Effects of Matrix Metalloproteinases on the Performance of Platelet Fibrin Gel Spiked With Cardiac Stem Cells in Heart Repair.
Effects of Matrix Metalloproteinases on the Performance of Platelet Fibrin Gel Spiked With Cardiac Stem Cells in Heart Repair.
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基质金属蛋白酶对掺有心脏干细胞的血小板纤维蛋白凝胶在心脏修复中性能的影响
DOI：
10.5966/sctm.2015-0194
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发表时间：
2016-06
影响因子：
6
通讯作者：
Cheng K
中科院分区：
文献类型：
--
作者：
Shen D;Tang J;Hensley MT;Li T;Caranasos TG;Zhang T;Zhang J;Cheng K
干细胞和生物材料已被研究用于治疗性心脏修复。以前的研究表明，血小板纤维蛋白凝胶和心脏干细胞共同移植到心肌梗死（MI）的啮齿动物心脏时，有益的效果。我们假设基质金属蛋白酶（MMPs）在这种保护中发挥重要作用。因此，本研究旨在阐明MMP抑制对急性MI大鼠模型心肌内注射加标心脏干细胞的血小板纤维蛋白凝胶（细胞凝胶）的治疗获益的影响。在体外，广谱MMP抑制剂GM 6001破坏细胞伸展和心肌细胞收缩。在同基因大鼠心肌梗死模型中，MMP抑制减弱了内源性心血管细胞向注射生物材料中的募集，因此阻碍了新生血管生成和心肌发生。治疗后3周的超声心动图和组织学显示，金属蛋白酶抑制剂降低了细胞凝胶治疗MI的功能和结构益处。在用GM 6001处理的动物中，宿主血管生成、心肌细胞周期和MMP-2活性的降低是明显的。我们的研究结果表明，基质金属蛋白酶在血小板纤维蛋白凝胶掺入心脏干细胞治疗心肌梗死的治疗效果中起着至关重要的作用。
Stem cells and biomaterials have been studied for therapeutic cardiac repair. Previous studies have shown the beneficial effects of platelet fibrin gel and cardiac stem cells when cotransplanted into rodent hearts with myocardial infarction (MI). We hypothesized that matrix metalloproteinases (MMPs) play an important role in such protection. Thus, the present study is designed to elucidate the effects of MMP inhibition on the therapeutic benefits of intramyocardial injection of platelet fibrin gel spiked with cardiac stem cells (cell‐gel) in a rat model of acute MI. In vitro, broad‐spectrum MMP inhibitor GM6001 undermines cell spreading and cardiomyocyte contraction. In a syngeneic rat model of myocardial infarction, MMP inhibition blunted the recruitment of endogenous cardiovascular cells into the injected biomaterials, therefore hindering de novo angiogenesis and cardiomyogenesis. Echocardiography and histology 3 weeks after treatment revealed that metalloproteinase inhibition diminished the functional and structural benefits of cell‐gel in treating MI. Reduction of host angiogenesis, cardiomyocyte cycling, and MMP‐2 activities was evident in animals treated with GM6001. Our findings suggest that MMPs play a critical role in the therapeutic benefits of platelet fibrin gel spiked with cardiac stem cells for treating MI.