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A local application of mesenchymal stem cells and cyclosporine A attenuates immune response by a switch in macrophage phenotype
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SYSNO ASEP 0454064 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title A local application of mesenchymal stem cells and cyclosporine A attenuates immune response by a switch in macrophage phenotype Author(s) Hájková, M. (CZ)
Javorková, Eliška (UEM-P) RID
Zajícová, Alena (UEM-P) RID
Trošan, Peter (UEM-P)
Holáň, Vladimír (UEM-P) RID
Krulová, Magdaléna (UEM-P)Number of authors 6 Source Title Journal of Tissue Engineering and Regenerative Medicine. - : Wiley - ISSN 1932-6254
Roč. 11, č. 5 (2017), s. 1456-1465Number of pages 10 s. Language eng - English Country GB - United Kingdom Keywords mesenchymal stem cells ; cyclosporine A ; macrophages Subject RIV EB - Genetics ; Molecular Biology OECD category Cell biology R&D Projects GAP304/11/0653 GA ČR - Czech Science Foundation (CSF) GAP301/11/1568 GA ČR - Czech Science Foundation (CSF) GA14-12580S GA ČR - Czech Science Foundation (CSF) NT14102 GA MZd - Ministry of Health (MZ) Institutional support UEM-P - RVO:68378041 UT WOS 000402987500013 EID SCOPUS 84933574461 DOI 10.1002/term.2044 Annotation The immunosuppressive effects of systemically administered mesenchymal stem cells (MSCs) and immunosuppressive drugs have been well documented. We analysed the mechanisms underlying the therapeutic effect of MSCs applied locally in combination with non-specific immunosuppression in a mouse model of allogeneic skin transplantation. The MSC-seeded and cyclosporine A (CsA)-loaded nanofibre scaffolds were applied topically to skin allografts in a mouse model and the local immune response was assessed and characterized. MSCs migrated from the scaffold into the side of injury and were detected in the graft region and draining lymph nodes (DLNs). The numbers of graft-infiltrating macrophages and the production of nitric oxide (NO) were significantly decreased in recipients treated with MSCs and CsA, and this reduction correlated with impaired production of IFN. in the graft and DLNs. In contrast, the proportion of alternatively activated macrophages (F4/80(+)CD206(+) cells) and the production of IL-10 by intragraft macrophages were significantly upregulated. The ability of MSCs to alter the phenotype of macrophages from the M1 type into an M2 population was confirmed in a co-culture system in vitro. We suggest that the topical application of MSCs in combination with CsA induces a switch in macrophages to a population with an alternatively activated 'healing' phenotype and producing elevated levels of IL-10. These alterations in macrophage phenotype and function could represent one of the mechanisms of immunosuppressive action of MSCs applied in combination with CsA. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2018
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