Gao Xiaoli, Liu Zhiqiang, Wang Zuomin
Department of Stomatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China.
J Inflamm Res. 2023 Apr 8;16:1497-1508. doi: 10.2147/JIR.S402794. eCollection 2023.
Dental pulp stem cells (DPSCs) are considered excellent candidates for stem cell-based tissue regeneration. In this study, we aimed to evaluate the therapeutic effect of DPSCs in a mouse chronic obstructive pulmonary disease (COPD) model and to explore whether DPSCs reduce lung inflammation and oxidative stress by regulating the nuclear factor erythroid-2 related factor-2 (Nrf2) signaling pathway.
DPSCs were isolated from dental pulp tissue by the tissue block method. Emphysema of C57BL/6 mice was induced by endotracheal administration of porcine pancreatic elastase (PPE). Then, the DPSCs were injected into the lungs through the trachea, and after 3 weeks of stem cell treatment, various efficacy tests were performed. The AniRes2005 animal lung function analytic system was used to detect lung function. Hematoxylin-eosin staining (H&E) and Victoria blue staining was used to assess emphysema severity. The animal tissues were detected by Western blot, RT‒qPCR, ELISA and oxidative stress related detection.
In experimental COPD models, DPSCs transplantation improved lung function, body weight, and emphysema-like changes better than bone marrow mesenchyml stem cells (BM-MSCs). Compared with the COPD group, the levels of IL-1β, TNF-α and IL-6 in lung tissue and bronchoalveolar lavage fluid (BALF) were decreased after transplantation of DPSCs. DPSCs may be associated with lower malondialdehyde (MDA) levels, and higher catalase (CAT) and glutathione (GSH) levels. Western blot results showed that the expression of Nrf2 and its downstream factors increased after transplantation of DPSCs.
The current study showed that DPSCs had good performance in the treatment of a mouse COPD model and could be a promising option for stem cell therapy. DPSCs may play antioxidant and anti-inflammatory roles in COPD by activating the Nrf2 signaling pathway.
牙髓干细胞（DPSCs）被认为是基于干细胞的组织再生的优秀候选者。在本研究中，我们旨在评估DPSCs在小鼠慢性阻塞性肺疾病（COPD）模型中的治疗效果，并探讨DPSCs是否通过调节核因子红细胞2相关因子2（Nrf2）信号通路来减轻肺部炎症和氧化应激。
采用组织块法从牙髓组织中分离DPSCs。通过气管内给予猪胰弹性蛋白酶（PPE）诱导C57BL/6小鼠肺气肿。然后，将DPSCs经气管注入肺内，在干细胞治疗3周后，进行各项疗效测试。使用AniRes2005动物肺功能分析系统检测肺功能。苏木精-伊红染色（H&E）和维多利亚蓝染色用于评估肺气肿严重程度。通过蛋白质免疫印迹法、逆转录-定量聚合酶链反应、酶联免疫吸附测定和氧化应激相关检测对动物组织进行检测。
在实验性COPD模型中，DPSCs移植在改善肺功能、体重和肺气肿样改变方面比骨髓间充质干细胞（BM-MSCs）更好。与COPD组相比，DPSCs移植后肺组织和支气管肺泡灌洗液（BALF）中白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平降低。DPSCs可能与较低的丙二醛（MDA）水平以及较高的过氧化氢酶（CAT）和谷胱甘肽（GSH）水平有关。蛋白质免疫印迹结果显示，DPSCs移植后Nrf2及其下游因子的表达增加。
当前研究表明，DPSCs在治疗小鼠COPD模型中表现良好，可能是干细胞治疗的一个有前景的选择。DPSCs可能通过激活Nrf2信号通路在COPD中发挥抗氧化和抗炎作用。
