Udartseva Olga O, Lobanova Margarita V, Andreeva Elena R, Buravkov Sergey V, Ogneva Irina V, Buravkova Ludmila B
Institute of Biomedical Problems, Russian Academy of Science, Khoroshevskoe Shosse 76A, Moscow 123007, Russia.
Lomonosov Moscow State University, Faculty of Fundamental Medicine, Lomonosovsky Prospect 31-5, Moscow 117192, Russia.
Stem Cells Int. 2016;2016:7260562. doi: 10.1155/2016/7260562. Epub 2016 Dec 28.
The ability of mesenchymal stromal (stem) cells (MSCs) to be mobilised from their local depot towards sites of injury and to participate in tissue repair makes these cells promising candidates for cell therapy. Physiological O tension in an MSC niche in vivo is about 4-7%. However, most in vitro studies of MSC functional activity are performed at 20% O. Therefore, this study focused on the effects of short-term hypoxic stress (0.1% O, 24 h) on adipose tissue-derived MSC motility at tissue-related O level. No significant changes in integrin expression were detected after short-term hypoxic stress. However, O deprivation provoked vimentin disassembly and actin polymerisation and increased cell stiffness. In addition, hypoxic stress induced the downregulation of , and expression, the products of which are known to be involved in leading edge formation and cell translocation. These changes were accompanied by the attenuation of targeted and nontargeted migration of MSCs after short-term hypoxic exposure, as demonstrated in scratch and transwell migration assays. These results indicate that acute hypoxic stress can modulate MSC function in their native milieu, preventing their mobilisation from sites of injury.
间充质基质(干)细胞(MSC)从其局部储存库向损伤部位迁移并参与组织修复的能力,使这些细胞成为细胞治疗的有希望的候选者。体内MSC生态位中的生理氧张力约为4-7%。然而,大多数关于MSC功能活性的体外研究是在20%氧气条件下进行的。因此,本研究聚焦于在与组织相关的氧水平下,短期低氧应激(0.1%氧气,24小时)对脂肪组织来源的MSC迁移能力的影响。短期低氧应激后未检测到整合素表达的显著变化。然而,缺氧导致波形蛋白解聚和肌动蛋白聚合,并增加细胞硬度。此外,低氧应激诱导了 、 和 表达的下调,其产物已知参与前缘形成和细胞移位。如划痕和Transwell迁移试验所示,这些变化伴随着短期低氧暴露后MSC靶向和非靶向迁移的减弱。这些结果表明,急性低氧应激可在其天然环境中调节MSC功能,阻止其从损伤部位迁移。