Cyclosporine A promotes the therapeutic effect of mesenchymal stem cells on transplantation reaction
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F19%3A10409292" target="_blank" >RIV/00216208:11310/19:10409292 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=0SQr5dnLwn" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=0SQr5dnLwn</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1042/CS20190294" target="_blank" >10.1042/CS20190294</a>
Alternative languages
Result language
angličtina
Original language name
Cyclosporine A promotes the therapeutic effect of mesenchymal stem cells on transplantation reaction
Original language description
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 8 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-ber and CD4(+)ROR gamma t(+) 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 o f therapy.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Clinical Science
ISSN
0143-5221
e-ISSN
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Volume of the periodical
133
Issue of the periodical within the volume
21
Country of publishing house
GB - UNITED KINGDOM
Number of pages
15
Pages from-to
2143-2157
UT code for WoS article
000511197800002
EID of the result in the Scopus database
2-s2.0-85074676167