Toll-like Receptor–Mediated Signaling in Human Adipose-Derived Stem Cells: Implications for Immunogenicity and Immunosuppressive Potential

Human adipose-derived stem cells (hASCs) are mesenchymal stem cells with reduced immunogenicity and the capability to modulate immune responses. These properties make hASCs of special interest as therapeutic agents in the settings of chronic inflammatory and autoimmune diseases. Exogenous and endogenous toll-like receptor (TLR) ligands have been linked with the perpetuation of inflammation in a number of chronic inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis because of the permanent exposure of the immune system to TLR-specific stimuli. Therefore, hASCs employed in therapy are potentially exposed to TLR ligands, which may result in the modulation of hASC activity and therapeutic potency. In this study, we demonstrate that hASCs possess active TLR2, TLR3, and TLR4, because activation with specific ligands resulted in induction of nuclear factor kappa B–dependent genes, such as manganese superoxide dismutase and the release of interleukin (IL)-6 and IL-8. TLR3 and TLR4 lig...