CCR2-engineered mesenchymal stromal cells accelerate diabetic wound healing by restoring immunological homeostasis

作者：Kuang, Shuhong; He, Feng; Liu, Guihua; Sun, Xiangzhou; Dai, Jian; Chi, Ani; Tang, Yali; Li, Zhuoran; Gao, Yong; Deng, Chunhua; Lin, Zhengmei^*; Xiao, Haipeng^*; Zhang, Min^*

来源：Biomaterials, 2021, 275: 120963.

DOI：10.1016/j.biomaterials.2021.120963

• Diabetes mellitus
• CCR2
• Tissue repair
• Immunoregulation
• MSC homing

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.

• 单位
  6; 1; 中山大学