Exosomes derived from cord blood Treg cells promote diabetic wound healing by targeting monocytes.

Autor: Yang F; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China., Cai D; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China., Kong R; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China., Bi Y; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China., Zhang Y; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China., Lei Y; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China., Peng Y; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China., Li X; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China., Xiao Y; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China., Zhou Z; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China., Yu H; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China. Electronic address: yuhaibo616@csu.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Aug; Vol. 226, pp. 116413. Date of Electronic Publication: 2024 Jul 05.
DOI: 10.1016/j.bcp.2024.116413
Abstrakt: Chronic nonhealing diabetic wounds are a critical clinical challenge. Regulatory T cells (Tregs) are immunosuppressive modulators affecting wound healing progression by controlling the inflammatory response. The current study attempted to investigate whether the exosomes derived from cord blood (CB) Tregs can accelerate the healing process. Exosomes were isolated from CB-Treg cultures using ultracentrifugation and validated with different specific markers of exosomes. The purified CB-Treg-derived exosomes were co-cultured with peripheral blood mononuclear cells (PBMCs) and CD14 + monocytes. The migration-promoting effect of CB-Treg-derived exosomes on fibroblasts and endothelial cells was investigated. We used thermosensitive Pluronic F-127 hydrogel (PF-127) loaded with CB-Treg-derived exosomes in a diabetic wound healing mouse model. CB-Treg-derived exosomes with 30-120 nm diameters revealed exosome-specific markers, such as TSG101, Alix, and CD63. CB-Treg-derived exosomes were mainly bound to the monocytes when co-cultured with PBMCs, and promoted monocyte polarization to the anti-inflammatory phenotype (M2) in vitro. CB-Treg-derived exosomes enhanced the migration of endothelial cells and fibroblasts. Furthermore, CB-Treg-derived exosomes treatment accelerated wound healing by downregulating inflammatory factor levels and upregulating the M2 macrophage ratio in vivo. Our findings indicated that CB-Treg-derived exosomes could be a promising cell-free therapeutic strategy for diabetic wound healing, partly by targeting monocytes.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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