Extracellular vesicle-derived lncRNA VIM-AS1 promotes diabetic wound healing by promoting glycolysis and alleviating cellular senescence.

IF 7.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Research & Therapy Pub Date : 2025-07-01 DOI:10.1186/s13287-025-04451-x

Feiyuan Liang, Nanchang Huang, Yu Tian, Yuqi Fang, Chuangming Huang, Boyuan Qiu, Tiantian Lu, Li Zheng, Jianwen Cheng, Bo Zhu, Jinmin Zhao

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Abstract

Aims: Diabetic wound healing is a significant challenge due to impaired cellular functions, and current therapeutic approaches often prove inadequate. This study aims to explore the role of extracellular vesicles (EVs) derived from human umbilical mesenchymal stem cells (HuMSCs), particularly focusing on their associated long non-coding RNAs (lncRNAs), in promoting diabetic wound repair.

Methods: To investigate this, we employed lncRNA sequencing of EVs, created reprogrammed EVs, and utilized a diabetic rat model. The impact of HuMSCs-derived EVs on fibroblast glycolysis, proliferation, and migration was assessed, along with the function of lncRNA VIM-AS1 in glucose metabolism via the PPAR-γ pathway.

Results: Our results demonstrate that HuMSCs-derived EVs enhance glycolysis in fibroblasts, which is essential for effective wound healing. We identified lncRNA VIM-AS1 as a pivotal regulator that not only promotes fibroblast proliferation and migration but also significantly enhances endothelial cell function, specifically regarding angiogenesis and tissue vascularization. Furthermore, EVs-derived lncRNA VIM-AS1 was found to reduce reactive oxygen species (ROS) levels, thereby mitigating oxidative stress and cellular senescence in both fibroblasts and endothelial cells. In vivo experiments in rat models confirmed the capacity of EVs-derived lncRNA VIM-AS1 to improve diabetic wound healing.

Conclusions: This study highlights the therapeutic potential of HuMSCs-derived EVs and specifically lncRNA VIM-AS1 as innovative approaches to address the challenges of tissue repair in diabetic conditions, offering promising strategies for enhancing wound healing efficacy.

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细胞外囊泡来源的lncRNA VIM-AS1通过促进糖酵解和减轻细胞衰老来促进糖尿病伤口愈合。

目的：由于细胞功能受损，糖尿病伤口愈合是一个重大挑战，目前的治疗方法往往被证明是不够的。本研究旨在探讨来自人脐带间充质干细胞（HuMSCs）的细胞外囊泡（EVs）在促进糖尿病伤口修复中的作用，特别是关注其相关的长链非编码rna （lncRNAs）。方法：为了研究这一点，我们对ev进行了lncRNA测序，创建了重编程ev，并利用糖尿病大鼠模型。我们评估了humscs衍生的ev对成纤维细胞糖酵解、增殖和迁移的影响，以及lncRNA VIM-AS1通过PPAR-γ途径在葡萄糖代谢中的功能。结果：我们的研究结果表明，humscs衍生的ev增强了成纤维细胞的糖酵解，这对有效的伤口愈合至关重要。我们发现lncRNA VIM-AS1是一个关键调节因子，不仅促进成纤维细胞增殖和迁移，而且显著增强内皮细胞功能，特别是在血管生成和组织血管化方面。此外，研究发现ev衍生的lncRNA VIM-AS1可降低活性氧（ROS）水平，从而减轻成纤维细胞和内皮细胞的氧化应激和细胞衰老。在大鼠模型中的体内实验证实了ev衍生的lncRNA VIM-AS1促进糖尿病伤口愈合的能力。结论：本研究强调了humscs衍生的ev的治疗潜力，特别是lncRNA VIM-AS1作为解决糖尿病患者组织修复挑战的创新方法，为提高伤口愈合效果提供了有希望的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

13.20

自引率

8.00%

发文量

525

审稿时长

1 months

期刊介绍： Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.