Influence of oligodendrocyte-derived exosomes on cell therapy of experimental autoimmune encephalomyelitis

• Grant number: 21/09869-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2022
• End date: February 29, 2024
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Carlos Eduardo Ambrósio
• Grantee: Sarah Ingrid Pinto Santos
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil

Abstract

Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by the autoimmune destruction of the myelin sheath that leads the patient to irreversible and progressive functional deficits. Preclinical studies using neural stem cells have already shown their potential in neuronal regeneration and remyelination. However, the use of cell therapy alone has not yet been sufficient to reach satisfactory therapeutic levels. Considering these limitations, there is a need to associate cell therapy with other coadjuvant protocols. In this context, extracellular vesicles may contribute to intercellular communication, stimulating the production of remyelinating proteins and lipids, and providing trophic support to axons. In view of this, this research project aims to evaluate the therapeutic efficacy of the association between neural stem cells and oligodendrocyte-derived extracellular vesicles in an animal model of multiple sclerosis. To this end, the project will be carried out in three experimental phases. In phase 1, neural stem cells will be isolated and cultured from two distinct regions of the central nervous system. Gene expression analysis by RT-qPCR will determine the most appropriate cell source for phase 2. In phase 2 the neural stem cells will be differentiated into oligodendrocytes, the extracellular vesicles will be isolated by ultracentrifugation and characterized using the protein detection method by Western Blotting. Phase 3 consists in the execution of the therapeutic protocols in 20 C57BL/6 mice that will be distributed in groups according to the established protocol. The treatments will be clinically evaluated by scores and microscopically evaluated by histology and immunohistochemistry. With this study we hope to obtain an efficient therapeutic protocol and a better understanding of the role of exosomes as possible adjuvants in cell therapy.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANTOS, Sarah Ingrid Pinto. Influence of oligodendrocyte precursor cell-derived exosomes on cell therapy of experimental autoimmune encephalomyelitis. 2024. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Zootecnica e Engenharia de Alimentos (FZE/BT) Pirassununga.