Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články
PubMed
27866327
DOI
10.1007/s12015-016-9703-3
PII: 10.1007/s12015-016-9703-3
Knihovny.cz E-zdroje
- Klíčová slova
- Immunomodulation, Immunosuppressive drugs, Mesenchymal stem cells, Stem cell therapy, T cells,
- MeSH
- aktivace lymfocytů účinky léků imunologie MeSH
- cyklosporin farmakologie MeSH
- cytokiny metabolismus MeSH
- dexamethason farmakologie MeSH
- glukokortikoidy farmakologie MeSH
- imunosupresiva farmakologie MeSH
- kokultivační techniky MeSH
- kultivované buňky MeSH
- kyselina mykofenolová farmakologie MeSH
- mezenchymální kmenové buňky cytologie imunologie metabolismus MeSH
- myši inbrední BALB C MeSH
- prednison farmakologie MeSH
- proliferace buněk účinky léků MeSH
- průtoková cytometrie MeSH
- sirolimus farmakologie MeSH
- T-lymfocyty - podskupiny cytologie účinky léků imunologie MeSH
- transplantace mezenchymálních kmenových buněk metody MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cyklosporin MeSH
- cytokiny MeSH
- dexamethason MeSH
- glukokortikoidy MeSH
- imunosupresiva MeSH
- kyselina mykofenolová MeSH
- prednison 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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