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

Cell Rep Med

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; 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. Electronic address:

Published: June 2024

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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228591PMC
http://dx.doi.org/10.1016/j.xcrm.2024.101588DOI Listing

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