急性肺损伤是一种破坏肺内皮和上皮屏障的急性炎症性疾病。在这项研究中，我们研究了通过在犬脂肪间充质干细胞上启动炎症细胞因子（例如肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ）获得的细胞外囊泡（EV），以改善其抗炎和/或免疫抑制作用。潜力和/或它们在体外减轻脂多糖诱导的肺损伤的能力。我们还探讨了上皮间质转化与引发的 EV 的炎症抑制作用之间的相关性。使用小 RNA 测序，我们证实 TNF-α 和 IFN-γ 引发的犬脂肪间充质干细胞的 EV 中 miR-16 和 miR-502 显着增加。在脂多糖诱导的肺损伤模型中分析促炎细胞因子和抗炎细胞因子，我们发现 EV 抗炎作用在用炎性细胞因子启动后得到改善。从引发的干细胞中获得的 EV 可有效抑制肺损伤模型中的内皮细胞向间质细胞的转变。我们的结果提出了一种潜在的治疗方法，利用从经 TNF-α 和 IFN-γ 引发的脂肪间充质干细胞获得的 EV 来对抗肺部炎症和内皮向间质转化。版权所有 © 2024 Lee、Jeong、Kim、Yun、Ahn、Chung 和 An。

Acute lung injury is an acute inflammation disorder that disrupts the lung endothelial and epithelial barriers. In this study, we investigated the extracellular vesicles (EVs) obtained via priming inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ on canine adipose mesenchymal stem cells in improving their anti-inflammatory and/or immunosuppressive potential, and/or their ability to alleviate lipopolysaccharide-induced lung injury in vitro. We also explored the correlation between epithelial-to-mesenchymal transition and the inflammatory repressive effect of primed EVs. Using small RNA-Seq, we confirmed that miR-16 and miR-502 significantly increased in EVs from TNF-α and IFN-γ-primed canine adipose mesenchymal stem cells. The pro and anti-inflammatory cytokines were analyzed in a lipopolysaccharide-induced lung injury model and we found that the EV anti-inflammatory effect improved on priming with inflammatory cytokines. EVs obtained from primed stem cells effectively suppress endothelial-to-mesenchymal transition in a lung injury model. Our results suggest a potential therapeutic approach utilizing EVs obtained from adipose mesenchymal stem cells primed with TNF-α and IFN-γ against lung inflammation and endothelial to mesenchymal transition.Copyright © 2024 Lee, Jeong, Kim, Yun, Ahn, Chung and An.