Evidence map›Paper›PMID 40518546›Full record

ArticleStem cell research & therapy2025

Adipose-derived stem cells extracellular vesicles enhance diabetic wound healing via CCN2/PI3K/AKT pathway: therapeutic potential and mechanistic insights.

Yu-Lu Zhou, Shingo Ogura, Hao Ma, Rong-Bin Liang, Shao-Yihan Fang, Yue-Ming Wang, Yan Wo, Wen-Jin Wang, De-Wu Liu

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Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Yu-Lu Zhou *Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Shingo Ogura *Department of Anatomy and Physiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Hao Ma *Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Rong-Bin LiangDepartment of Ophthalmology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Shao-Yihan FangMedical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Yue-Ming WangDepartment of Anatomy and Physiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Yan WoDepartment of Anatomy and Physiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. woyansh@163.com.
Wen-Jin WangDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wangwenjin_001@163.com.
De-Wu LiuMedical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. ndyfy00706@ncu.edu.cn.

Funding

National Natural Science Foundation of China 81460293National Natural Science Foundation of China 82102357National Natural Science Foundation of China 82460447Shanghai Key Research and Development Center - Shanghai Research Center of Plastic and Reconstructive Surgery 2023ZZ02023
6 · The paper itself

Abstract

backgroundAdipose-derived stem cells extracellular vesicles (ADSCs-EVs) hold significant promise in tissue repair and regeneration. While they have been reported to enhance diabetic wound healing, the precise mechanisms remain unclear.

methodsADSCs-EVs were isolated via ultracentrifugation and characterized through transmission electron microscopy, Western blot, and nanoparticle tracking analysis. Their effects on human umbilical vein endothelial cells (HUVECs) and RAW 264.7 macrophages were assessed in vitro, focusing on cell proliferation, migration, tube formation, and macrophage polarization. A diabetic rat wound model was used to evaluate their therapeutic impact on wound healing and angiogenesis, with histological and immunofluorescence analyses. mRNA sequencing identified Cellular communication network factor 2(CCN2) as a key upregulated gene, leading to further exploration of its role in ADSCs-EVs-mediated angiogenesis and wound healing via the PI3K/AKT pathway. Gene silencing (si-CCN2) and pharmacological inhibition (LY294002) were employed both in vitro and in vivo.

resultsADSCs-EVs were successfully isolated and characterized. In vitro, ADSCs-EVs promoted HUVEC proliferation, migration, and tube formation, and facilitated macrophage polarization to the M2 phenotype. In vivo studies using a diabetic rat wound model confirmed the pro-healing effects of ADSCs-EVs, including enhanced angiogenesis, granulation tissue formation, and accelerated wound closure. mRNA sequencing revealed that CCN2 expression was significantly upregulated in diabetic wound tissues treated with ADSCs-EVs. Further experiments showed that inhibiting CCN2 expression (si-CCN2) or blocking the PI3K/AKT pathway (LY294002) partially suppressed HUVEC proliferation, migration, tube formation, and angiogenesis, and counteracted the pro-healing effects of ADSCs-EVs.

conclusionsADSCs-EVs promote diabetic wound healing through the CCN2/PI3K/AKT pathway, offering a promising therapeutic target for diabetic wound repair.

Indexed as

Adipose TissueConnective Tissue Growth FactorDiabetes Mellitus, ExperimentalExtracellular VesiclesStem CellsWound HealingAnimalsCell MovementCell ProliferationHumansHuman Umbilical Vein Endothelial CellsMacrophagesMaleMiceNeovascularization, PhysiologicPhosphatidylinositol 3-KinasesCCN2 protein, humanConnective Tissue Growth FactorPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktAdipose-derived stem cells extracellular vesicles (ADSCs-EVs)AngiogenesisCellular communication network factor 2 (CCN2)Diabetic wound healingPI3K/AKT signaling pathway

Identifiers

PMID40518546
PMCPMC12168405

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.