Fig. 1.

MSCs and macrophages reciprocally influence each other. Naïve MSCs secrete basal levels of anti-inflammatory cytokines [13, 88]. Inflammatory macrophages secrete numerous molecules that act as inflammatory stimuli modulating a shift from naïve MSC to “activated” MSC (“inflammatory activation”). The activated MSCs have switched on their immunomodulatory program, which results in the secretion of similar molecules as naïve MSCs but in greater levels. These high levels of anti-inflammatory cytokines drive the switch from inflammatory to anti-inflammatory macrophages (“immunosuppression”), which are important in tissue repair and remodeling. The specific stimuli and molecular hierarchy involved in these cells regulation is still incompletely characterized [11, 23, 27, 92, 94–98]