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Grant support

This work was had grant support by a grant from Miguel Servet (CP15/00069; CPII20/00002 to Maria Gutierrez-Fernandez), Miguel Servet (CP20/00024 to Laura Otero-Ortega), a predoctoral fellowship (FI17/00188 to Mari Carmen Gomez-de Frutos; FI18/00026 to Fernando Laso-Garcia) from the Carlos III Health Institute Health Care Research Fund and was co-funded by the European Regional Development Fund (ERDF) and Talent Advanced Researchers' Grant from Comunidad Autonoma de Madrid (2019-T1/IND-13794 to Fernando de la Cuesta).

Analysis of institutional authors

De La Cuesta, FAuthorDiez-Tejedor, ECorresponding Author

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October 22, 2021
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Review
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Potential Roles of Extracellular Vesicles as Biomarkers and a Novel Treatment Approach in Multiple Sclerosis

Publicated to:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 22 (16): 9011- - 2021-08-01 22(16), DOI: 10.3390/ijms22169011

Authors: Gutierrez-Fernandez, Maria; de la Cuesta, Fernando; Tallon, Antonio; Cuesta, Inmaculada; Fernandez-Fournier, Mireya; Laso-Garcia, Fernando; Carmen Gomez-de Frutos, Mari; Diez-Tejedor, Exuperio; Otero-Ortega, Laura;

Affiliations

Univ Autonoma Madrid, La Paz Univ Hosp, Neurosci Area, Dept Neurol,IdiPAZ Hlth Res Inst,Neurol Sci & Cer, Madrid 28046, Spain - Author
Univ Autonoma Madrid, Sch Med, Dept Pharmacol & Therapeut, Madrid 28046, Spain - Author

Abstract

Extracellular vesicles (EVs) are a heterogeneous group of bilayer membrane-wrapped molecules that play an important role in cell-to-cell communication, participating in many physiological processes and in the pathogenesis of several diseases, including multiple sclerosis (MS). In recent years, many studies have focused on EVs, with promising results indicating their potential role as biomarkers in MS and helping us better understand the pathogenesis of the disease. Recent evidence suggests that there are novel subpopulations of EVs according to cell origin, with those derived from cells belonging to the nervous and immune systems providing information regarding inflammation, demyelination, axonal damage, astrocyte and microglia reaction, blood-brain barrier permeability, leukocyte transendothelial migration, and ultimately synaptic loss and neuronal death in MS. These biomarkers can also provide insight into disease activity and progression and can differentiate patients' disease phenotype. This information can enable new pathways for therapeutic target discovery, and consequently the development of novel treatments. Recent evidence also suggests that current disease modifying treatments (DMTs) for MS modify the levels and content of circulating EVs. EVs might also serve as biomarkers to help monitor the response to DMTs, which could improve medical decisions concerning DMT initiation, choice, escalation, and withdrawal. Furthermore, EVs could act not only as biomarkers but also as treatment for brain repair and immunomodulation in MS. EVs are considered excellent delivery vehicles. Studies in progress show that EVs containing myelin antigens could play a pivotal role in inducing antigen-specific tolerance of autoreactive T cells as a novel strategy for the treatment as "EV-based vaccines" for MS. This review explores the breakthrough role of nervous and immune system cell-derived EVs as markers of pathological disease mechanisms and potential biomarkers of treatment response in MS. In addition, this review explores the novel role of EVs as vehicles for antigen delivery as a therapeutic vaccine to restore immune tolerance in MS autoimmunity.

Keywords

antigen delivery systembiomarkersextracellular vesiclesmultiple sclerosisresponse to treatmentAntigen delivery systemBiomarkersComplexesEndothelial microparticlesExosomesExtracellular vesiclesMicrovesiclesMsMultiple sclerosisPlasmaProteomeReleaseResponse to treatmentVaccine-like treatmentVaccine‐like treatment

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 69/297, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations from Scopus Elsevier, it yields a value for the Field-Weighted Citation Impact from the Scopus agency: 1.82, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Field Citation Ratio (FCR) from Dimensions: 4.07 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-16, the following number of citations:

  • WoS: 10
  • Scopus: 22

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-16:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 60.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 64 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 8.85.
  • The number of mentions on the social network X (formerly Twitter): 4 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Gutierrez-Fernandez, M) and Last Author (Otero-Ortega, L).

the authors responsible for correspondence tasks have been DIEZ TEJEDOR, EXUPERIO and Otero-Ortega, L.