CCR2-engineered mesenchymal stromal cells accelerate diabetic wound healing by restoring immunological homeostasis. (August 2021)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Biomaterials. Volume 275(2021)
• Publication Date: 2021-08
• Subjects: Diabetes mellitus -- CCR2 -- Tissue repair -- Immunoregulation -- MSC homing; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2021.120963
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: 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 (MSCs CCR2 ) exhibited improved homing efficiencies to injured sites and lungs of diabetic mice. Accordingly, MSC CCR2 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.