Macrophages at the nexus of mesenchymal stromal cell potency: The emerging role of chemokine cooperativity

The mesenchymal stromal cell (MSC) and macrophage dyad theorem. MSCs polarize macrophages to an interleukin (IL) ‐10 anti‐inflammatory and regenerative functionality via secretome containing heteroplexed chemokines (and other active factors) or efferocytosis. Both macrophage IL‐10 licensing pathways—MSC function dependent and independent—converge to affect clinical outcomes in inflammatory tissue inj ury syndromes. AbstractPharmacological depletion of macrophages in vivo with liposomal clodronate renders mice unresponsive to adoptive transfer of mesenchymal stromal cells (MSCs) for affecting outcomes of acute inflammatory pathology. This experimental observation identifies host macrophages as necessary in mediating the salutary anti ‐inflammatory properties of MSCs as a cellular pharmaceutical. This theory is supported by the observation that transfusion of MSCs leads to the prompt phagocytosis of nearly half of lung entrapped MSCs by lung resident macrophages, triggering an interleukin (IL)‐10 suppressive efferocytotic res ponse. In addition, non‐phagocytosed MSCs with COX2 competency shape the immune milieu by inducing tissue macrophages to express IL‐10. Additional experimental evidence identifies MSC‐borne IL‐6, IDO and TSG‐6 as directly involved in macrophage polarization. Along similar lines of function al convergence, implantation of CCL2+ MSCs in the extravascular space where interaction with lung resident perivascular macrophages is not operat...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Concise Review Source Type: research