Therapeutic potential of cord blood plasma-derived extracellular vesicles in experimental autoimmune encephalomyelitis

• Grant number: 24/20971-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Sarah Ingrid Pinto Santos
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease that mainly affects young adults and is characterized by demyelination in the central nervous system, resulting in severe neurological symptoms. The pathology involves the action of immune cells that attack myelin, leading to various dysfunctions. Current treatment is based on immunosuppressive drugs which, although effective, can cause significant side effects. Recent research has focused on immunomodulation and cell therapy, including the use of stem cells and extracellular vesicles (EVs), which show promise in reducing inflammation and promoting remyelination. EVs, nanoparticles that facilitate cell communication, have advantages such as biocompatibility and the ability to cross biological barriers, making them ideal candidates for therapeutic applications. This research project aims to evaluate the therapeutic potential of human umbilical cord plasma-derived EVs (hEV-UCPs) in experimental autoimmune encephalomyelitis by investigating their effects and the miRNAs involved in the regulatory pathways. To this end, the proposed methodology aims to isolate hEV-UCPs by differential centrifugation and characterize them using nanoparticle tracking, transmission electron microscopy and Western blotting methods. RT-qPCR will also be used to analyze the expression of some miRNAs of interest in the treatment of neurodegenerative diseases. The therapeutic protocols will be carried out in three different phases. The first phase will determine the optimal therapeutic dose, the second phase will screen the EVs for biodistribution and target cells, and the third phase will evaluate the therapeutic effect at each stage of the disease. The C57BL/6 mice will be divided into 5 animals per group. The treatments will be evaluated clinically through scores, animal weight and functional gait analysis. Changes in nerve tissue will also be assessed by immunohistochemistry and flow cytometry. In the in vitro experiment, target cells will be supplemented with hEV-UCPs and evaluated by MTT assay and flow cytometry. With this study, we hope to understand the role of hEV-UCPs as a therapeutic tool in multiple sclerosis therapy. (AU)