Tissue-engineered, hydrogel-based endothelial progenitor cell therapy robustly revascularizes ischemic myocardium and preserves ventricular function.
Tissue-engineered, hydrogel-based endothelial progenitor cell therapy robustly revascularizes ischemic myocardium and preserves ventricular function.
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DOI：
10.1016/j.jtcvs.2014.06.038
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Woo YJ
中科院分区：
文献类型：
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作者：
Atluri P;Miller JS;Emery RJ;Hung G;Trubelja A;Cohen JE;Lloyd K;Han J;Gaffey AC;MacArthur JW;Chen CS;Woo YJ
基于细胞的血管生成治疗缺血性心力衰竭的临床效果有限，可能与非常低的细胞潴留（<1%）和弥散有关。我们开发了一种新的、组织工程的、基于水凝胶的细胞递送策略来克服这些限制，并在高细胞剂量下提供心肌内皮祖细胞（EPC）的长时间区域保留。从Wistar大鼠中分离EPCs并包封在纤维蛋白凝胶中。使用转基因eGFP+ EPCs的荧光活死染色定量体外活力。在大鼠急性心肌梗死模型（LAD结扎）中植入epc负载构建物4周。心肌内细胞注射（IC, 2×106 EPCs），空纤维蛋白和分离的LAD结扎组作为对照。采用超声心动图、多普勒血流分析和室内压力-容积分析量化血流动力学。血管发生和心室几何被量化。利用转基因eGFP+鼠的EPCs分析EPCs迁移。48小时后，EPCs在所有基质和细胞条件下的总体存活率为88.7%。移植1周后的组织学评估显示，与IC相比，转基因eGFP+ EPCs从纤维蛋白基质向梗死心肌的迁移显著（28±12.3 vs. 2.4±2.1cells/hpf, p=0.0001）。我们还观察到植入部位血管新生的显著增加。与对照组相比，epc -水凝胶治疗后心室血流动力学和几何形状有显著改善。我们提出了一种基于组织工程水凝胶的EPC介导疗法，以增强细胞递送、细胞保留、血管生成以及心肌结构和功能的保存。
Cell based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to very low cell retention (<1%) and dispersion. We developed a novel, tissue engineered, hydrogel based cell delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells (EPC) at high cell dosage. EPCs were isolated from Wistar Rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic eGFP+ EPCs. EPC-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (LAD ligation) for 4 weeks. Intramyocardial cell injection (IC, 2×106 EPCs), empty fibrin, and isolated LAD ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. EPC migration was analyzed by utilizing EPCs from transgenic eGFP+ rodents. EPCs demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-wk implants demonstrated significant migration of transgenic eGFP+ EPCs from the fibrin matrix to the infarcted myocardium as compared to IC (28±12.3 vs. 2.4±2.1cells/hpf, p=0.0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present following EPC-hydrogel therapy as compared to control. We present a tissue engineered hydrogel-based EPC mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function.