Impaired wound healing presents great health risks to patients. While encouraging, the current clinical successes of mesenchymal stromal cell (MSC)-based therapies for tissue repair have been limited. Genetic engineering could endow MSCs with more robust regenerative capacities. Here, we identified that C-C motif chemokine receptor 2 (CCR2) overexpression enhanced the targeted migration and immunoregulatory potential of MSCs in response to C-C motif chemokine ligand 2 (CCL2) in vitro. Intravenously infusion of CCR2-engineered MSCs (MSCsCCR2) exhibited improved homing efficiencies to injured sites and lungs of diabetic mice. Accordingly, MSCCCR2 infusion inhibited monocyte infiltration, reshaped macrophage inflammatory properties, prompted the accumulation of regulatory T cells (Treg cells) in injured sites, and reshaped systemic immune responses via the lung and spleen in mouse diabetic wound models. In summary, CCR2-engineered MSCs restore immunological homeostasis to accelerate diabetic wound healing via their improved homing and immunoregulatory potentials in response to CCL2. Therefore, these findings provide a novel strategy to explore genetically engineered MSCs as tools to facilitate tissue repair in diabetic wounds.
Keywords: CCR2; Diabetes mellitus; Immunoregulation; MSC homing; Tissue repair.
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