Ferritin as a reporter gene for in vivo tracking of stem cells by 1.5-T cardiac MRI in a rat model of myocardial infarction
Ferritin as a reporter gene for in vivo tracking of stem cells by 1.5-T cardiac MRI in a rat model of myocardial infarction
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DOI：
10.1152/ajpheart.00935.2010
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发表时间：
2011-06-01
影响因子：
4.8
通讯作者：
Recchia, Fabio A.
中科院分区：
文献类型：
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作者：
Campan, Manuela;Lionetti, Vincenzo;Recchia, Fabio A.
坎潘M，Lionetti V，Aquaro GD，Forini F，Matteucci M，Vannucci L，Chiuppesi F，Di Cristofano C，Faggioni M，Maioli M，Barile L，Messina E，Lombardi M，Pucci A，Pistello M，Recchia FA.铁蛋白作为报告基因在心肌梗死大鼠模型中通过1.5-T心脏MRI体内追踪干细胞。美国生理学杂志心脏循环生理学300：H2238-H2250，2011年。首次发表于2011年2月18日; doi：10.1152/ajpheart.00935.2010.-目前用于通过心脏MRI跟踪干细胞的方法受到重要限制的影响，需要新的解决方案。我们测试了人铁蛋白重链（hFTH）作为报告基因在体内跟踪干细胞的心脏MRI。用慢病毒载体转导猪心脏干/祖细胞以过表达hFTH并培养以获得心脏球（Cs）。在大鼠中诱导心肌梗死，并且，45分钟后，在边界区中对动物进行类似于200 hFTH-Cs或未转导Cs或盐水溶液的心肌内注射。通过采用临床标准的1.5特斯拉MRI扫描仪和多回波T2* 梯度回波序列，我们仅在用hFTH-Cs治疗的心脏中定位铁积累组织。梗死后1周可检测到该信号，4周后其大小无明显变化（6.33 ± 3.05 vs. 4.41 ± 4.38 mm（2））。Cs转导并不影响他们的心脏修复潜力，如左心室整体和局部功能的显着更好地保存和36%的梗死面积减少，在两组接受Cs与对照梗死相比。普鲁士蓝染色证实存在分化的，铁积累细胞含有线粒体的猪源。CS衍生的细胞显示CD 31，α-平滑肌和α-肌节肌动蛋白抗原，表明分化成内皮细胞，平滑肌和心肌谱系不受铁蛋白过表达的影响。总之，hFTH可用作MRI报告基因来跟踪跳动心脏中的分裂/分化干细胞，同时监测心脏形态功能变化。
Campan M, Lionetti V, Aquaro GD, Forini F, Matteucci M, Vannucci L, Chiuppesi F, Di Cristofano C, Faggioni M, Maioli M, Barile L, Messina E, Lombardi M, Pucci A, Pistello M, Recchia FA. Ferritin as a reporter gene for in vivo tracking of stem cells by 1.5-T cardiac MRI in a rat model of myocardial infarction. Am J Physiol Heart Circ Physiol 300: H2238-H2250, 2011. First published February 18, 2011; doi: 10.1152/ajpheart.00935.2010.-The methods currently utilized to track stem cells by cardiac MRI are affected by important limitations, and new solutions are needed. We tested human ferritin heavy chain (hFTH) as a reporter gene for in vivo tracking of stem cells by cardiac MRI. Swine cardiac stem/progenitor cells were transduced with a lentiviral vector to overexpress hFTH and cultured to obtain cardiospheres (Cs). Myocardial infarction was induced in rats, and, after 45 min, the animals were subjected to intramyocardial injection of similar to 200 hFTH-Cs or nontransduced Cs or saline solution in the border zone. By employing clinical standard 1.5-Tesla MRI scanner and a multiecho T2* gradient echo sequence, we localized iron-accumulating tissue only in hearts treated with hFTH-Cs. This signal was detectable at 1 wk after infarction, and its size did not change significantly after 4 wk (6.33 +/- 3.05 vs. 4.41 +/- 4.38 mm(2)). Cs transduction did not affect their cardioreparative potential, as indicated by the significantly better preserved left ventricular global and regional function and the 36% reduction in infarct size in both groups that received Cs compared with control infarcts. Prussian blue staining confirmed the presence of differentiated, iron-accumulating cells containing mitochondria of porcine origin. Cs-derived cells displayed CD31, alpha-smooth muscle, and alpha-sarcomeric actin antigens, indicating that the differentiation into endothelial, smooth muscle and cardiac muscle lineage was not affected by ferritin overexpression. In conclusion, hFTH can be used as a MRI reporter gene to track dividing/differentiating stem cells in the beating heart, while simultaneously monitoring cardiac morpho-functional changes.