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

IF 4.2 3区医学 Q2 CELL & TISSUE ENGINEERING Stem Cell Reviews and Reports Pub Date : 2025-05-01 Epub Date: 2025-03-20 DOI:10.1007/s12015-025-10860-5

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

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Abstract

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.

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二甲双胍预处理的骨髓间质干细胞外泌体通过LINC-PINT/miR-139-3p/FOXC2轴促进血管生成，从而加速糖尿病伤口修复。

慢性创伤是糖尿病的一种普遍而重要的并发症。据报道，间充质干细胞（MSC）衍生的外泌体（Exos）可以加速慢性糖尿病伤口的愈合。据报道，用化学或生物因子预处理的间充质干细胞可以增强间充质干细胞衍生的外泌体的生物活性。因此，本研究探讨了二甲双胍（MET）预处理的骨髓间充质干细胞（BMSCs）衍生的外泌体在糖尿病伤口愈合中的作用。结果表明，MET-Exos促进了内皮细胞的迁移、管的形成和血管生成，从而加速了糖尿病小鼠的伤口愈合。在机制上，MET-Exos上调了LINC-PINT，其通过与miR-139-3p的竞争性结合，激活了FOXC2，这是血管生成的关键调节因子。这些数据表明MET-Exos可能通过LINC-PINT/miR-139-3p/FOXC2轴促进血运重建和伤口愈合，显示其作为糖尿病伤口治疗方式的潜力。

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索莱宝

phalloidin

索莱宝

PKH26

索莱宝

metformin

来源期刊

Stem Cell Reviews and Reports 医学-细胞生物学

CiteScore

9.30

自引率

4.20%

发文量

审稿时长

3 months

期刊介绍： The purpose of Stem Cell Reviews and Reports is to cover contemporary and emerging areas in stem cell research and regenerative medicine. The journal will consider for publication: i) solicited or unsolicited reviews of topical areas of stem cell biology that highlight, critique and synthesize recent important findings in the field. ii) full length and short reports presenting original experimental work. iii) translational stem cell studies describing results of clinical trials using stem cells as therapeutics. iv) papers focused on diseases of stem cells. v) hypothesis and commentary articles as opinion-based pieces in which authors can propose a new theory, interpretation of a controversial area in stem cell biology, or a stem cell biology question or paradigm. These articles contain more speculation than reviews, but they should be based on solid rationale. vi) protocols as peer-reviewed procedures that provide step-by-step descriptions, outlined in sufficient detail, so that both experts and novices can apply them to their own research. vii) letters to the editor and correspondence. In order to facilitate this exchange of scientific information and exciting novel ideas, the journal has created five thematic sections, focusing on: i) the role of adult stem cells in tissue regeneration; ii) progress in research on induced pluripotent stem cells, embryonic stem cells and mechanism governing embryogenesis and tissue development; iii) the role of microenvironment and extracellular microvesicles in directing the fate of stem cells; iv) mechanisms of stem cell trafficking, stem cell mobilization and homing with special emphasis on hematopoiesis; v) the role of stem cells in aging processes and cancerogenesis.