Mesenchymal stromal progenitor 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. We found that adult mouse 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, induced nuclear factor kB (NF-kB) translocation, reduced basal motility and increased MSC proliferation. The hallmark of MSC function is their capacity to differentiate into several mesodermal lineages. Pam3Cys inhibited MSC differentiation into osteogenic, adipogenic and chondrogenic cells while sparing their immunosuppressive effect. Moreover, MSC derived from myeloid factor 88 (MyD88) deficient mice, that are unable to properly respond to most TLR ligands, lacked the capacity to differentiate effectively into osteogenic and chondrogenic cells. In addition, we find that human bone marrow-derived MSC express TLR-1 through TLR-10. At least some of these receptors are functional: Some TLR ligands induce cytokine secretion and affect MSC proliferation and differentiation. It appears that TLR and their ligands can serve as regulators of MSC proliferation and differentiation and might affect the maintenance of MSC renewal and multipotency.
