Lai Fangyuan, Dai Shijie, Zhao Ye, Sun Yi
Center for Plastic & Reconstructive Surgery, Department of Plastic & Reconstructive Surgery, Zhejiang Provincial People's Hospital （Affiliated People's Hospital, Hangzhou Medical College）, Hangzhou, Zhejiang, China.
College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Injury. 2023 Feb 13. doi: 10.1016/j.injury.2023.02.027.
Adipose-derived stem cells (ADSCs) have been widely proven to facilitate wound healing. Our study aimed to estimate the influence of combined ADSCs and platelet-derived growth factor-BB (PDGF-BB) on wound healing. We utilized 4 healthy SD rats to isolate ADSCs. Platelet-rich plasma (PRP) was acquired utilizing a two-step centrifugation technology. The role of PRP, PDGF-BB, and PDGF-BB combined with a PI3k inhibitor LY294002 on the viability, migration, and PTEN/AKT pathway in ADSCs were examined utilizing CCK-8, Transwell, and western blot assays. Then, we constructed an open trauma model in SD rats. Effects of ADSCs treated with PDGF-BB on pathological changes, CD31, and PTEN/AKT pathway of wound closure were assessed by hematoxylin & eosin (H&E) staining, Masson staining, immunohistochemical, and western blot assays, respectively. PRP and PDGF-BB intensified the viability and migration of ADSCs by modulating the PTEN/AKT pathway. Interestingly, LY294002 reversed the role of PDGF-BB on ADSCs. In vivo experiments, combined intervention with ADSCs plus PDGF-BB/PRP facilitated wound closure and ameliorated histological injury. Moreover, combined intervention with ADSCs and PDGF-BB attenuated the PTEN level and elevated the CD31 level as well as the ratio of p-AKT/AKT in the skin tissues. A combination of ADSCs and PDGF-BB facilitated wound healing might associate with the regulation of the PTEN/AKT pathway.
脂肪来源干细胞（ADSCs）已被广泛证明可促进伤口愈合。我们的研究旨在评估ADSCs与血小板衍生生长因子-BB（PDGF-BB）联合应用对伤口愈合的影响。我们使用4只健康的SD大鼠分离ADSCs。利用两步离心技术获取富血小板血浆（PRP）。采用CCK-8、Transwell和蛋白质免疫印迹分析检测PRP、PDGF-BB以及PDGF-BB与磷脂酰肌醇-3激酶（PI3k）抑制剂LY294002联合应用对ADSCs活力、迁移及PTEN/AKT信号通路的作用。然后，我们在SD大鼠中构建开放性创伤模型。分别通过苏木精-伊红（H&E）染色、Masson染色、免疫组织化学和蛋白质免疫印迹分析评估经PDGF-BB处理的ADSCs对伤口愈合的病理变化、CD31以及PTEN/AKT信号通路的影响。PRP和PDGF-BB通过调节PTEN/AKT信号通路增强了ADSCs的活力和迁移能力。有趣的是，LY294002逆转了PDGF-BB对ADSCs的作用。在体内实验中，ADSCs与PDGF-BB/PRP联合干预促进了伤口闭合并改善了组织学损伤。此外，ADSCs与PDGF-BB联合干预降低了皮肤组织中PTEN水平，提高了CD31水平以及p-AKT/AKT比值。ADSCs与PDGF-BB联合应用促进伤口愈合可能与PTEN/AKT信号通路的调节有关。
