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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.
 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.
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