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128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

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Interactions between mesenchymal stem cells, immunosuppressive drugs and T-cells in preclinical transplantation models

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  • Yorick Soeder - Uniklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg
  • Philipp Renner - Uniklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg
  • Elke Eggenhofer - Uniklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg
  • Felix Popp - Uniklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg
  • Edward Geissler - Uniklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg
  • Hans Jürgen Schlitt - Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg
  • Marc-Hendrik Dahlke - Uniklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch436

doi: 10.3205/11dgch436, urn:nbn:de:0183-11dgch4362

Published: May 20, 2011

© 2011 Soeder et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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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.