Licensing by Inflammatory Cytokines Abolishes Heterogeneity of Immunosuppressive Function of Mesenchymal Stem Cell Population

When mesenchymal stem cells (MSCs) are used for therapy of immunological pathologies, they get into an inflammatory environment, altering the effectiveness of the treatment. To establish the impact of environmental inflammatory factors on MSCs' immunofunction in the mirror of intrinsic heteroge...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Szabó Enikő
Fajka-Boja Roberta
Kriston-Pál Éva
Hornung Ákos
Makra Ildikó
Katona Róbert László
Monostori Éva
Czibula Ágnes
Dokumentumtípus: Cikk
Megjelent: 2015
Sorozat:STEM CELLS AND DEVELOPMENT 24 No. 18
doi:10.1089/scd.2014.0581

mtmt:2946565
Online Access:http://publicatio.bibl.u-szeged.hu/8846
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520 3 |a When mesenchymal stem cells (MSCs) are used for therapy of immunological pathologies, they get into an inflammatory environment, altering the effectiveness of the treatment. To establish the impact of environmental inflammatory factors on MSCs' immunofunction in the mirror of intrinsic heterogeneity of mouse MSC population, individual MSC clones were generated and characterized. Adipogenic but not osteogenic differentiation and pro-angiogenic activity of five independent MSC cell lines were similar. Regarding osteogenic differentiation, clones MSC3 and MSC6 exhibited poorer capacity than MSC2, MSC4, and MSC5. To study the immunosuppressive heterogeneity, in vitro and in vivo experiments have been carried out using T-cell proliferation assay and delayed-type hypersensitivity (DTH) response, respectively. A remarkable difference was found between the clones in their ability to inhibit T-cell proliferation in the following order: MSC2MSC5>MSC4>MSC3>>MSC6. Nevertheless, the differences between the immunosuppressive activities of the individual clones disappeared on pretreatment of the cells with pro-inflammatory cytokines, a procedure called licensing. Stimulation of all clones with IFN- and TNF- resulted in elevation of their inhibitory capability to a similar level. Nitric oxide (NO) and prostaglandin E2 (PGE2) were identified as major mediators of immunofunction of the MSC clones. The earlier findings were also supported by in vivo results. Without licensing, MSC2 inhibited DTH response, while MSC6 did not affect DTH response. In contrast, prestimulation of MSC6 with inflammatory cytokines resulted in strong suppression by this clone as well. Here, we have showed that MSC population is functionally heterogeneous in terms of immunosuppressive function; however, this variability is largely reduced under pro-inflammatory conditions. 
700 0 2 |a Fajka-Boja Roberta  |e aut 
700 0 2 |a Kriston-Pál Éva  |e aut 
700 0 2 |a Hornung Ákos  |e aut 
700 0 2 |a Makra Ildikó  |e aut 
700 0 2 |a Katona Róbert László  |e aut 
700 0 2 |a Monostori Éva  |e aut 
700 0 2 |a Czibula Ágnes  |e aut 
700 0 2 |a Katona Róbert László  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/8846/1/Licensing_by_Inflammatory_Cytokines_Abolishes_u.pdf  |z Dokumentum-elérés