Mesenchymal stem cells (MSCs) have demonstrated remarkable therapeutic promise for acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS). MSC secretomes contain various immunoregulatory mediators that modulate both innate and adaptive immune responses. Priming MSCs has been widely considered to boost their therapeutic efficacy for a variety of diseases. Prostaglandin E2 (PGE2) plays a vital role in physiological processes that mediate the regeneration of injured organs. This work utilized PGE2 to prime MSCs and investigated their therapeutic potential in ALI models. MSCs were obtained from human placental tissue. MSCs were transduced with firefly luciferase (Fluc)/eGFP fusion protein for real-time monitoring of MSC migration. Comprehensive genomic analyses explored the therapeutic effects and molecular mechanisms of PGE2-primed MSCs in LPS-induced ALI models. Our results demonstrated that PGE2-MSCs effectively ameliorated lung injury and decreased total cell numbers, neutrophils, macrophages, and protein levels in bronchoalveolar lavage fluid (BALF). Meanwhile, treating ALI mice with PGE2-MSCs dramatically reduced histopathological changes and proinflammatory cytokines while increasing anti-inflammatory cytokines. Furthermore, our findings supported that PGE2 priming improved the therapeutic efficacy of MSCs through M2 macrophage polarization. PGE2-MSC therapy significantly reduced the severity of LPS-induced ALI in mice by modulating macrophage polarization and cytokine production. This strategy boosts the therapeutic efficacy of MSCs in cell-based ALI therapy.

中文翻译：

---

PGE2 启动间充质干细胞通过巨噬细胞免疫调节对 LPS 诱导的急性肺损伤 (ALI) 具有优异的保护作用

间充质干细胞 (MSC) 已证明对急性肺损伤 (ALI) 及其严重形式急性呼吸窘迫综合征 (ARDS) 具有显着的治疗前景。MSC 分泌蛋白组包含多种免疫调节介质，可调节先天性和适应性免疫反应。启动 MSCs 已被广泛认为可以提高其对多种疾病的治疗效果。前列腺素 E2 (PGE2) 在介导受损器官再生的生理过程中起着至关重要的作用。这项工作利用 PGE2 启动 MSC，并研究了它们在 ALI 模型中的治疗潜力。MSCs 是从人胎盘组织中获得的。用萤火虫荧光素酶 (Fluc)/eGFP 融合蛋白转导 MSC，以实时监测 MSC 迁移。综合基因组分析探索了 PGE2 引发的 MSCs 在 LPS 诱导的 ALI 模型中的治疗效果和分子机制。我们的研究结果表明，PGE2-MSCs 可有效改善肺损伤并降低支气管肺泡灌洗液 (BALF) 中的总细胞数、中性粒细胞、巨噬细胞和蛋白质水平。同时，用 PGE2-MSCs 治疗 ALI 小鼠可显着减少组织病理学变化和促炎细胞因子，同时增加抗炎细胞因子。此外，我们的研究结果支持 PGE2 启动通过 M2 巨噬细胞极化提高了 MSCs 的治疗效果。PGE2-MSC 疗法通过调节巨噬细胞极化和细胞因子的产生，显着降低了 LPS 诱导的小鼠 ALI 的严重程度。这种策略提高了 MSCs 在基于细胞的 ALI 治疗中的治疗效果。