Immune regulation by mesenchymal stem cells: two sides to the coin

Mesenchymal stem cells (MSCs) constitute a rare population of adult stem cells that can be isolated from a simple bone marrow aspirate in the absence of prior mobilization. For this reason, MSCs are particularly attractive for cell-based medicine. Ex-vivo-expanded MSCs isolated from different species, including human MSCs, have been shown to suppress the activity of a broad range of immune cells, including T cells, antigen-presenting cells, natural killer (NK) cells and B cells. New studies have further shown that MSCs interact with NK cells, express NK cell receptor ligands, express Toll-like receptors (TLRs), respond to TLR ligands and act as antigen-presenting cells upon interferon-gamma stimulation. Taken together, these studies suggest that MSCs may constitute a previously unrecognized player of the immune system with dichotomy of function reminiscent of other antigen-presenting cells. An important question that remains unanswered is whether resident MSCs actually play a role in endogenous immune responses? I here review the mechanisms of MSC-mediated immune regulation and discuss the major roles of resident MSCs in health and disease.