金纳米心肌补丁介导的VEGF高表达间充质干细胞促梗死心肌修复作用及机制研究

The vascular endothelial growth factor (VEGF) or bone marrow mesenchymal stem cells (MSCs) have been used to promote myocardial repair and vascular angiogenesis after myocardial infarction, but efficacy of the experiment is far from expected by clinical trials. The very few number and short life span of live cells transplanted are important part of the reasons.Our previous studies have successfully constructed a gold nanowired three-dimensional scaffold which can promote the adhesion and proliferation of stem cells. In this research,(1)we plan to construct an alternative cardiac patch composited with 3-dimensional gold nanowires and the VEGF gene-modified MSCs, to explore its protective effects on myocardial cells ,vascular endothelial cells and the homing effects for MSCs under hypoxia conditions in vitro;(2) to test neonatal cell contractile function under electrical stimulation; (3)to observe the formation of angiogenesis and myocardial structure on myocardial patch in the omentum; (4) to explore the homing effects and anti-apoptosis effects for MSCs under the gold nanowired patchs;(5)to further investigate the regeneration of myocardium in vivo on rat acute myocardial infarction models.This research will provide a new idea and method for promoting myocardial repair after myocardial infarction.

研究证实应用血管生长因子或骨髓间充质干细胞（MSCs）能够促进心肌梗死后血管新生及心肌修复，但临床试验结果却远小于预期。这与MSCs体内移植后存活率低以及存活时间短密切相关。在前期研究中,我们成功构建了含有金纳米线的三维纳米补丁,发现其能够促进骨髓间充质干细胞粘附和增殖。本研究拟:(1)体外构建VEGF基因修饰的MSCs三维金纳米心肌补丁，并评价其在低氧环境下对心肌细胞、血管内皮细胞的保护作用及MSCs的趋化功能；（2）体外检测新生心肌细胞电刺激下细胞收缩功能；（3）在大网膜上检测心肌补丁的血管新生和心肌结构的形成；（4）检测SDF-1/CXCR4通道阻断后细胞因子及上述功能变化，明确三维金纳米心肌补丁的干细胞归巢和抗凋亡作用，揭示三维金纳米补丁促心肌修复的作用机制；（5）进一步在大鼠心肌梗死模型上观察其促血管新生及对梗死心肌的修复作用，为心肌梗死后心肌修复提供新的思路和手段。

研究证实应用血管生长因子或骨髓间充质干细胞（MSCs）能够促进心肌梗死后血管新生及心肌修复,但存在移植后存活率低的问题。在前期研究中,我们成功构建了含有金纳米线的三维纳米补丁,发现其能够促进骨髓间充质干细胞粘附和增殖。在此基础上，本研究从体外构建VEGF基因修饰的MSCs三维金纳米心肌补丁，并评价了其在低氧环境下对心肌细胞、血管内皮细胞的保护作用及促进MSCs的趋化功能；体外检测金纳米心肌补丁对新生心肌细胞电刺激下细胞收缩功能；明确三维金纳米心肌补丁的干细胞归巢和抗凋亡作用。同时进一步在大鼠心肌梗死模型上观察其促血管新生及对梗死心肌的修复作用，为心肌梗死后心肌修复提供新的思路和手段。课题组共撰写并发表标注受本项目资助的SCI 文章7篇。并为进一步探索动脉粥样硬化内皮损伤血管的快速修复提供新的思路和研究方向。