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<p>Chronic trauma is a prevalent and significant complication of diabetes. Mesenchymal stem cell(MSC)-derived exosomes (Exos) have been reported to accelerate the healing of chronic diabetic wounds. MSCs pretreated with chemical or biological factors were reported to enhance the biological activity of MSC-derived exosomes. Hence, this study investigated the role of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) pretreated with metformin (MET) on diabetic wound healing. The results showed that MET-Exos promoted endothelial cell migration, tube formation, and angiogenesis, leading to accelerated wound healing in diabetic mice. Mechanistically, MET-Exos upregulated LINC-PINT, which, through competitive binding to miR-139-3p, activated FOXC2, a key regulator of angiogenesis. These data reveal that MET-Exos might promote revascularization and wound healing through the LINC-PINT/miR-139-3p/FOXC2 axis, showing its potential as a therapeutic modality for diabetic wounds.</p> Graphical Abstract <p></p>

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Exosomes Derived from Metformin-Pretreated BMSCs Accelerate Diabetic Wound Repair by Promoting Angiogenesis Via the LINC-PINT/miR-139-3p/FOXC2 Axis

  • 期刊论文

  • 发表日期：

    2025年3月20日

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  • Xiaobao Gu,
  • Teng Li,
  • Xiangyang Yin,
  • Pengbo Zhai,
  • Deyu Jiang,
  • Ding Sun,
  • Hongxu Yan,
  • Bing Wang

摘要

Chronic trauma is a prevalent and significant complication of diabetes. Mesenchymal stem cell(MSC)-derived exosomes (Exos) have been reported to accelerate the healing of chronic diabetic wounds. MSCs pretreated with chemical or biological factors were reported to enhance the biological activity of MSC-derived exosomes. Hence, this study investigated the role of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) pretreated with metformin (MET) on diabetic wound healing. The results showed that MET-Exos promoted endothelial cell migration, tube formation, and angiogenesis, leading to accelerated wound healing in diabetic mice. Mechanistically, MET-Exos upregulated LINC-PINT, which, through competitive binding to miR-139-3p, activated FOXC2, a key regulator of angiogenesis. These data reveal that MET-Exos might promote revascularization and wound healing through the LINC-PINT/miR-139-3p/FOXC2 axis, showing its potential as a therapeutic modality for diabetic wounds.

Graphical Abstract