Optimized delivery system achieves enhanced endomyocardial stem cell retention.
Optimized delivery system achieves enhanced endomyocardial stem cell retention.
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DOI：
10.1161/circinterventions.112.000422
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Terzic A
中科院分区：
文献类型：
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作者：
Behfar A;Latere JP;Bartunek J;Homsy C;Daro D;Crespo-Diaz RJ;Stalboerger PG;Steenwinckel V;Seron A;Redfield MM;Terzic A
基于再生细胞的疗法与递送的干细胞的有限心肌保留相关。本研究的目的是开发一种用于增强细胞滞留的内皮素递送系统。使用与递送相关的组织变形和顺应性的一维和三维模型在计算机中模拟干细胞保留。针设计，预计是最佳的，因此设计使用镍钛诺-镍和钛合金显示形状记忆和超弹性。用人间充质干细胞测试生物相容性。用直接递送到Langendorff灌注的猪心脏中或经皮给药到梗塞猪的内膜中的种属匹配的细胞进行实验验证。通过流式细胞术和真实的时间定量聚合酶链反应方法定量细胞滞留。模型，计算最佳分布的失真校准，有利于组织的顺应性，预测75°弯曲针具有小到大的梯度侧孔将确保最高的细胞保留概况。在离体心脏中，镍钛合金弯针导管（C-Cath）设计确保了3倍优于标准针的干细胞保留。在慢性梗死的情况下，使用C-Cath经皮输送干细胞产生了37.7±7.1%的保留率，而使用传统针则达到了10.0±2.8%，对生物相容性或安全性没有影响。模型指导的镍钛诺为基础的弯针输送系统的发展与增量侧孔实现增强心肌干细胞保留。
Regenerative cell-based therapies are associated with limited myocardial retention of delivered stem cells. The objective of this study is to develop an endocardial delivery system for enhanced cell retention. Stem cell retention was simulated in silico using one and three-dimensional models of tissue distortion and compliance associated with delivery. Needle designs, predicted to be optimal, were accordingly engineered using nitinol – a nickel and titanium alloy displaying shape memory and super-elasticity. Biocompatibility was tested with human mesenchymal stem cells. Experimental validation was performed with species-matched cells directly delivered into Langendorff-perfused porcine hearts or administered percutaneously into the endocardium of infarcted pigs. Cell retention was quantified by flow cytometry and real time quantitative polymerase chain reaction methodology. Models, computing optimal distribution of distortion calibrated to favor tissue compliance, predicted that a 75°-curved needle featuring small-to-large graded side holes would ensure the highest cell retention profile. In isolated hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold superior stem cell retention compared to a standard needle. In the setting of chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a 37.7±7.1% versus 10.0±2.8% retention achieved with a traditional needle, without impact on biocompatibility or safety. Modeling guided development of a nitinol-based curved needle delivery system with incremental side holes achieved enhanced myocardial stem cell retention.