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- Title
Toll-like receptor triggering in cord blood mesenchymal stem cells.
- Authors
van den Berk, Lieke C. J.; Jansen, Bastiaan J. H.; Siebers-Vermeulen, Kim G. C.; Netea, Mihai G.; Latuhihin, Talia; Bergevoet, Saskia; Raymakers, Reinier A.; Kögler, Gesine; Figdor, Carl C.; Adema, Gosse J.; Torensma, Ruurd
- Abstract
Recently, the antagonizing effect on the differentiation of mesenchymal stem cells (MSCs) by toll-like receptor (TLR) ligands, was described. Our study shows that on more primitive cord blood derived MSCs, the expression of TLRs and ligand-induced triggering differs from that of bone marrow derived MSCs. At the RNA level, cord blood MSCs (unrestricted somatic stem cells; USSCs) express low levels of TLR1,3,5,9 and high levels of TLR4 and TLR6. At the protein level expression of TLR5 and very low expression of TLR4 was observed. NF-κB translocation studies revealed that both TLR4 and TLR5 are functional, although signalling kinetics induced by the individual ligands differed. Stimulation of USSCs with either lipopolysaccharide (LPS) or flagellin resulted in a marked increase of interleukin (IL)-6 and/or IL-8 production although levels differed significantly between both stimuli. Interestingly, tumour necrosis factor (TNF)-α was undetectable after TLR stimulation, which appeared to be due to an inactivated TNF-α promoter in USSCs. Moreover, osteoblastic differentiation was enhanced after triggering USSCs with LPS and flagellin. In summary, TLR4 and 5 signalling in USSCs is slow and results in the up-regulation of a restricted number of pro-inflammatory cytokines and enhanced osteoblastic differentiation. Apparently, the outcome of TLR signalling depends on the cell type that expresses them.
- Subjects
BONE marrow blood-vessels; STEM cells; CELLULAR immunity; IMMUNOREGULATION; TUMOR necrosis factors
- Publication
Journal of Cellular & Molecular Medicine, 2009, Vol 13, Issue 9b, p3415
- ISSN
1582-1838
- Publication type
Article
- DOI
10.1111/j.1582-4934.2008.00653.x