Related Experiment Video
Updated: Jul 12, 2025
Prospective, Randomized, and Controlled Study of a Human Umbilical Cord Mesenchymal Stem Cell Injection for Treating Diabetic Foot Ulcers
Published on: March 3, 2023
The bone mesenchymal stem cell-derived exosomal miR-146a-5p promotes diabetic wound healing in mice via macrophage
Xijie Zhou1, Chenhao Ye1, Liangfu Jiang1
1Department of Hand and Microsurgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Abstract:
A diabetic wound is a refractory disease that afflicts patients globally. MicroRNA-146a-5p (miR-146a-5p) is reported to represent a potential therapeutic target for diabetic wounds. However, microRNA easily degrades in the wound microenvironment. This study extracted bone marrow mesenchymal stem cell (BMSC)-derived exosomes (EXO). Electroporation technology was used to load miR-146a-5p into EXO (labeled as EXO-miR-146a). The endothelial cells (human umbilical vein endothelial cells [HUVECs]) and macrophages were cocultured in transwell chambers in the presence of high glucose. Cell proliferation, migration, and angiogenesis were measured with cell counting kit 8, scratch, and tube forming assays, respectively. Flow cytometry was introduced to validate the biomarker of macrophages and BMSCs. The expression level of macrophage polarization-related proteins and tumor necrosis factor receptor-associated factor 6 (TRAF6) was assessed with western blotting analysis. The full-thickness skin wound model was developed to verify the in vitro results. EXO-miR-146a promoted the proliferation, migration, and angiogenesis of HUVECs in the hyperglycemic state by suppressing the TRAF6 expression in vitro. Additionally, EXO-miR-146a treatment facilitated M2 but inhibited M1 macrophage polarization. Furthermore, EXO-miR-146a enhances reepithelialization, angiogenesis, and M2 macrophage polarization, thereby accelerating diabetic wound healing in vivo. The EXO-miR-146a facilitated M2 macrophage polarization, proliferation, migration, and angiogenesis of HUVECs through TRAF6, thereby ameliorating intractable diabetic wound healing. These results established the basis for using EXO to deliver drugs and revealed mediators for diabetic wound treatment.
Insights
Exosomes loaded with microRNA-146a-5p (EXO-miR-146a) accelerate diabetic wound healing. This therapy promotes blood vessel formation and shifts immune cells to an anti-inflammatory state, offering a new treatment for chronic wounds.
Area of Science:
- Regenerative Medicine
- Biotechnology
- Wound Healing Research
Background:
- Diabetic wounds are difficult to treat globally.
- MicroRNA-146a-5p (miR-146a-5p) shows therapeutic potential but degrades easily.
- Bone marrow mesenchymal stem cell (BMSC)-derived exosomes (EXO) can protect microRNAs.
Purpose of the Study:
- To investigate the efficacy of EXO loaded with miR-146a-5p (EXO-miR-146a) for diabetic wound healing.
- To explore the underlying mechanisms involving endothelial cells and macrophage polarization.
Main Methods:
- EXO were engineered to carry miR-146a-5p via electroporation.
- In vitro studies used co-cultured human umbilical vein endothelial cells (HUVECs) and macrophages under high glucose conditions.
- In vivo studies utilized a full-thickness skin wound model in diabetic mice.
Main Results:
- EXO-miR-146a significantly promoted HUVEC proliferation, migration, and angiogenesis in vitro by suppressing TRAF6 expression.
- EXO-miR-146a treatment induced M2 macrophage polarization while inhibiting M1 polarization.
- In vivo, EXO-miR-146a accelerated wound reepithelialization, angiogenesis, and M2 polarization, leading to improved diabetic wound healing.
Conclusions:
- EXO-miR-146a effectively promotes diabetic wound healing by enhancing endothelial function and M2 macrophage polarization via TRAF6.
- Engineered exosomes represent a promising drug delivery system for treating intractable diabetic wounds.
