Zhu Yiren, Chen Pinhua, Zhang Zhengchao, He XueYi, Wang Ruoli, Fang Qi, Xu Zhixian, He Wubing
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, 350001, China.
Department of Emergency Trauma Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, 350001, China.
Stem Cell Res Ther. 2025 Feb 25;16(1):93. doi: 10.1186/s13287-025-04241-5.
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.
ADSCs were genetically modified to achieve stable overexpression of aFGF. Varying doses of aFGF-ADSCs (1 × 10, 2 × 10, 3 × 10, 4 × 10) 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.
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 × 10 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).
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.
由于目前治疗方法的疗效有限，慢性糖尿病伤口构成了重大的临床挑战。本研究旨在探讨过表达酸性成纤维细胞生长因子（aFGF）的脂肪间充质干细胞（ADSCs）在大鼠糖尿病伤口愈合中的作用及潜在机制。
对ADSCs进行基因改造以实现aFGF的稳定过表达。将不同剂量的aFGF-ADSCs（1×10⁶、2×10⁶、3×10⁶、4×10⁶）注射到糖尿病大鼠伤口周围的肌肉组织中。我们评估了aFGF的表达及其对伤口愈合各个阶段的影响，包括血管生成、炎症反应、上皮化和胶原沉积。进行转录组测序以探索促进伤口愈合增强的潜在机制。
慢病毒转导成功诱导ADSCs中aFGF的稳定过表达。体内实验表明，不同剂量的aFGF-ADSCs以剂量依赖的方式显著增强了糖尿病大鼠的伤口愈合。3×10⁶个aFGF-ADSCs的剂量显示出最显著的效果。在3×10⁶个aFGF-ADSCs组中，aFGF、CD31和CD163的表达水平显著高于其他组（p<0.05），而CD86的表达显著较低（p<0.05）。
单剂量的aFGF-ADSCs全面改善了糖尿病大鼠伤口修复的各个方面，为治疗慢性糖尿病伤口提供了一种潜在的新方法。其作用机制包括促进血管生成、调节炎症反应、加速上皮化和优化胶原沉积。
