Human Diseases)
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12 pages, 2623 KiB  
Article
Tetraspanins, GLAST and L1CAM Quantification in Single Extracellular Vesicles from Cerebrospinal Fluid and Serum of People with Multiple Sclerosis
by Rocío Del Carmen Bravo-Miana, Jone Karmele Arizaga-Echebarria, Valeria Sabas-Ortega, Hirune Crespillo-Velasco, Alvaro Prada, Tamara Castillo-Triviño and David Otaegui
Biomedicines 2024, 12(10), 2245; https://doi.org/10.3390/biomedicines12102245 - 2 Oct 2024
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Abstract
Objective: This study aimed to unravel the single tetraspanin pattern of extracellular vesicles (EVs), L1CAM+ and GLAST+ EV levels as diagnostic biomarkers to stratify people with multiple sclerosis (pwMS), specifically relapsing–remitting (RRMS) and primary progressive (PPMS). Methods: The ExoView platform was [...] Read more.
Objective: This study aimed to unravel the single tetraspanin pattern of extracellular vesicles (EVs), L1CAM+ and GLAST+ EV levels as diagnostic biomarkers to stratify people with multiple sclerosis (pwMS), specifically relapsing–remitting (RRMS) and primary progressive (PPMS). Methods: The ExoView platform was used to directly track single EVs using a clinically feasible volume of cerebrospinal fluid (CSF) and serum samples. This technology allowed us to examine the patterns of classical tetraspanin and quantify the levels of L1CAM and GLAST proteins, commonly used to immunoisolate putative neuron- and astrocyte-derived EVs. Results: The tetraspanin EV pattern does not allow us to differentiate RRMS, PPMS and non-MS donors neither in CSF nor serum, but this was associated with the type of biofluid. L1CAM+ and GLAST+ EVs showed a very low presence of tetraspanin proteins. Additionally, a significant decrease in the particle count of L1CAM+ EVs was detected in L1CAM-captured spots, and L1CAM+ and GLAST+ EVs decreased in GLAST-captured spots in the CSF from PPMS subjects compared to RRMS. Interestingly, only GLAST+ EVs exhibited a lower quantity in the CSF from PPMS compared to both MS and non-MS samples. Finally, GLAST+ EVs demonstrated a medium negative and significative correlation with GFAP levels—a biomarker of MS progression, astrocyte damage and neurodegenerative processes. Conclusions: ExoView technology could track neural EV biomarkers and be potentially useful in the diagnostic evaluation and follow-up of pwMS. GLAST+ EVs might provide insights into the etiology of PPMS and could offer small windows to elucidate the molecular mechanisms behind its clinical presentation. Full article
(This article belongs to the Special Issue Extracellular Vesicles for Diagnosis and Treatment of Human Diseases)
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