Intramyocardial Injection of Autologous Cardiospheres or Cardiosphere-Derived Cells Preserves Function and Minimizes Adverse Ventricular Remodeling in Pigs With Heart Failure Post-Myocardial Infarction
Intramyocardial Injection of Autologous Cardiospheres or Cardiosphere-Derived Cells Preserves Function and Minimizes Adverse Ventricular Remodeling in Pigs With Heart Failure Post-Myocardial Infarction
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DOI：
10.1016/j.jacc.2010.07.049
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发表时间：
2011-01-25
影响因子：
24
通讯作者：
Marban, Eduardo
中科院分区：
文献类型：
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作者：
Lee, Shuo-Tsan;White, Anthony J.;Marban, Eduardo
目的探讨心肌球衍生细胞（cardiosphere-derived cells，CDCs）及其三维前体心肌球（cardiosphere-derived cells，cardiosphere-derived cells）直接注射于小型猪心肌梗死后心力衰竭模型中用于细胞心肌成形术的安全性和有效性。方法在前间隔心肌梗死后4周，通过开胸手术将自体心肌球或心肌内膜活检生长的CDCs注射入大鼠心肌内。用琼脂糖酶标记的CDC进行的移植优化指导了细胞剂量（50万个细胞/部位）和靶组织（20个梗死周围部位）的选择。将猪随机分配至安慰剂组（n = 11）、心脏微球组（n = 8）或CDC组（n = 10）。在注射前和8周后再次采集功能数据，之后收获器官进行组织病理学检查。结果在立即围手术期之后，所有动物均存活至方案完成。射血分数在基线时相当，但在8周时，两个细胞治疗组的射血分数均高于安慰剂组（安慰剂与CDC，p = 0.01;安慰剂与心脏微球，p = 0.01）。超声心动图和血流动力学指标的疗效改善与cardiospheres不成比例;同样，cardiospheres的不良重塑比CDC更明显。诱发性电生理检测显示各组间无差异，未发现肿瘤。结论优化剂量的心脏微球或CDCs直接注射对缺血性心肌病猪心室功能保护安全有效。尽管CDC和Cardiosphere对左心室射血分数的作用相当，但Cardiosphere在改善血流动力学和局部功能以及减轻心室重构方面具有上级优势。（J Am科尔心脏病学杂志2011; 57：455-65）（C）美国心脏病学会基金会2011年
Objectives The purpose of this study was to test the safety and efficacy of direct injection of cardiosphere-derived cells (CDCs) and their 3-dimensional precursors, cardiospheres, for cellular cardiomyoplasty in a mini-pig model of heart failure after myocardial infarction.Background Intracoronary administration of CDCs has been demonstrated to reduce infarct size and improve hemodynamic indexes in the mini-pig model, but intramyocardial injection of CDCs or cardiospheres has not been assessed in large animals.Methods Autologous cardiospheres or CDCs grown from endomyocardial biopsies were injected through thoracotomy 4 weeks after anteroseptal myocardial infarction. Engraftment optimization with luciferase-labeled CDCs guided the choice of cell dose (0.5 million cells/site) and target tissue (20 peri-infarct sites). Pigs were randomly allocated to placebo (n = 11), cardiospheres (n = 8), or CDCs (n = 10). Functional data were acquired before injection and again 8 weeks later, after which organs were harvested for histopathology.Results Beyond the immediate perioperative period, all animals survived to protocol completion. Ejection fraction was equivalent at baseline, but at 8 weeks was higher than placebo in both of the cell-treated groups (placebo vs. CDC, p = 0.01; placebo vs. cardiospheres, p = 0.01). Echocardiographic and hemodynamic indexes of efficacy improved disproportionately with cardiospheres; likewise, adverse remodeling was more attenuated with cardiospheres than with CDCs. Provocative electrophysiologic testing showed no differences among groups, and no tumors were found.Conclusions Dosage-optimized direct injection of cardiospheres or CDCs is safe and effective in preserving ventricular function in porcine ischemic cardiomyopathy. Although CDCs and cardiospheres have equivalent effects on left ventricular ejection fraction, cardiospheres are superior in improving hemodynamics and regional function, and in attenuating ventricular remodeling. (J Am Coll Cardiol 2011; 57: 455-65) (C) 2011 by the American College of Cardiology Foundation