Hypoxic adipose-derived stem cell exosomes as carriers of miR-100-5p to enhance angiogenesis and suppress inflammation in diabetic foot ulcers

IF 3.6 3区生物学 Q3 CELL BIOLOGY

Journal of Cell Communication and Signaling Pub Date : 2025-06-27 DOI:10.1002/ccs3.70018

Hong Liu, Fei Hao, Bangtao Chen

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引用次数: 0

Abstract

Diabetic foot ulcer (DFU) is a severe diabetes complication characterized by impaired angiogenesis and chronic inflammation, leading to delayed wound healing. Exosomes (Exo) derived from hypoxic adipose-derived stem cells (H-ADSCs-Exo) show potential as therapeutic carriers. This study investigates the role of H-ADSCs-Exo carrying miR-100-5p in DFU healing. ADSCs were isolated, characterized, and their Exo analyzed via transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Transcriptome sequencing identified miR-100-5p as a key modulator of angiogenesis and inflammation. In vitro, H-ADSCs-Exo enhanced human umbilical vein endothelial cell and fibroblast proliferation, migration, and tube formation. In a rat DFU model, H-ADSCs-Exo administration reduced ulcer size, increased angiogenesis (VEGF/CD31 expression), and decreased inflammatory markers (TNF-α, IL-6). miR-100-5p overexpression further amplified these effects, demonstrating its critical role in Exo-mediated healing. These findings highlight the therapeutic potential of H-ADSCs-Exo in DFU treatment, offering insights into cell signaling mechanisms and paving the way for miRNA-based regenerative therapies.

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低氧脂肪来源的干细胞外泌体作为miR-100-5p的载体，在糖尿病足溃疡中促进血管生成和抑制炎症

糖尿病足溃疡（DFU）是一种严重的糖尿病并发症，其特征是血管生成受损和慢性炎症，导致伤口愈合延迟。来自缺氧脂肪来源干细胞（H-ADSCs-Exo）的外泌体（Exo）显示出作为治疗载体的潜力。本研究探讨了携带miR-100-5p的H-ADSCs-Exo在DFU愈合中的作用。分离ADSCs，对其进行表征，并通过透射电子显微镜、纳米颗粒跟踪分析和Western blot分析其Exo。转录组测序鉴定miR-100-5p是血管生成和炎症的关键调节剂。在体外，H-ADSCs-Exo增强人脐静脉内皮细胞和成纤维细胞的增殖、迁移和管的形成。在大鼠DFU模型中，H-ADSCs-Exo可减小溃疡大小，增加血管生成（VEGF/CD31表达），降低炎症标志物（TNF-α, IL-6）。miR-100-5p过表达进一步放大了这些作用，证明了其在exo介导的愈合中的关键作用。这些发现突出了H-ADSCs-Exo在DFU治疗中的治疗潜力，提供了对细胞信号传导机制的见解，并为基于mirna的再生治疗铺平了道路。

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来源期刊

Journal of Cell Communication and Signaling CELL BIOLOGY-

CiteScore

6.40

自引率

4.90%

发文量

期刊介绍： The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.