Artikel
Interactions between mesenchymal stem cells, immunosuppressive drugs and T-cells in preclinical transplantation models
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Veröffentlicht: | 20. Mai 2011 |
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Gliederung
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Introduction: Mesenchymal stem cells (MSC) are known to have an immunosuppressive effect in vitro as well as in vivo. Sufficient priming by proinflammatory cytokines, as caused by activated T cells, is necessary for this MSC function. T-cell activation, however, can be inhibited by immunosuppressive drugs (ISD). Here, we investigate the effect of MSC interacting with different ISD in two murine transplant models.
Materials and methods: MSC were cultured under standard conditions. CFSE-labeled B6-splenocytes were injected into C3B6 F1 animals, and proliferation was monitored by flow-cytometry. In the second model C3H hearts were grafted into B6 recipients. In both models we applied different combinations of MSC and ISD.
Results: T cell proliferation was suppressed by all drugs depending on the dose. The combination of MSC and mycophenloic acid (MPA) showed an increased T cell suppression in vivo as well as prolonged allograft survival. However, the combination of MSC and ciclosporin or sirolimus had no additional effect. Further in vitro studies revealed a correlation between the impact of ISD on IFN-gamma production and the additional immunosuppressive ability of MSC.
Conclusion: MSC can affect T-cell proliferation, but there is a bidirectional relationship between MSC function and T-cell response. Since MSC only have an additional immunosuppressive effect when combined with ISD, we outline that pharmacological inhibition of T-cells also affects the outcome of combined MSC-ISD treatment. According to this finding only ISD allowing T-cell activation should be used in MSC combined treatment, which has great impact on MSC biology and further medical applications.