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Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations

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Abstract

Immunosuppressive drugs are widely used to treat undesirable immune reaction, however their clinical use is often limited by harmful side effects. The combined application of immunosuppressive agents with mesenchymal stem cells (MSCs) offers a promising alternative approach that enables the reduction of immunosuppressive agent doses and simultaneously maintains or improves the outcome of therapy. The present study aimed to determinate the effects of immunosuppressants on individual T cell subpopulations and to investigate the efficacy of MSC-based treatment combined with immunosuppressive drugs. We tested the effect of five widely used immunosuppressants with different action mechanisms: cyclosporine A, mycophenolate mofetil, rapamycin, and two glucocorticoids - prednisone and dexamethasone in combination with MSCs on mouse CD4+ and CD8+ lymphocyte viability and activation, Th17 (RORγt+), Th1 (T-bet+), Th2 (GATA-3+) and Treg (Foxp3+) cell proportion and on the production of corresponding key cytokines (IL-17, IFNγ, IL-4 and IL-10). We showed that MSCs modulate the actions of immunosuppressants and in combination with immunosuppressive drugs display distinct effect on cell activation and balance among different T lymphocytes subpopulations and exert a suppressive effect on proinflammatory T cell subsets while promoting the functions of anti-inflammatory Treg lymphocytes. The results indicated that MSC-based therapy could be a powerful strategy to attenuate the negative effects of immunosuppressive drugs on the immune system.

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Acknowledgements

This study was supported by grant 80815 from the Grant Agency of Charles University, the grant 14-12580S, and by the projects SVV 260310, UNCE 204013, NPU-I:LO1508 and NPU-I: LO1309 and P41-20504151.

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Authors and Affiliations

  1. Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 12843, Prague 2, Czech Republic

    Michaela Hajkova, Barbora Hermankova, Eliska Javorkova, Pavla Bohacova, Vladimir Holan & Magdalena Krulova

  2. Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic

    Michaela Hajkova, Barbora Hermankova, Eliska Javorkova, Pavla Bohacova, Alena Zajicova, Vladimir Holan & Magdalena Krulova

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  1. Michaela Hajkova
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Correspondence to Magdalena Krulova.

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Hajkova, M., Hermankova, B., Javorkova, E. et al. Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations. Stem Cell Rev and Rep 13, 104–115 (2017). https://doi.org/10.1007/s12015-016-9703-3

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