title: Toll-like receptors and their ligands control mesenchymal stem cell functions.
abstract: 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 kappa B (NF-kappaB) 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.
authors.affiliation: Department of Molecular Cell Biology, the Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Meirav
authors.initials: M
authors.lastname: Pevsner-Fischer
authors.forename: Vered
authors.initials: V
authors.lastname: Morad
authors.forename: Michal
authors.initials: M
authors.lastname: Cohen-Sfady
authors.forename: Liat
authors.initials: L
authors.lastname: Rousso-Noori
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zanin-Zhorov
authors.forename: Shmuel
authors.initials: S
authors.lastname: Cohen
authors.forename: Irun R
authors.initials: IR
authors.lastname: Cohen
authors.forename: Dov
authors.initials: D
authors.lastname: Zipori
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D020219:Chondrogenesis; D008024:Ligands; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis; D051193:Toll-Like Receptors / Q000502:physiology*
chemical_list: D008024:Ligands; D051193:Toll-Like Receptors