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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1422-1432. Prepublished online as a Blood First Edition Paper on October 12, 2006; DOI 10.1182/blood-2006-06-028704. This Article Full Text (PDF) All Versions of this Article: blood-2006-06-028704v1 109/4/1422    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pevsner-Fischer, M. Articles by Zipori, D. Search for Related Content PubMed PubMed Citation Articles by Pevsner-Fischer, M. Articles by Zipori, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 12, 2006 Accepted October 4, 2006 Toll-like receptors and their ligands control mesenchymal stem cell functions Meirav Pevsner-Fischer, Vered Morad, Michal Cohen-Sfady, Liat Rousso-Noori, Alexandra Zanin-Zhorov, Shmuel Cohen, Irun R Cohen, and Dov Zipori* Departments of Molecular Cell Biology and Immunology, Weizmann Institute of Science, Reovot, Israel Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel Department of Immunology, Weizmann Institute of Science, Rehovot, Israel Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel * Corresponding author; email: dov.zipori{at}weizmann.ac.il. Mesenchymal stem cells (MSC) are widespread in adult organisms and may be involved in tissue maintenance and repair, as well as in the regulation of hemopoiesis and immunological responses. Thus, it is important to discover the factors controlling MSC renewal and differentiation. Here we report that adult MSC express functional Toll-like receptors (TLR), confirmed by the responses of MSC to TLR ligands. Pam3Cys, a prototypic TLR-2 ligand, augmented interleukin-6 secretion by MSC, induced nuclear factor B (NF-B) translocation, reduced MSC basal motility and increased MSC proliferation. The hallmark of MSC function is their capacity to differentiate into several mesodermal lineages. We show herein that Pam3Cys inhibited MSC differentiation into osteogenic, adipogenic and chondrogenic cells while sparing their immunosuppressive effect. Our study therefore shows that a TLR ligand can antagonize MSC differentiation triggered by exogenous mediators and consequently maintains the cells in an undifferentiated and proliferating state in vitro. Moreover, MSC derived from myeloid factor 88 (MyD88) deficient mice lacked the capacity to differentiate effectively into osteogenic and chondrogenic cells. It appears that TLR and their ligands can serve as regulators of MSC proliferation and differentiation and might affect the maintenance of MSC multipotency. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G.-Y. Chen, H.-C. Shiah, H.-J. Su, C.-Y. Chen, Y.-J. Chuang, W.-H. Lo, J.-L. Huang, C.-K. Chuang, S.-M. Hwang, and Y.-C. Hu Baculovirus Transduction of Mesenchymal Stem Cells Triggers the Toll-Like Receptor 3 Pathway J. Virol., October 15, 2009; 83(20): 10548 - 10556. [Abstract] [Full Text] [PDF] C. Bouffi, F. Djouad, M. Mathieu, D. Noel, and C. Jorgensen Multipotent mesenchymal stromal cells and rheumatoid arthritis: risk or benefit? Rheumatology, October 1, 2009; 48(10): 1185 - 1189. [Abstract] [Full Text] [PDF] R. Romieu-Mourez, M. Francois, M.-N. Boivin, M. Bouchentouf, D. E. Spaner, and J. Galipeau Cytokine Modulation of TLR Expression and Activation in Mesenchymal Stromal Cells Leads to a Proinflammatory Phenotype J. Immunol., June 15, 2009; 182(12): 7963 - 7973. [Abstract] [Full Text] [PDF] R. Covacu, L. Arvidsson, A. Andersson, M. Khademi, H. Erlandsson-Harris, R. A. Harris, M. A. Svensson, T. Olsson, and L. Brundin TLR Activation Induces TNF-{alpha} Production from Adult Neural Stem/Progenitor Cells J. Immunol., June 1, 2009; 182(11): 6889 - 6895. [Abstract] [Full Text] [PDF] D. J. Weiss, J. K. Kolls, L. A. Ortiz, A. Panoskaltsis-Mortari, and D. J. Prockop Stem Cells and Cell Therapies in Lung Biology and Lung Diseases Proceedings of the ATS, July 15, 2008; 5(5): 637 - 667. [Full Text] [PDF] N. Gupta, X. Su, B. Popov, J. W. Lee, V. Serikov, and M. A. Matthay Intrapulmonary Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Survival and Attenuates Endotoxin-Induced Acute Lung Injury in Mice J. Immunol., August 1, 2007; 179(3): 1855 - 1863. [Abstract] [Full Text] [PDF] J. Xu, C. R. Woods, A. L. Mora, R. Joodi, K. L. Brigham, S. Iyer, and M. Rojas Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L131 - L141. [Abstract] [Full Text] [PDF]

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