Mechanisms of mesenchymal stromal cell immunomodulation

Multipotent mesenchymal stromal cells (MSCs) have generated considerable interest in the fields of regenerative medicine, cell therapy and immune modulation. Over the past 5 years, the initial observations that MSCs could enhance regeneration and modulate immune responses have been significantly advanced and we now have a clearer picture of the effects that MSCs have on the immune system particularly in the context of inflammatory‐mediated disorders. A number of mechanisms of action have been reported in MSC immunomodulation, which encompass the secretion of soluble factors, induction of anergy, apoptosis, regulatory T cells and tolerogenic dendritic cells. It is clear that MSCs modulate both innate and adaptive responses and evidence is now emerging that the local microenvironment is key in the activation or licensing of MSCs to become immunosuppressive. More recently, studies have suggested that MSCs have the capacity to sense their environment and have a role in pathogen clearance in conjunction with the resolution of insult or injury. This review focuses on the mechanisms of MSC immunomodulation discussing the multistep process of MSC localisation at sites of inflammation, the cross talk between MSCs and the local microenvironment as well as the subsequent mechanisms of action used to resolve inflammation. The January 2013 issue contains a Special Feature Focussing on the interface between mesenchymal stromal cells and the immune system. Mesenchymal stromal cells (MSCs) are known to play a fundamental role in supporting hematopoiesis and are multipotent. This knowledge has led to significant interest to determine the potential of using MSCs both to enhance hematopoietic recovery following bone marrow transplantation and also for regenerative medical purposes. Further studies showed that MSCs also had immunosuppressive activity on both the adaptive and natural immune system, thereby endorsing them as the perfect cell source for tissue repair. The Special Feature contains review articles covering topics that largely focus on the interactions of MSCs with cells of the immune system. Further background information on this important topic is available through the accompanying web focus which links to related articles from across Nature Publishing Group.