aFGF gene-modified adipose-derived mesenchymal stem cells promote healing of full-thickness skin defects in diabetic rats

Abstract Background Chronic diabetic wounds pose a significant clinical challenge due to the limited efficacy of current treatments. This study aimed to investigate the role and potential mechanisms of adipose-derived mesenchymal stem cells (ADSCs) overexpressing acidic fibroblast growth factor (aFG...

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Main Authors: Yiren Zhu, Pinhua Chen, Zhengchao Zhang, XueYi He, Ruoli Wang, Qi Fang, Zhixian Xu, Wubing He
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-025-04241-5
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author Yiren Zhu
Pinhua Chen
Zhengchao Zhang
XueYi He
Ruoli Wang
Qi Fang
Zhixian Xu
Wubing He
author_facet Yiren Zhu
Pinhua Chen
Zhengchao Zhang
XueYi He
Ruoli Wang
Qi Fang
Zhixian Xu
Wubing He
author_sort Yiren Zhu
collection DOAJ
description Abstract Background Chronic diabetic wounds pose a significant clinical challenge due to the limited efficacy of current treatments. This study aimed to investigate the role and potential mechanisms of adipose-derived mesenchymal stem cells (ADSCs) overexpressing acidic fibroblast growth factor (aFGF) in diabetic wound healing in a rat model. Methods ADSCs were genetically modified to achieve stable overexpression of aFGF. Varying doses of aFGF-ADSCs (1 × 106, 2 × 106, 3 × 106, 4 × 106) were injected into the muscular tissue surrounding diabetic rat wounds. We assessed aFGF expression and its impact on various stages of wound healing, including angiogenesis, inflammatory response, epithelialization, and collagen deposition. Transcriptomic sequencing was performed to explore the underlying mechanisms driving enhanced wound healing. Results Lentiviral transduction successfully induced stable aFGF overexpression in ADSCs. In vivo experiments revealed that varying doses of aFGF-ADSCs markedly enhanced wound healing in diabetic rats in a dose-dependent manner. The dose of 3 × 10⁶ aFGF-ADSCs demonstrated the most significant effect. In the 3 × 106 aFGF-ADSCs group, expression levels of aFGF, CD31, and CD163 were significantly higher than in other groups (p < 0.05), while CD86 expression was significantly lower (p < 0.05). Conclusion Single doses of aFGF-ADSCs comprehensively improved various aspects of wound repair in diabetic rats, offering a potential new approach for treating chronic diabetic wounds. The mechanism of action involves promoting angiogenesis, modulating inflammatory responses, accelerating epithelialization, and optimizing collagen deposition.
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spelling doaj-art-125daebd3f8e4fa281c114836ae808672025-08-20T02:16:34ZengBMCStem Cell Research & Therapy1757-65122025-02-0116111510.1186/s13287-025-04241-5aFGF gene-modified adipose-derived mesenchymal stem cells promote healing of full-thickness skin defects in diabetic ratsYiren Zhu0Pinhua Chen1Zhengchao Zhang2XueYi He3Ruoli Wang4Qi Fang5Zhixian Xu6Wubing He7Shengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityAbstract Background Chronic diabetic wounds pose a significant clinical challenge due to the limited efficacy of current treatments. This study aimed to investigate the role and potential mechanisms of adipose-derived mesenchymal stem cells (ADSCs) overexpressing acidic fibroblast growth factor (aFGF) in diabetic wound healing in a rat model. Methods ADSCs were genetically modified to achieve stable overexpression of aFGF. Varying doses of aFGF-ADSCs (1 × 106, 2 × 106, 3 × 106, 4 × 106) were injected into the muscular tissue surrounding diabetic rat wounds. We assessed aFGF expression and its impact on various stages of wound healing, including angiogenesis, inflammatory response, epithelialization, and collagen deposition. Transcriptomic sequencing was performed to explore the underlying mechanisms driving enhanced wound healing. Results Lentiviral transduction successfully induced stable aFGF overexpression in ADSCs. In vivo experiments revealed that varying doses of aFGF-ADSCs markedly enhanced wound healing in diabetic rats in a dose-dependent manner. The dose of 3 × 10⁶ aFGF-ADSCs demonstrated the most significant effect. In the 3 × 106 aFGF-ADSCs group, expression levels of aFGF, CD31, and CD163 were significantly higher than in other groups (p < 0.05), while CD86 expression was significantly lower (p < 0.05). Conclusion Single doses of aFGF-ADSCs comprehensively improved various aspects of wound repair in diabetic rats, offering a potential new approach for treating chronic diabetic wounds. The mechanism of action involves promoting angiogenesis, modulating inflammatory responses, accelerating epithelialization, and optimizing collagen deposition.https://doi.org/10.1186/s13287-025-04241-5aFGFADSCsWound healingAngiogenesisInflammatory modulation
spellingShingle Yiren Zhu
Pinhua Chen
Zhengchao Zhang
XueYi He
Ruoli Wang
Qi Fang
Zhixian Xu
Wubing He
aFGF gene-modified adipose-derived mesenchymal stem cells promote healing of full-thickness skin defects in diabetic rats
Stem Cell Research & Therapy
aFGF
ADSCs
Wound healing
Angiogenesis
Inflammatory modulation
title aFGF gene-modified adipose-derived mesenchymal stem cells promote healing of full-thickness skin defects in diabetic rats
title_full aFGF gene-modified adipose-derived mesenchymal stem cells promote healing of full-thickness skin defects in diabetic rats
title_fullStr aFGF gene-modified adipose-derived mesenchymal stem cells promote healing of full-thickness skin defects in diabetic rats
title_full_unstemmed aFGF gene-modified adipose-derived mesenchymal stem cells promote healing of full-thickness skin defects in diabetic rats
title_short aFGF gene-modified adipose-derived mesenchymal stem cells promote healing of full-thickness skin defects in diabetic rats
title_sort afgf gene modified adipose derived mesenchymal stem cells promote healing of full thickness skin defects in diabetic rats
topic aFGF
ADSCs
Wound healing
Angiogenesis
Inflammatory modulation
url https://doi.org/10.1186/s13287-025-04241-5
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