Study of mesenchymal stem cell and lymphocytes interactions using the graft vesus host desease model.

Abstract

A major complication and limitation to the broad application of hematopoietic stem cell transplantation (HSCT) is graft-versushost disease (GvHD), which results from immune-mediated attack of recipient tissue by donor T cells contained in the transplant. GvHD accounts for 15-30% of deaths that occur following allogeneic HSCT (Ferrara et al., 2009). Despite recent advances to reduce the incidence of GvHD through altering prophylactic regimens and reducing the intensity of conditioning prior to transplantation, effective treatments for GvHD are lacking (Bleakley e Riddell, 2004;. Ringden et al, 2009). More recently, the immune regulatory potential of MSCs has been focused on, MSCs have been found to supress inflammation by inhibiting T cell p´roliferation, representing a novel treatment for GVHD. Le Blanc et al described a patient with severe GVHD who was infused with MSCs in 2004, his GVHD improved dramatically following 2 infusions, and no significant side effects occurred. In a multicenter phase II study by the European Group for the Blood and Marrow Transplantation, the response rate to treatment of GVHD with MSCs was over 70%, and treatment efficiency was not related to a donor human leukocyte antigen (HLA) match (Le Blanc, 2008). Upon this knowledge, we want to investigate the action of mesenchymal cells in lymphocytes, by determining the expression of transcription factors linked to Th differentiation, the expression of some genes involved in the process of lymphocyte response and assess their activation profile.