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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 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 Citation Map 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. Related Collections Hematopoiesis and Stem Cells Signal Transduction Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Toll-like receptors and their ligands control mesenchymal stem cell functions Meirav Pevsner-Fischer1,2, Vered Morad1, Michal Cohen-Sfady2, Liat Rousso-Noori1, Alexandra Zanin-Zhorov2, Shmuel Cohen2, Irun R. Cohen2, and Dov Zipori1 1 Department of Molecular Cell Biology, the Weizmann Institute of Science, Rehovot, Israel; 2 Department of Immunology, the Weizmann Institute of Science, Rehovot, Israel Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be involved in tissue maintenance and repair as well as in the regulation of hematopoiesis and immunologic responses. Thus, it is important to discover the factors controlling MSC renewal and differentiation. Here we report that adult MSCs express functional Toll-like receptors (TLRs), confirmed by the responses of MSCs 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 the 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, MSCs derived from myeloid factor 88 (MyD88)–deficient mice lacked the capacity to differentiate effectively into osteogenic and chondrogenic cells. It appears that TLRs 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: C. Bouffi, F. Djouad, M. Mathieu, D. Noel, and C. Jorgensen Multipotent mesenchymal stromal cells and rheumatoid arthritis: risk or benefit? Rheumatology, June 26, 2009; (2009) kep162v1. [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. 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