Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations
Language English Country United States Media print
Document type Journal Article
PubMed
27866327
DOI
10.1007/s12015-016-9703-3
PII: 10.1007/s12015-016-9703-3
Knihovny.cz E-resources
- Keywords
- Immunomodulation, Immunosuppressive drugs, Mesenchymal stem cells, Stem cell therapy, T cells,
- MeSH
- Lymphocyte Activation drug effects immunology MeSH
- Cyclosporine pharmacology MeSH
- Cytokines metabolism MeSH
- Dexamethasone pharmacology MeSH
- Glucocorticoids pharmacology MeSH
- Immunosuppressive Agents pharmacology MeSH
- Coculture Techniques MeSH
- Cells, Cultured MeSH
- Mycophenolic Acid pharmacology MeSH
- Mesenchymal Stem Cells cytology immunology metabolism MeSH
- Mice, Inbred BALB C MeSH
- Prednisone pharmacology MeSH
- Cell Proliferation drug effects MeSH
- Flow Cytometry MeSH
- Sirolimus pharmacology MeSH
- T-Lymphocyte Subsets cytology drug effects immunology MeSH
- Mesenchymal Stem Cell Transplantation methods MeSH
- Cell Survival drug effects MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cyclosporine MeSH
- Cytokines MeSH
- Dexamethasone MeSH
- Glucocorticoids MeSH
- Immunosuppressive Agents MeSH
- Mycophenolic Acid MeSH
- Prednisone MeSH
- Sirolimus MeSH
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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