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Cell Reports Medicine

Cell Reports Medicine

IF: 11.7
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Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients

Published:18 June 2024 DOI: 10.1016/j.xcrm.2024.101588 PMID: 38781961
Jing Xie,?Xuhua Liu,?Biaoliang Wu,?Bochong Chen,?Qiancheng Song,?Yuan Guan,?Yuanxun Gong,?Chengliang Yang,?Jinbo Lin,?Mingfeng Huang,?Xinyu Tan,?Ruijun Lai,?Xiaozhen Lin,?Sheng Zhang,?Xiaoling Xie,?Xiaoli Chen,?Chunyuan Zhang,?Mei Yang,?Huijiao Nong,?Xiaoyang Zhao,?Laixin Xia,?Weijie Zhou,?Guozhi Xiao,?Qing Jiang,?Weiguo Zou,?Di Chen,?Di Lu,?Jia Liu,?Xiaochun Bai

Abstract

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.

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