Mechanical Loading of Stem Cells for Improvement of Transplantation Outcome in a Model of Acute Myocardial Infarction: The Role of Loading History
Mechanical Loading of Stem Cells for Improvement of Transplantation Outcome in a Model of Acute Myocardial Infarction: The Role of Loading History
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DOI：
10.1089/ten.tea.2011.0285
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发表时间：
2012-06-01
影响因子：
4.1
通讯作者：
Huard, Johnny
中科院分区：
文献类型：
--
作者：
Cassino, Theresa R.;Drowley, Lauren;Huard, Johnny
用于组织修复的干细胞治疗是一个快速发展的领域，并且决定干细胞的生理反应的因素仍然处于紧张的调查中。在这项研究中，我们假设肌肉源性干细胞（MDSC）的机械负荷历史将显着影响MDSC移植到急性梗死心肌后的MDSC存活、宿主组织血管生成和心肌功能。通过永久性左冠状动脉结扎患有急性心肌梗死的小鼠注射非刺激（NS）或机械刺激（MS）的MDSC。机械刺激包括以10%的幅度和0.5Hz的频率等双轴拉伸细胞。与用NS MDSC处理的心脏相比，MS细胞移植的心脏在梗塞周围区域显示出改善的心脏收缩力、宿主CD31 +细胞数量增加和纤维化减少。MS MDSC在体外显示出比NS细胞更高的血管内皮生长因子表达。这些发现强调了供体MDSC的循环机械负荷预处理在优化MDSC移植用于心肌修复中的重要作用。
Stem cell therapy for tissue repair is a rapidly evolving field and the factors that dictate the physiological responsiveness of stem cells remain under intense investigation. In this study we hypothesized that the mechanical loading history of muscle-derived stem cells (MDSCs) would significantly impact MDSC survival, host tissue angiogenesis, and myocardial function after MDSC transplantation into acutely infarcted myocardium. Mice with acute myocardial infarction by permanent left coronary artery ligation were injected with either nonstimulated (NS) or mechanically stimulated (MS) MDSCs. Mechanical stimulation consisted of stretching the cells with equibiaxial stretch with a magnitude of 10% and frequency of 0.5 Hz. MS cell-transplanted hearts showed improved cardiac contractility, increased numbers of host CD31 + cells, and decreased fibrosis, in the peri-infarct region, compared to the hearts treated with NS MDSCs. MS MDSCs displayed higher vascular endothelial growth factor expression than NS cells in vitro. These findings highlight an important role for cyclic mechanical loading preconditioning of donor MDSCs in optimizing MDSC transplantation for myocardial repair.