Estabelecimento de metodologia de diferenciação de células tronco embrionárias de camundongo em células precursoras de oligodendrócitos: uma plataforma para triagem de novas drogas remielinizantes

Abstract

The myelin sheath plays a crucial role in nerve function. In the Central Nervous System, the myelin sheath is produced by oligodendrocytes (OL), which are differentiated from oligodendrocyte precursor cells (OPC). Several neurological disorders, including multiple sclerosis, display damage in the myelin sheath and failure in the remyelination. Therefore, researching for new compounds that act in the OPCs differentiation to OLs is a promising strategy to treat demyelinating diseases. In this study, we established a methodology that allows the generation of OPCs in large quantities from two lineages of mouse embryonic stem cells (mESCs; lineages HM-1 and USP-1). Initially, mESCs were induced to differentiate into neural precursors and, later, to OPCs by adding growth factors such as FGF, EGF and PDGF. The characteristic and predominant expression of Olig2, Sox-10, PDGFRα and NG2 observed by immunofluorescence, and the double labeling of PDGFRα and NG2 by flow cytometry, confirmed the OPCs generation from mESCs. Therefore, this study shows an efficient and reproducible methodology for generating OPCs capable of being used in screening assays or in OLs lineage biology studies.