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Cyclosporine A promotes the therapeutic effect of mesenchymal stem cells on transplantation reaction

Identifikátory výsledku

  • Kód výsledku v 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>

  • Výsledek na webu

    <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>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    Cyclosporine A promotes the therapeutic effect of mesenchymal stem cells on transplantation reaction

  • Popis výsledku v původním jazyce

    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.

  • Název v anglickém jazyce

    Cyclosporine A promotes the therapeutic effect of mesenchymal stem cells on transplantation reaction

  • Popis výsledku anglicky

    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.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    10601 - Cell biology

Návaznosti výsledku

  • Projekt

  • Návaznosti

    S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Ostatní

  • Rok uplatnění

    2019

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název periodika

    Clinical Science

  • ISSN

    0143-5221

  • e-ISSN

  • Svazek periodika

    133

  • Číslo periodika v rámci svazku

    21

  • Stát vydavatele periodika

    GB - Spojené království Velké Británie a Severního Irska

  • Počet stran výsledku

    15

  • Strana od-do

    2143-2157

  • Kód UT WoS článku

    000511197800002

  • EID výsledku v databázi Scopus

    2-s2.0-85074676167