MSCs and Innate Immune Responses: A Balancing Act

Abstract

The immunoregulatory functions of bone marrow-derived stromal cells (BMSCs), also called mesenchymal stromal/stem cells (MSCs), have been studied extensively in recent years. Although there is still some confusion in the literature about the nomenclature, for the sake of simplicity, we will use the abbreviation MSC below, referring to cells isolated by their adherence to plastic, which might be derived from a variety of tissues (and might not have identical features). Most investigators who examined the mechanisms responsible for the immunomodulatory actions of MSCs focused on the interactions between the latter and cells that comprise the adaptive immune system (T and B cells). Recently, however, an increasing number of publications have described interactions between MSCs and neutrophil granulocytes and have provided data suggesting that effects on monocytes and macrophages may play a major role in MSC-induced immunomodulation. For example, MSCs were shown to enhance the antibacterial activities of neutrophil granulocytes preventing organ injury caused by the uncontrolled activation of these cells. Furthermore, MSCs were reported to modulate the functions of the monocyte/macrophage lineage by inducing these cells to acquire an anti-inflammatory phenotype. This phenotypic switch seems to be critical not only in the prevention of sepsis-induced multiorgan failure but also in the protection by MSCs seen in autoimmune settings. In fact, data suggest that MSC-macrophage interactions may even be a key intermediate step in the MSC-mediated protection from T cell-driven autoimmunity. In this chapter, we summarize the most important findings that led to these conclusions.