Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients

Jing Xie1,2; Xuhua Liu1,4; Biaoliang Wu2,3; Bochong Chen1; Qiancheng Song1; Yuan Guan2,3; Yuanxun Gong2,3; Chengliang Yang2,3; Jinbo Lin1; Mingfeng Huang1; Xinyu Tan1,4; Ruijun Lai1,4; Xiaozhen Lin2,3; Sheng Zhang1; Xiaoling Xie1; Xiaoli Chen1; Chunyuan Zhang2,3; Mei Yang2,3; Huijiao Nong2,3; Xiaoyang Zhao5; Laixin Xia5; Weijie Zhou6; Guozhi Xiao7; Qing Jiang8; Weiguo Zou9; Di Chen10; Di Lu11; Jia Liu2,3; Xiaochun Bai1,4

2024-06-18

10.1016/j.xcrm.2024.101588

Cell Reports Medicine   影响因子和分区

2666-3791

Tibial cortex transverse distraction is a surgical method for treating severe diabetic foot ulcers (DFUs), but the underlying mechanism is unclear. We show that antioxidant proteins and small extracellular vesicles (sEVs) with multiple-tissue regenerative potential are released during bone transport (BT) in humans and rats. These vesicles accumulate in diabetic wounds and are enriched with microRNAs (miRNAs) (e.g., miR-494-3p) that have high regenerative activities that improve the circulation of ischemic lower limbs while also promoting neovascularization, fibroblast migration, and nerve fiber regeneration. Deletion of miR-494-3p in rats reduces the beneficial effects of BT on diabetic wounds, while hydrogels containing miR-494-3p and reduced glutathione (GSH) effectively repair them. Importantly, the ginsenoside Rg1 can upregulate miR-494-3p, and a randomized controlled trial verifies that the regimen of oral Rg1 and GSH accelerates wound healing in refractory DFU patients. These findings identify potential functional factors for tissue regeneration and suggest a potential therapy for DFUs.

bone transport diabetic wound healing ginsenoside small extracellular vesicles tissue regeneration

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其他

2-s2.0-85195418338

人工提交

1.Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
2.Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
3.Guangxi Health Commission Key Laboratory of Biomedical Materials Research, Guangxi Health Commission Key Laboratory of Clinical Medicine Research on Bone and Joint Degenerative Diseases Cohort, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Baise 533000, China
4.Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China
5.Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
6.Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
7.Department of Biochemistry, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen 518055, China
8.State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
9.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
10.Research Center for Human Tissue and Organ Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
11.Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, China

Jing Xie,Xuhua Liu,Biaoliang Wu,et al. Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients[J]. Cell Reports Medicine,2024,5(6).

Jing Xie.,Xuhua Liu.,Biaoliang Wu.,Bochong Chen.,Qiancheng Song.,...&Xiaochun Bai.(2024).Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients.Cell Reports Medicine,5(6).

Jing Xie,et al."Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients".Cell Reports Medicine 5.6(2024).