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Multiple Sclerosis: Research in Remyelination, the Next Step

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A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (19 August 2022) | Viewed by 12745

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Special Issue Editors

Prof. Dr. Jorge Matias-Guiu

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Guest Editor

Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, 28040 Madrid, Spain
Interests: multiple sclerosis; remyelination; cell therapy; neurodegeneration; neurogeneti

Dr. Ulises Gomez-Pinedo

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Guest Editor

Laboratory of Neurosciences, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, 28040 Madrid, Spain
Interests: neurogenesis; oligodendroglia; demyelinating diseases; subventricular zone; neural repair; cell therapy

Prof. Dr. Oscar Gonzalez-Perez

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Guest Editor

Faculty of Psychology, University of Colima, Colima 28040, Mexico
Interests: neurogenesis; oligodendroglia; demyelinating diseases; subventricular zone

Special Issue Information

Dear Colleagues,

In the last 30 years, the therapeutic developments in multiple sclerosis (MS) have been incessant and we already have a large number of drugs that have changed the natural history of the disease. These drugs are intended to modify the inflammatory mechanisms that occur, but have not directly addressed the repair of the damage that occurs. The pathological changes that occur in MS are marked by inflammation, demyelination–remyelination, and neurodegeneration. Both primary and adaptive biological remyelination are altered in patients, but the alteration in remyelination is greater in response to demyelination. In recent years, different groups have advanced the understanding of the mechanisms that lead to remyelination, as well as possible therapeutic targets that may favor its occurrence in MS patients, but the understanding of the process is still inadequate. Different drugs are already being tested which act on these targets, and many researchers consider that the action on demyelination–remyelination is the next step in MS research. Many questions are still open regarding the mechanisms of remyelination, the experimental models for research directed to this mechanism, the diagnostic methods focused on being able to analyze the presence and degree of remyelination, the designs of clinical trials to be able to evaluate these drugs, and regarding the consequences they can have on patient quality of life. This Special Issue aims to review the state-of-the-art of research on remyelination in MS, including mechanisms, directed research models, diagnosis, and therapeutic research.

Prof. Dr. Jorge Matias-Guiu
Dr. Ulises Gomez-Pinedo
Prof. Dr. Oscar Gonzalez-Perez
Guest Editors

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Keywords

multiple sclerosis
remyelination
repair
therapy

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Published Papers (4 papers)

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Research

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23 pages, 10265 KiB

Open AccessArticle

Delayed Maturation of Oligodendrocyte Progenitors by Microgravity: Implications for Multiple Sclerosis and Space Flight

by Victoria Tran, Nicholas Carpo, Sophia Shaka, Joile Zamudio, Sungshin Choi, Carlos Cepeda and Araceli Espinosa-Jeffrey

Life 2022, 12(6), 797; https://doi.org/10.3390/life12060797 - 27 May 2022

Cited by 5 | Viewed by 2870 | Correction

Abstract

In previous studies, we examined the effects of space microgravity on human neural stem cells. To date, there are no studies on a different type of cell that is critical for myelination and electrical signals transmission, oligodendrocyte progenitors (OLPs). The purpose of the present study was to examine the behavior of space-flown OLPs (SPC-OLPs) as they were adapting to Earth’s gravity. We found that SPC-OLPs survived, and most of them proliferated normally. Nonetheless, some of them displayed incomplete cytokinesis. Both morphological and ontogenetic analyses showed that they remained healthy and expressed the immature OLP markers Sox2, PDGFR-α, and transferrin (Tf) after space flight, which confirmed that SPC-OLPs displayed a more immature phenotype than their ground control (GC) counterparts. In contrast, GC OLPs expressed markers that usually appear later (GPDH, O4, and ferritin), indicating a delay in SPC-OLPs’ development. These cells remained immature even after treatment with culture media designed to support oligodendrocyte (OL) maturation. The most remarkable and surprising finding was that the iron carrier glycoprotein Tf, previously described as an early marker for OLPs, was expressed ectopically in the nucleus of all SPC-OLPs. In contrast, their GC counterparts expressed it exclusively in the cytoplasm, as previously described. In addition, analysis of the secretome demonstrated that SPC-OLPs contained 3.5 times more Tf than that of GC cells, indicating that Tf is gravitationally regulated, opening two main fields of study to understand the upregulation of the Tf gene and secretion of the protein that keep OLPs at a progenitor stage rather than moving forward to more mature phenotypes. Alternatively, because Tf is an autocrine and paracrine factor in the central nervous system (CNS), in the absence of neurons, it accumulated in the secretome collected after space flight. We conclude that microgravity is becoming a novel platform to study why in some myelin disorders OLPs are present but do not mature. Full article

(This article belongs to the Special Issue Multiple Sclerosis: Research in Remyelination, the Next Step)

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Review

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19 pages, 1249 KiB

Open AccessEditor’s ChoiceReview

Exosomes and Biomaterials: In Search of a New Therapeutic Strategy for Multiple Sclerosis

by Doddy Denise Ojeda-Hernández, Mercedes A. Hernández-Sapiéns, Edwin E. Reza-Zaldívar, Alejandro Canales-Aguirre, Jordi A. Matías-Guiu, Jorge Matías-Guiu, Juan Carlos Mateos-Díaz, Ulises Gómez-Pinedo and Francisco Sancho-Bielsa

Life 2022, 12(9), 1417; https://doi.org/10.3390/life12091417 - 11 Sep 2022

Cited by 10 | Viewed by 4195

Abstract

Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited its application. A series of recent studies have focused on the cell secretome, showing it to provide the most benefits of cell therapy. Exosomes are a key component of the cell secretome, participating in the transfer of bioactive molecules. These nano-sized vesicles offer many therapeutical advantages, such as the capacity to cross the blood-brain barrier, an enrichable cargo, and a customizable membrane. Moreover, integrating of biomaterials into exosome therapy could lead to new tissue-specific therapeutic strategies. In this work, the use of exosomes and their integration with biomaterials is presented as a novel strategy in the treatment of MS. Full article

(This article belongs to the Special Issue Multiple Sclerosis: Research in Remyelination, the Next Step)

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11 pages, 1123 KiB

Open AccessReview

The Integration of Cell Therapy and Biomaterials as Treatment Strategies for Remyelination

by Eneritz López-Muguruza, Natalia Villar-Gómez, Jordi A. Matias-Guiu, Belen Selma-Calvo, Lidia Moreno-Jiménez, Francisco Sancho-Bielsa, Juan Lopez-Carbonero, María Soledad Benito-Martín, Silvia García-Flores, Natalia Bonel-García, Ola Mohamed-Fathy Kamal, Denise Ojeda-Hernández, Jorge Matías-Guiu and Ulises Gómez-Pinedo

Life 2022, 12(4), 474; https://doi.org/10.3390/life12040474 - 24 Mar 2022

Cited by 7 | Viewed by 3404

Abstract

Multiple sclerosis (MS) is a chronic degenerative autoimmune disease of the central nervous system that causes inflammation, demyelinating lesions, and axonal damage and is associated with a high rate of early-onset disability. Disease-modifying therapies are used to mitigate the inflammatory process in MS but do not promote regeneration or remyelination; cell therapy may play an important role in these processes, modulating inflammation and promoting the repopulation of oligodendrocytes, which are responsible for myelin repair. The development of genetic engineering has led to the emergence of stable, biocompatible biomaterials that may promote a favorable environment for exogenous cells. This review summarizes the available evidence about the effects of transplantation of different types of stem cells reported in studies with several animal models of MS and clinical trials in human patients. We also address the advantages of combining cell therapy with biomaterials. Full article

(This article belongs to the Special Issue Multiple Sclerosis: Research in Remyelination, the Next Step)

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