Influencia de productos solubles de células madre mesenquimales de decidua sobre la actividad de linfocitos T CD4+ de fenotipo definido

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease due to an autoimmune response, the most commonly used experimental model for this human pathology is experimental autoimmune encephalomyelitis (EAE), which shares similar pathological features with multiple sclerosis. Among all the immune cells that participate in the pathogenesis, T CD4+ lymphocytes play a crucial role, as they become autoreactive to myelin self-antigens and initiate the inflammatory cascade in the central nervous system (CNS). Several pharmacological immunomodulatory therapies are available, but these drugs do not provide a definitive cure. This fact, leads to the necessity of searching new therapeutic strategies. Cellular therapies using mesenchymal stem cells (MSCs) derived from different sources, are believed to be an interesting alternative owing to its immunomodulatory and neuroprotective effects that have been reported in EAE. This study aims to explore if soluble factors released by decidua derived mesenchymal stem cells (DMSCs) are able to influence the activity of mature T CD4+ cells, including the proinflammatory, Th1 and Th17, and the anti-inflammatory, Th2 and Treg, subsets. For this purpose, CD4+ cells were isolated and differentiated into the mentioned T subsets and were treated with conditioned medium; the supernatant of DMSCs cultures. Results show, on the one hand, that soluble factors do not affect Th17 or Th2 marker cytokines, but they do increase the production of IFN-g by Th1 subset and the expression of Foxp3 and IL- 10 genes by Tregs. On the other hand, conditioned medium increases proliferative response in every subset. These results suggest that DMSCs soluble factors might act differentially on fullypolarized T CD4+ cytokine profiles but equally on their proliferation and that DMSCs secretome might have a therapeutic potential in EAE model increasing Treg response.