Chen Liang, Liu Yuanqing, Yu Chenhao, Cao Pei, Ma Yiming, Geng Yiran, Cai Yu, Zhang Yong, Liu Jia, Li Yang, Luan Qingxian
Department of Periodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, No. 22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, People's Republic of China.
First Clinical Division, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, No. 22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, People's Republic of China.
Stem Cell Res Ther. 2025 May 2;16(1):223. doi: 10.1186/s13287-025-04327-0.
Periodontitis is a chronic inflammatory disease and macrophages play a pivotal role in the progression of periodontitis. Mesenchymal stem cells (MSCs) have emerged as potential therapeutic agents for the treatment of periodontitis due to their immunomodulatory properties and capacity for tissue regeneration. Compared to conventionally derived MSCs, induced pluripotent stem cell-derived MSCs (iMSCs) offer distinct advantages as promising candidates for MSC-based therapies, owing to their non-invasive acquisition methods and virtually unlimited availability. This study aims to investigate the effects and mechanisms of iMSCs in modulating macrophage polarization and alleviating periodontitis-related alveolar bone loss.
iMSCs were generated from iPSCs and characterized for differentiation potential. The effects of iMSCs on macrophage polarization were evaluated using THP-1-derived macrophages under inflammatory conditions (LPS and IFN-γ stimulation). Co-culture assays, cytokine analysis, reactive oxygen species (ROS) detection, transcriptomic analysis, flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot analysis were performed to elucidate the underlying mechanisms. The therapeutic potential of iMSCs was assessed in a ligature-induced periodontitis mouse model using micro-CT, histological analysis, and immunofluorescence staining.
iMSCs inhibit M1 macrophage polarization through the suppression of the NF-κB signaling pathway. Additionally, iMSCs reduce the production of pro-inflammatory cytokines (IL-1β, IL-17) and reactive oxygen species (ROS), while enhancing the secretion of anti-inflammatory cytokines (IL-10) and growth factors (VEGF), thereby improving the inflammatory microenvironment. Under inflammatory conditions, iMSCs preserve the osteogenic potential of periodontal ligament stem cells (PDLSCs) and alleviate alveolar bone loss in mice with periodontitis. In vivo, iMSCs reduce the number of M1 macrophages and inhibit the activation of NF-κB in periodontal tissues, supporting their anti-inflammatory and immunomodulatory effects.
iMSCs demonstrate significant therapeutic potential in periodontitis by modulating macrophage polarization, reducing oxidative stress, and mitigating alveolar bone loss associated with the disease. These findings provide new insights into the mechanisms of iMSCs and their application as cell-based therapies for periodontal diseases.
牙周炎是一种慢性炎症性疾病，巨噬细胞在牙周炎的进展中起关键作用。间充质干细胞（MSCs）因其免疫调节特性和组织再生能力，已成为治疗牙周炎的潜在治疗剂。与传统来源的MSCs相比，诱导多能干细胞来源的MSCs（iMSCs）因其非侵入性获取方法和几乎无限的可用性，作为基于MSCs治疗的有前途的候选者具有明显优势。本研究旨在探讨iMSCs在调节巨噬细胞极化和减轻牙周炎相关牙槽骨丧失中的作用及机制。
从诱导多能干细胞（iPSCs）中生成iMSCs，并对其分化潜能进行表征。在炎症条件下（脂多糖和干扰素-γ刺激），使用THP-1来源的巨噬细胞评估iMSCs对巨噬细胞极化的影响。进行共培养试验、细胞因子分析、活性氧（ROS）检测、转录组分析、流式细胞术、逆转录定量聚合酶链反应（RT-qPCR）和蛋白质印迹分析以阐明潜在机制。使用显微计算机断层扫描（micro-CT）、组织学分析和免疫荧光染色，在结扎诱导的牙周炎小鼠模型中评估iMSCs的治疗潜力。
iMSCs通过抑制核因子-κB（NF-κB）信号通路抑制M1巨噬细胞极化。此外，iMSCs减少促炎细胞因子（白细胞介素-1β、白细胞介素-17）和活性氧（ROS）的产生，同时增强抗炎细胞因子（白细胞介素-10）和生长因子（血管内皮生长因子）的分泌，从而改善炎症微环境。在炎症条件下，iMSCs保留牙周膜干细胞（PDLSCs）的成骨潜能，并减轻牙周炎小鼠的牙槽骨丧失。在体内，iMSCs减少牙周组织中M1巨噬细胞的数量并抑制NF-κB的激活，支持其抗炎和免疫调节作用。
iMSCs通过调节巨噬细胞极化、降低氧化应激和减轻与该疾病相关的牙槽骨丧失，在牙周炎中显示出显著的治疗潜力。这些发现为iMSCs的机制及其作为牙周疾病基于细胞的治疗方法的应用提供了新的见解。
