Cyclosporine A promotes the therapeutic effect of mesenchymal stem cells on transplantation reaction
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31654074
DOI
10.1042/cs20190294
PII: 220846
Knihovny.cz E-resources
- Keywords
- Cyclosporine A, T-cells, immunomodulation, mesenchymal stem cell, rejection,
- MeSH
- Allografts drug effects immunology MeSH
- Cyclosporine pharmacology therapeutic use MeSH
- Cytokines metabolism MeSH
- Immunosuppressive Agents pharmacology therapeutic use MeSH
- Mice, Inbred BALB C MeSH
- Mice, Inbred C57BL MeSH
- Drug Evaluation, Preclinical MeSH
- Graft Survival drug effects immunology MeSH
- T-Lymphocytes drug effects metabolism MeSH
- Mesenchymal Stem Cell Transplantation * MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cyclosporine MeSH
- Cytokines MeSH
- Immunosuppressive Agents MeSH
The successful application of mesenchymal stem cells (MSCs) remains a major challenge in stem cell therapy. Currently, several in vitro studies have indicated potentially beneficial interactions of MSCs with immunosuppressive drugs. These interactions can be even more complex in vivo, and it is in this setting that we investigate the effect of MSCs in combination with Cyclosporine A (CsA) on transplantation reaction and allogeneic cell survival. Using an in vivo mouse model, we found that CsA significantly promoted the survival of MSCs in various organs and tissues of the recipients. In addition, compared to treatment with CsA or MSCs alone, the survival of transplanted allogeneic cells was significantly improved after the combined application of MSCs with CsA. We further observed that the combinatory treatment suppressed immune response to the alloantigen challenge and modulated the immune balance by harnessing proinflammatory CD4+T-bet+ and CD4+RORγt+ cell subsets. These changes were accompanied by a significant decrease in IL-17 production along with an elevated level of IL-10. Co-cultivation of purified naive CD4+ cells with peritoneal macrophages isolated from mice treated with MSCs and CsA revealed that MSC-educated macrophages play an important role in the immunomodulatory effect observed on distinct T-cell subpopulations. Taken together, our findings suggest that CsA promotes MSC survival in vivo and that the therapeutic efficacy of the combination of MSCs with CsA is superior to each monotherapy. This combinatory treatment thus represents a promising approach to reducing immunosuppressant dosage while maintaining or even improving the outcome of therapy.
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