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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2025; 16(11): 109859
Published online Nov 15, 2025. doi: 10.4239/wjd.v16.i11.109859
Published online Nov 15, 2025. doi: 10.4239/wjd.v16.i11.109859
Optimizing adipose-derived stem cell therapy for diabetic foot ulcers
Jing Cao, Zi-Chao Liu, Wen-Qiang An, Xin Zhang, Li-Jie Li, Hai-Lian Ji, Yue-Mei Yang, Department of Research and Development, Beijing AegleStem Therapeutics Co., Ltd, Beijing 102600, China
Sen Zhang, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China
Xiao Long, Department of Plastic and Reconstructive Surgery, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
Co-first authors: Jing Cao and Zi-Chao Liu.
Co-corresponding authors: Xiao Long and Yue-Mei Yang.
Author contributions: Cao J and Liu ZC contributed equally as co-first authors; Cao J designed the study and wrote the manuscript; Liu ZC, An WQ, and Zhang X performed the experiments; Zhang S, Li LJ, and Ji HL acquired and analyzed data; Long X and Yang YM designed the study, interpreted the data, and made equal contributions as co-corresponding authors. All authors read and approved the final manuscript.
Supported by The Zhongguancun National Independent Innovation Demonstration Zone Industrial Ecosystem Cultivation Project, No. 20220468089.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, No. I-25ZM0035.
Institutional animal care and use committee statement: Ethics approval for mouse experiments was granted by the Ethics Committee of Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, No. 00009780. Ethical approval for the rat experiments was granted by the Ethics Committee of Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, No. 00009781.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data generated or analyzed during this study are available from the corresponding author upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yue-Mei Yang, PhD, Department of Research and Development, Beijing AegleStem Therapeutics Co., Ltd, No. 1 Yuanping North Road, Daxing District, Beijing 102600, China. maeyang@aeglestem.com
Received: June 3, 2025
Revised: July 9, 2025
Accepted: October 10, 2025
Published online: November 15, 2025
Processing time: 167 Days and 8.1 Hours
Revised: July 9, 2025
Accepted: October 10, 2025
Published online: November 15, 2025
Processing time: 167 Days and 8.1 Hours
Core Tip
Core Tip: This study systematically evaluated the dose-response relationship, administration route, persistence, and mechanisms of adipose-derived mesenchymal stem cells (ADSCs) in diabetic foot ulcer healing. Subcutaneous injection of 5 × 105 ADSCs showed optimal efficacy with prolonged retention. Mechanistically, ADSCs restore the phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin-hypoxia-inducible factor-1α-vascular endothelial growth factor pathway to improve angiogenesis and inhibit Notch signaling pathway overactivation to reduce inflammation and enhance collagen deposition. These results provide critical insights into the optimization of ADSC-based therapies and offer a promising approach for treating chronic diabetic wounds.