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Gingival-Derived Mesenchymal Stem Cells Protect Against Sepsis and Its Complications
Infection and Drug Resistance ( IF 2.9 ) Pub Date : 2021-08-22 , DOI: 10.2147/idr.s318304
Xishuai Wang 1, 2 , Hanan Song 1 , Shiyu Zhao 1 , Weijun Guan 1 , Yang Gao 3
Affiliation  

Objective: In the present study, we separated and characterized mouse gingival-derived mesenchymal stem cells (GMSCs) and investigated whether GMSCs can improve lipopolysaccharide (LPS)-induced sepsis and its complications.
Methods: Ninety-six ICR mice were randomly divided into the following groups: the control (Sham), LPS, and LPS + MSC groups. Mice received 5 mg/kg LPS intraperitoneally to induce sepsis. Histopathological micrographs illustrated organ injury. We detected systemic inflammation, blood glucose levels, and serum levels of high-mobility group box 1 (HMGB1) and lactate. In addition, pulmonary inflammation, lung permeability, and oxidative stress-related indicators in lung tissue were measured.
Results: We successfully separated a novel population of MSCs from mouse gingiva. These cells had MSC-associated properties, such as a typical fibroblast-like morphology, multiple differentiation potential, and certain phenotypes. Cell-based therapy using GMSCs significantly improved the survival rate, systemic inflammation, hypoglycemia, multiple organ dysfunction syndrome (MODS), and aortic injury during sepsis. GMSCs administration reduced pulmonary inflammation, lung permeability, and oxidative stress injury. GMSCs administration reduced neutrophil infiltration partly because GMSCs inhibited neutrophil chemoattractants tumor necrosis factor (TNF-α), C-X-C motif chemokine ligand (CXCL-1), and Interleukin (IL-8). GMSCs impaired LPS-induced HMGB1 and lactate release during sepsis.
Conclusion: GMSCs administration is a novel therapeutic strategy targeting aerobic glycolysis for the treatment of sepsis because GMSCs impair LPS-induced HMGB1 and lactate release. GMSCs alleviate lung injury partly because GMSCs exert immune effects, inhibit neutrophilic inflammation, and reduce oxidative stress injury.

Keywords: mesenchymal stem cells, sepsis, ALI, neutrophilic inflammation, oxidative stress, Warburg effect


中文翻译:

牙龈来源的间充质干细胞可预防脓毒症及其并发症

目的:在本研究中,我们分离和表征了小鼠牙龈来源的间充质干细胞(GMSCs),并研究了GMSCs是否可以改善脂多糖(LPS)诱导的脓毒症及其并发症。
方法:将96只ICR小鼠随机分为以下组:对照组(Sham)、LPS和LPS+MSC组。小鼠腹腔内接受 5 mg/kg LPS 以诱导败血症。组织病理学显微照片显示器官损伤。我们检测了全身炎症、血糖水平和高迁移率组框 1 (HMGB1) 和乳酸的血清水平。此外,还测量了肺组织中的肺部炎症、肺通透性和氧化应激相关指标。
结果:我们成功地从小鼠牙龈中分离出新的 MSCs 群。这些细胞具有 MSC 相关特性,例如典型的成纤维细胞样形态、多分化潜能和某些表型。使用 GMSCs 的基于细胞的治疗显着提高了脓毒症期间的存活率、全身炎症、低血糖、多器官功能障碍综合征 (MODS) 和主动脉损伤。GMSCs 给药减少了肺部炎症、肺通透性和氧化应激损伤。GMSCs 给药减少了中性粒细胞浸润,部分原因是 GMSCs 抑制了中性粒细胞趋化因子肿瘤坏死因子 (TNF-α)、CXC 基序趋化因子配体 (CXCL-1) 和白细胞介素 (IL-8)。GMSCs 在脓毒症期间损害 LPS 诱导的 HMGB1 和乳酸释放。
结论:GMSCs 给药是一种针对有氧糖酵解治疗脓毒症的新型治疗策略,因为 GMSCs 会损害 LPS 诱导的 HMGB1 和乳酸释放。GMSCs 减轻肺损伤的部分原因是 GMSCs 发挥免疫作用,抑制中性粒细胞炎症,减少氧化应激损伤。

关键词:间充质干细胞,脓毒症,ALI,中性粒细胞炎症,氧化应激,Warburg 效应
更新日期:2021-08-21
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