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首页> 外文期刊>American Journal of Physiology >Stem cell conditioned medium Improves acute lung Injury in mice: in vivo evidence for stem cell paracrine action
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Stem cell conditioned medium Improves acute lung Injury in mice: in vivo evidence for stem cell paracrine action

机译：干细胞条件培养基可改善小鼠急性肺损伤：干细胞旁分泌作用的体内证据

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摘要

Mortality and morbidity of acute lung injury and acute respiratory distress syndrome remain high because of the lack of pharmacological therapies to prevent injury or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar macrophage (AM) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared with whole MSCs, lung fibroblasts, and fibroblast-CdM. Intra-tracheal MSCs and MSC-CdM significantly attenuated lipopolysac-charide (LPS)-induced lung neutrophil influx, lung edema, and lung injury as assessed by an established lung injury score. MSC-CdM increased arginase-1 activity and Yml expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhanced expression of Yml and decreased expression of inducible nitric oxide synthase compared with untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2 "healer" phenotype. Comparative multiplex analysis of MSC-and fibroblast-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, including insulin-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part via IGF-I.
机译：急性肺损伤和急性呼吸窘迫综合征的死亡率和发病率仍然很高，这是因为缺乏预防损伤或促进修复的药理疗法。尽管供体来源的细胞植入比例低，间充质干细胞（MSC）仍能在各种实验模型中预防肺损伤，这表明MSC通过旁分泌机制发挥其有益作用。我们假设MSC分泌的可溶性因子部分通过调节肺泡巨噬细胞（AM）功能来促进肺损伤的解决。我们测试了MSC来源条件培养基（CdM）与完整MSC，肺成纤维细胞和成纤维细胞CdM的治疗效果。气管内MSC和MSC-CdM可以显着减轻脂多糖（LPS）诱导的肺中性粒细胞流入，肺水肿和肺损伤，这已通过既定的肺损伤评分进行了评估。 MSC-CdM增加了LPS暴露的AM中的精氨酸酶1活性和Yml表达。在体内，与未治疗的LPS小鼠相比，LPS-MSC和LPS-MSC CdM肺的AMs增强了Yml的表达，并降低了诱导型一氧化氮合酶的表达。这表明，MSC-CdM将替代性的巨噬细胞激活促进为M2“修复”表型。 MSC-和成纤维细胞-CdM的比较多元分析表明，MSC-CdM包含几种可能赋予治疗益处的因子，包括胰岛素样生长因子I（IGF-1）。重组IGF-I部分复制了MSC-CdM的肺保护作用。总之，MSC通过旁分泌活动起作用。 MSC-CdM通过减轻肺部炎症并部分通过IGF-I促进伤口愈合/抗炎M2巨噬细胞表型来促进LPS诱导的肺损伤的解决。

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