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Journal Article Epublish

PubMed: 40597411 DOI: 10.1186/s13287-025-04451-x

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

Stem Cell Res Ther 16(1):341

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

Affiliations

  • Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Medical University, Nanning, 530021, China. Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
  • Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Medical University, Nanning, 530021, China.
  • Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. The BioMolecular Omics Teaching and Research Section, Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China.
  • Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Medical University, Nanning, 530021, China. The BioMolecular Omics Teaching and Research Section, Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China.
  • Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Medical University, Nanning, 530021, China. Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
  • Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Medical University, Nanning, 530021, China. The BioMolecular Omics Teaching and Research Section, Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China.
  • Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Medical University, Nanning, 530021, China. Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. The BioMolecular Omics Teaching and Research Section, Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China. Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.

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.

MeSH

Cells, Extracellular Vesicles, Cellular Senescence, Stem Cells, Endothelial Cells, Fibroblasts, Therapeutics, Tissues, Rna, Long Noncoding