Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F17%3A00476434" target="_blank" >RIV/68378041:_____/17:00476434 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/17:10366569

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s12015-016-9703-3" target="_blank" >http://dx.doi.org/10.1007/s12015-016-9703-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12015-016-9703-3" target="_blank" >10.1007/s12015-016-9703-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations

Popis výsledku v původním jazyce

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 (ROR gamma t(+)), Th1 (T-bet(+)), Th2 (GATA-3(+)) and Treg (Foxp3(+)) cell proportion and on the production of corresponding key cytokines (IL-17, IFN gamma,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.

Název v anglickém jazyce

Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations

Popis výsledku anglicky

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 (ROR gamma t(+)), Th1 (T-bet(+)), Th2 (GATA-3(+)) and Treg (Foxp3(+)) cell proportion and on the production of corresponding key cytokines (IL-17, IFN gamma,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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Stem Cell Reviews and Reports

ISSN

1550-8943

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

104-115

Kód UT WoS článku

000397212100015

EID výsledku v databázi Scopus

2-s2.0-84995810953