Preconditioning by Mitochondrial Reactive Oxygen Species Improves the Proangiogenic Potential of Adipose-Derived Cells-Based Therapy
Preconditioning by Mitochondrial Reactive Oxygen Species Improves the Proangiogenic Potential of Adipose-Derived Cells-Based Therapy
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DOI：
10.1161/atvbaha.109.188318
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发表时间：
2009-07-01
影响因子：
8.7
通讯作者：
Casteilla, Louis
中科院分区：
文献类型：
--
作者：
Carriere, Audrey;Ebrahimian, Teni G.;Casteilla, Louis
目的-脂肪源性基质细胞（ADSC）移植可刺激实验性缺血性损伤后的新血管形成。 ADSC 的促血管生成潜力可能是由其分化为内皮细胞并产生多种血管生成和抗凋亡因子的能力介导的。线粒体活性氧 (ROS) 已被证明可以控制 ADSC 分化。因此，我们假设线粒体ROS的产生可能会改变ADSC的促血管生成特性。方法和结果-使用药理学策略（线粒体抑制剂、抗霉素和鱼藤酮，有或没有抗氧化剂）使我们能够特异性、精确地调节ADSC中线粒体ROS的产生。我们发现，在将 ADSC 注射到缺血后肢之前，短暂刺激 ADSC 中线粒体 ROS 的生成，可显着改善缺血区域的血运重建和 ADSC 衍生的 CD31 阳性细胞的数量。体外，线粒体 ROS 的产生增加了促血管生成因子和抗凋亡因子 VEGF 和 HGF 的分泌，但不影响 ADSC 分化为内皮细胞的能力。此外，线粒体ROS诱导的ADSC预处理极大地保护ADSC免受氧化应激诱导的细胞死亡。结论-我们的研究表明，通过适度线粒体ROS生成进行的体外预处理强烈增加了体内ADSC的促血管生成特性，并强调了线粒体ROS在ADSC命运中的关键作用。 （动脉硬化血栓 Vasc Biol.2009；29：1093-1099。）
Objective-Transplantation of adipose-derived stroma cells (ADSCs) stimulates neovascularization after experimental ischemic injury. ADSC proangiogenic potential is likely mediated by their ability to differentiate into endothelial cells and produce a wide array of angiogenic and antiapoptotic factors. Mitochondrial reactive oxygen species (ROS) have been shown to control ADSC differentiation. We therefore hypothesized that mitochondrial ROS production may change the ADSC proangiogenic properties.Methods and Results-The use of pharmacological strategies (mitochondrial inhibitors, antimycin, and rotenone, with or without antioxidants) allowed us to specifically and precisely modulate mitochondrial ROS generation in ADSCs. We showed that transient stimulation of mitochondrial ROS generation in ADSCs before their injection in ischemic hindlimb strongly improved revascularization and the number of ADSC-derived CD31-positive cells in ischemic area. Mitochondrial ROS generation increased the secretion of the proangiogenic and antiapoptotic factors, VEGF and HGF, but did not affect ADSC ability to differentiate into endothelial cells, in vitro. Moreover, mitochondrial ROS-induced ADSC preconditioning greatly protect ADSCs against oxidative stress-induced cell death.Conclusion-Our study demonstrates that in vitro preconditioning by moderate mitochondrial ROS generation strongly increases in vivo ADSC proangiogenic properties and emphasizes the crucial role of mitochondrial ROS in ADSC fate. (Arterioscler Thromb Vasc Biol. 2009; 29: 1093-1099.)