Therapy with exosomes produced by human embryonic stem cells (hESCs) that overexpress FGF2 on the course of Experimental Autoimmune Encephalomyelitis (EAE) in C57BLJ/6J mice

• Grant number: 23/15760-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2024
• End date: July 31, 2027
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Santiago José Ortiz Peñuela
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination, axonal loss and neurodegeneration. Treatment for patients with MS is carried out using immunomodulators and immunosuppressants, seeking to reduce the risk of new outbreaks and the progression of neurological disability. The Experimental Autoimmune Encephalomyelitis (EAE) model is used to study the mechanisms that lead to the events that occur in MS and its use has been promoted in the development of treatment strategies. Currently, treatment with derivatives of embryonic stem cells (hESCs) constitutes a new therapeutic strategy, with emphasis on extracellular vesicles (EVs) that contain various substances such as growth factors. Furthermore, FGF2 has been shown to increase neuronal survival, protect neurons against excitotoxicity, decrease cell death by apoptosis and promote the regeneration of myelinated axons. Thus, the present work aims to evaluate the possible immunomodulatory and neuroprotective effect of FGF2 in the EAE model in C57BL/6J mice, in parallel to therapy with exosomes of hESCs that overexpress FGF2. The therapy will be applied through intraperitoneal (IP) injection after induction of EAE, and the results will be analyzed after the first remission of the disease using a multidisciplinary approach, combining immunohistochemistry for glial reactivity, synaptic and myelin preservation. In addition, the inflammatory profile of glial cells and immune system cells will be analyzed using flow cytometry. We will also perform RT-qPCR to evaluate the levels of gene transcripts for anti-inflammatory (TGF², IL-4, IL-10) and pro-inflammatory (IL1², IL-6 and TNF-±) cytokines, in addition to synaptic analysis of neurons medullary motors by transmission electron microscopy.