Imunomodulação promovida pelo transplante de células tronco mesenquimais derivadas de medula óssea em lesões no sistema nervoso central

• Autor(a) principal: Galindo, Layla Testa [UNIFESP]
• Data de Publicação: 2011
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/00130000190pb
• Texto Completo: http://repositorio.unifesp.br/handle/11600/9734
• topic: Células tronco mesenquimais; Citocinas; Células tronco-neurais; Imunomodulação; Sistema nervoso central/lesões; Camundongos Endogâmicos C57BL; Immunomodulation; Central nervous system//injuries; Inbred mice C57BL; Mesenchymal stromal cells; Cytokines; Neural stem cells

Central nervous system (CNS) injury breakes the impermeability of the blood brain barrier, this allows the invasion of immune cells and activation of glial cells, mainly microglia and astrocytes. This process triggers the secretion of inflammatory mediators by these cells. Cytokines are the main molecules in neuroinflammatory response and are critical for its regulation, exerting a variety of actions in the CNS. Furthermore, mesenchymal stem cells (MSC) which have proliferative potential and are able to originate different and specialized cell lineages, also secrete these molecules, characterizing its immunomodulatory function. MSC, particularly those derived from bone marrow, promote tissue repair by secreting factors that enhance tissue regeneration stimulating proliferation, migration and differentiation of endogenous stem-like progenitors found in most tissues, decreasing inflammatory and immune reactions and apoptosis. The ability of such cells to alter tissue microenvironment through its trophic influence may contribute more significantly than their capacity for transdifferentiation in effecting tissue repair.Our hypothesis is that MSC secreted cytokines could take part in the attraction of endogenous neural stem cells (NSC) to an injury site in the CNS, providing a favorable microenvironment for these cells. Our aim was to study the effects of factors secreted by MSC on NSC in vitro and to analyse the MSC cytokines expression in vivo in a model of CNS traumatic injury. We first evaluated the effects of MSC secreted factors on apoptosis, proliferation and differentiation of adult NSC derived from the subventricular zone and cultured as neurospheres. Neurospheres were cultured in MSC conditioned medium (MSC-CM), which was obtained from bone marrow-derived MSC cultures. Besides a traumatic injury was performed at the primary motor cortex of mice and MSCs were injected at the injury site. Our results show that MSC secreted factors do not induce or prevent NSC apoptosis, increase NSC proliferation and induce bigger expression of GFAP gene in vitro, this could indicate a tendency of differentiation to astrocytes. In vivo experiments show that MSC injection at an acute model of injury diminishes pro-inflamatory cytokines in the injured tissue, suggesting that MSC secreted factors may modulate the inflammation at the injury site, which may be interest to the development favorable microenvironment for endogenous NSC and consequently repair of the injured tissue.