Profound Actions of an Agonist of Growth Hormone-Releasing Hormone on Angiogenic Therapy by Mesenchymal Stem Cells.
Profound Actions of an Agonist of Growth Hormone-Releasing Hormone on Angiogenic Therapy by Mesenchymal Stem Cells.
复制标题
DOI：
10.1161/atvbaha.116.307126
复制
发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Ma Q;Xia X;Tao Q;Lu K;Shen J;Xu Q;Hu X;Tang Y;Block NL;Webster KA;Schally AV;Wang J;Yu H
细胞治疗的效率受到细胞存活和植入不良的限制。在这里，我们研究了生长激素释放激素激动剂JI-34对小鼠严重肢体缺血模型中间充质干细胞（MSCs）存活和血管生成治疗的影响。将小鼠骨髓来源的MSC与或不与10−8 mol/L JI-34孵育24小时。然后将MSCs暴露于缺氧和血清剥夺，以检测预处理对细胞凋亡、迁移和管形成的影响。在体内，通过股动脉结扎诱导严重肢体缺血。术后给予50μl磷酸盐缓冲液或1×106个MSCs或1×106个JI-34预处理的MSCs。用JI-34处理MSC改善MSC的活力和移动性，并显著增强其促进体外内皮管形成的能力。这些作用被STAT 3的磷酸化和核转位增加所抵消。在体内，与未经处理的MSC相比，JI-34预处理增强了MSC向缺血后肢肌肉的植入，并增强了再灌注和肢体挽救。在接受用JI-34处理的MSC的缺血肌肉中检测到显著更多的脉管系统和增殖的CD 31+和CD 34+细胞。我们的研究证明了JI-34通过增加MSC的活力和流动性来显著改善后肢缺血中的治疗性血管生成的新作用。这些发现支持了进一步的研究，以探索生长激素释放激素激动剂在缺血管理中增强细胞疗法的全部潜力。
The efficiency of cell therapy is limited by poor cell survival and engraftment. Here we studied the effect of the growth hormone-releasing hormone agonist, JI-34, on mesenchymal stem cells (MSCs) survival and angiogenic therapy in a mouse model of critical limb ischemia. Mouse bone marrow-derived MSCs were incubated with or without 10−8 mol/L JI-34 for 24 hours. MSCs were then exposed to hypoxia and serum deprivation to detect the effect of preconditioning on cell apoptosis, migration and tube formation. For in vivo, critical limb ischemia was induced by femoral artery ligation. After surgery, mice were received 50μl phosphate buffer saline or with 1×106 MSCs or with 1×106 JI-34 preconditioned MSCs. Treatment of MSCs with JI-34 improved MSCs viability and mobility and markedly enhanced their capability to promote endothelial tube formation in vitro. These effects were paralleled by increased phosphorylation and nuclear translocation of STAT3. In vivo, JI-34 pre-treatment enhanced the engraftment of MSCs into ischemic hindlimb muscles and augmented reperfusion and limb salvage compared with untreated MSCs. Significantly more vasculature and proliferating CD31+ and CD34+ cells were detected in ischemic muscles that received MSCs treated with JI-34. Our studies demonstrate a novel role for JI-34 to markedly improve therapeutic angiogenesis in hindlimb ischemia by increasing the viability and mobility of MSCs. These findings support additional studies to explore the full potential of Growth hormone-releasing hormone agonists to augment cell therapy in the management of ischemia.