Wan XX, Yan WT, He WH, Xiong K. Synergistic mechanism of adipose-derived stem cells in healing diabetic foot ulcers. World J Diabetes 2026; 17(5): 116210 [DOI: 10.4239/wjd.v17.i5.116210]
Corresponding Author of This Article
Kun Xiong, Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, No. 172 Tongzipo Road, Changsha 410013, Hunan Province, China. xiongkun2001@163.com
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Medicine, Research & Experimental
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May 15, 2026 (publication date) through May 14, 2026
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Publication Name
World Journal of Diabetes
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1948-9358
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Wan XX, Yan WT, He WH, Xiong K. Synergistic mechanism of adipose-derived stem cells in healing diabetic foot ulcers. World J Diabetes 2026; 17(5): 116210 [DOI: 10.4239/wjd.v17.i5.116210]
World J Diabetes. May 15, 2026; 17(5): 116210 Published online May 15, 2026. doi: 10.4239/wjd.v17.i5.116210
Synergistic mechanism of adipose-derived stem cells in healing diabetic foot ulcers
Kun Xiong, Wen-Hua He, Wei-Tao Yan, Xin-Xing Wan
Xin-Xing Wan, Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
Wei-Tao Yan, Kun Xiong, Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
Wen-Hua He, Department of Intensive Care Unit, Hunan Chest Hospital, Changsha 410000, Hunan Province, China
Wen-Hua He, Department of Cardiology, The Fourth Hospital of Changsha, Changsha 410000, Hunan Province, China
Author contributions: Wan XX wrote the original draft; Yan WT and He WH reviewed and edited this editorial; Xiong K was the senior author and provided supervision and validation of the writing; all authors have read and agreed to the published version of the manuscript.
Supported by National Natural Science Foundation of China, No. 82572869, No. 82372507, and No. 82172196; and Natural Science Foundation of Hunan Province, No. 2023JJ60015.
AI contribution statement: This manuscript was polished with the assistance of DeepSeek to enhance readability. The author has thoroughly reviewed, edited, and assumes full responsibility for the final content.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Kun Xiong, Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, No. 172 Tongzipo Road, Changsha 410013, Hunan Province, China. xiongkun2001@163.com
Received: November 5, 2025 Revised: December 22, 2025 Accepted: January 7, 2026 Published online: May 15, 2026 Processing time: 187 Days and 7.6 Hours
Abstract
Diabetic foot ulcers (DFUs) are a common complication of diabetes. The injection of mesenchymal stem cells (MSCs) has emerged as a potential therapeutic strategy for DFUs, and several related clinical cohort studies have been conducted. Our previous research found that MSCs derived from umbilical cord and bone marrow exhibit strong reparative abilities. When combined with endothelial progenitor cells, they promoted wound healing in several patients with refractory foot ulcers. In the study published in World Journal of Diabetes by Cao et al, they demonstrated that subcutaneous injection of 5 × 105 adipose-derived stem cells (ADSCs) into the foot yielded the best wound healing outcomes for DFUs. Further angiogenesis experiments confirmed that ADSCs promote vascularization by activating the PI3K-AKT pathway to enhance VEGF secretion. Additionally, ADSCs were shown to inhibit the overactivated Notch1 signaling pathway, thereby reducing inflammation and improving collagen deposition. This study provides valuable insights into the mechanisms by which ADSCs promote DFU healing and offers important evidence to support the clinical application of MSCs.
Core Tip: Although mesenchymal stem cells (MSCs) can be isolated and expanded from a variety of tissues, their regenerative efficacy for diabetic foot ulcers (DFUs) exhibits significant source-dependent variation, and the specific regulatory mechanisms involved remain incompletely understood. Cao et al demonstrated that subcutaneous injection of 5 × 105 adipose-derived stem cells (ADSCs) into the foot yielded the most effective wound healing outcomes for DFUs. Further angiogenesis experiments revealed that ADSCs promote blood vessel formation by activating the PI3K-AKT pathway to enhance VEGF secretion. Additionally, it was confirmed that ADSCs can suppress the overactivated Notch signaling pathway, thereby reducing local inflammatory responses and improving collagen deposition. This study not only elucidates the underlying molecular mechanisms by which ADSCs accelerate DFU healing but also provides critical evidence to support the clinical application of MSCs.
