Identification of paracrine factors from mesenchaymal stem cell for protection and treatment against lung injury

以前的研究表明，间充质基质细胞(MSCs)通过上调和分泌STC1(stanniocalcin-1)来促进细胞存活。这项研究表明，MSC来源的STC1通过解偶联氧化磷酸化，减少细胞内活性氧物种(ROS)，并将代谢转向更具糖酵解的代谢谱来促进肺癌细胞的存活。MSC来源的STc1以STc1依赖的方式上调受损的A549细胞解偶联蛋白2(UCP2)。UCP2基因敲除降低了骨髓间充质干细胞和重组STC1(RSTC1)在A549群体中减少细胞死亡的能力。RSTC1处理的A549细胞表现出ROS水平降低，线粒体膜电位降低，乳酸生成增加，这一切都依赖于UCP2的上调。我们的数据表明，MSCs可以通过STC1调节线粒体呼吸来促进细胞存活。

Previous studies have demonstrated that mesenchymal stromal cells(MSCs)enhance cell survival through upregulation and secretion of stanniocalcin-1(STC1). This study shows that MSC-derived STC1 promotes survival of lung cancer cells by uncoupling oxidative phosphorylation, reducing intracellular reactive oxygen species(ROS), and shifting metabolism towards a more glycolytic metabolic profile. MSC-derived STC1 upregulated uncoupling protein 2(UCP2)in injured A549 cells in an STC1-dependent manner. Knockdown of UCP2 reduced the ability of MSCs and recombinant STC1(rSTC1)to reduce cell death in the A549 population. rSTC1-treated A549 cells displayed decreased levels of ROS, mitochondrial membrane potential(MMP), and increased lactate production, all of which were dependent on the upregulation of UCP2. Our data suggest that MSCs can promote cell survival by regulating mitochondrial respiration via STC1.