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ORIGINAL RESEARCH article

Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 18 - 2024 | doi: 10.3389/fncel.2024.1413843
This article is part of the Research Topic Oligodendroglia Biology and Pathology: Myelination and Beyond View all articles

Oligodendrocyte precursor cell-derived exosomes combined with cell therapy promote clinical recovery by immunomodulation and gliosis attenuation

Provisionally accepted
Sarah I. Santos Sarah I. Santos 1*Santiago J. Peñuela Santiago J. Peñuela 2Alessandro de Paula Filho Alessandro de Paula Filho 1Ana Laura Midori Rossi Tomiyama Ana Laura Midori Rossi Tomiyama 2Lilian D. Coser Lilian D. Coser 2Juliano C. Da Silveira Juliano C. Da Silveira 1Daniele Dos Santos Martins Daniele Dos Santos Martins 1Adriano P. Ciena Adriano P. Ciena 3Alexandre L. Oliveira Alexandre L. Oliveira 2Carlos E. Ambrósio Carlos E. Ambrósio 1
  • 1 University of São Paulo, São Paulo, Brazil
  • 2 State University of Campinas, Campinas, São Paulo, Brazil
  • 3 São Paulo State University, Campus Rio Claro, Rio Claro, São Paulo, Brazil

The final, formatted version of the article will be published soon.

    Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by autoimmune destruction of the myelin sheath, leading to irreversible and progressive functional deficits in patients. Pre-clinical studies involving the use of neural stem cells (NSCs) have already demonstrated their potential in neuronal regeneration and remyelination. However, the exclusive application of cell therapy has not proved sufficient to achieve satisfactory therapeutic levels. Recognizing these limitations, there is a need to combine cell therapy with other adjuvant protocols. In this context, extracellular vesicles (EVs) can contribute to intercellular communication, stimulating the production of proteins and lipids associated with remyelination and providing trophic support to axons. This study aimed to evaluate the therapeutic efficacy of the combination of NSCs and EVs derived from oligodendrocyte precursor cells (OPCs) in an animal model of multiple sclerosis. OPCs were differentiated from NSCs and had their identity confirmed by gene expression analysis and immunocytochemistry. Exosomes were isolated by differential ultracentrifugation and characterized by Western, transmission electron microscopy and nanoparticle tracking analysis. Experimental therapy of C57BL/6 mice induced with experimental autoimmune encephalomyelitis (EAE) were grouped in control, treated with NSCs, treated with OPC-derived EVs and treated with a combination of both. The treatments were evaluated clinically using scores and body weight, microscopically using immunohistochemistry and immunological profile by flow cytometry. The animals showed significant clinical improvement and weight gain with the treatments. However, only the treatments involving EVs led to immune modulation, changing the profile from Th1 to Th2 lymphocytes. 15 days after treatment revealed a reduction in reactive microgliosis and astrogliosis in the groups treated with EVs. However, there was no reduction in demyelination. The results indicate the potential therapeutic use of OPC-derived EVs to attenuate inflammation and promote recovery in EAE, especially when combined with cell therapy.

    Keywords: extracellular vesicles, Multiple Sclerosis, neural stem cell, neurodegeneration, Immunomodulation, oligodendrocyte precursor cell

    Received: 08 Apr 2024; Accepted: 13 Jun 2024.

    Copyright: © 2024 Santos, Peñuela, de Paula Filho, Tomiyama, Coser, Da Silveira, Martins, Ciena, Oliveira and Ambrósio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sarah I. Santos, University of São Paulo, São Paulo, Brazil

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.