This thesis encompasses an overview of publications examining interactions of mesenchymal stem cells (MSC) with the immune system, the induction of an immunosuppressive phenotype by MSC stimulation and clinical applications of MSC. We present the results of in vitro MSC stimulation with different activating factors (AD) and supernatants from mixed lymphocyte reactions (MLR). The aim was to evaluate which AD and MLR supernatants induce an immunosuppressive phenotype in MSC, and to compare them. The induction of an immunosuppressive phenotype was determined by enhanced expression of PD-L1 and IDO, and the increased immunogenicity was determined by expression of HLA-DR. The best combinations of AD were rapamycin/MPLA/TNFα/IFNγ for inducing expression of PD-L1, and the combinations rapamycin/TNFα/IFNγ and MPLA/TNFα/IFNγ for inducing expression of IDO. These combinations of AD also did not induce higher expression of HLA-DR. The immunosuppressive phenotype induction by these combinations of AD might be caused by their synergistic or additive behaviour. To our knowledge this is the first publication of MSC stimulation with these combinations of AD. The MLR supernatants best at inducing an immunosuppressive phenotype were those that took place in media with added MPLA, which strengthens the immune response. MLR supernatants achieved similar results as AD and could be a potential alternative to MSC stimulation with AD.
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