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

The MSC and macrophage dyad theorem. MSCs polarize macrophages to an 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 injury syndromes. AbstractPharmacological depletion of macrophagesin 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 IL‐10 suppressive efferocytotic response. In addi tion, 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 functional convergence , implantation of CCL2+ MSCs in the extravascular space where interaction with lung resident perivascular macrophages is not operative, also leads to IL ‐10 polarization of CCR2+ mac...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Regenerative Medicine Source Type: research