Immune plasticity of bone marrow-derived mesenchymal stromal cells

Isolated from simple bone marrow aspirates, mesenchymal stromal cells (MSCs) can be easily expanded ex vivo and differentiated into various cell lineages. Because they are present in humans of all ages, are harvested in the absence of prior mobilization and preserve their plasticity following gene modification, MSCs are particularly attractive for cell-based medicine. One of the most fascinating properties of ex vivo expanded MSCs is their ability to suppress ongoing immune responses, both in vitro and in vivo. Although not fully understood, the immunosuppressive properties of MSCs have been reported to affect the function of a broad range of immune cells, including T cells, antigen-presenting cells, natural killer cells and B cells. Whereas successful harnessing of these immunosuppressive properties might one day open the door to the development of new cell-based strategies for the control of graft-versus-host and other autoimmune diseases, recent studies suggest that the immune-modulating properties of MSCs are far more complex than first thought. Reminiscent of the dichotomy of function of dendritic cells (DCs), which can act as potent activators or potent suppressors of immune responses, new studies including our own work has shown that MSCs in fact possess the dual ability to suppress or activate immune responses. In this review, we summarize the different biological properties of MSCs and discuss the current literature on the complex mechanism of immune modulation mediated by ex vivo expanded MSCs.