Bone marrow-derived stromal cells home to and remain in the infarcted rat heart but fail to improve function: an in vivo cine-MRI study.
Bone marrow-derived stromal cells home to and remain in the infarcted rat heart but fail to improve function: an in vivo cine-MRI study.
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DOI：
10.1152/ajpheart.00094.2008
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发表时间：
2008-08
期刊：
影响因子：
--
通讯作者：
Clarke K
中科院分区：
文献类型：
--
作者：
Carr CA;Stuckey DJ;Tatton L;Tyler DJ;Hale SJ;Sweeney D;Schneider JE;Martin-Rendon E;Radda GK;Harding SE;Watt SM;Clarke K
基础和临床研究表明，骨髓细胞治疗可以改善梗死后的心功能。在实验动物中，报告的干细胞介导的变化范围从没有可测量的改善到功能的完全恢复。然而，在临床上，左心室射血分数的平均改善约为2%至3%。基础和临床结果之间存在差异的一个可能解释是，很少有基础研究使用临床试验中用于测量心脏功能的磁共振（MR）成像（MRI）方法。因此，我们采用电影磁共振来确定骨髓基质细胞（BMSCs）对大鼠心功能的影响。培养的大鼠骨髓间充质干细胞的特征在于使用流式细胞术和标记的氧化铁颗粒和荧光标记，以允许在体内细胞跟踪和离体细胞鉴定，分别。这两种标记都不影响体外细胞增殖或分化。将大鼠心脏梗死，并将BMSC或对照培养基注射到梗死周边（n = 34）或全身输注（n = 30）。MRI用于测量心肌梗死和细胞治疗后10周的心脏形态和功能，并确定细胞分布。体内MRI、组织学和细胞再分离证实了在整个实验中BMSC成功递送并保留在心肌内。然而，在任何时间均未观察到任何心脏功能指标的显著改善。我们的结论是，培养的骨髓间充质干细胞不是最佳的细胞群体来治疗梗死的心脏。
Basic and clinical studies have shown that bone marrow cell therapy can improve cardiac function following infarction. In experimental animals, reported stem cell-mediated changes range from no measurable improvement to the complete restoration of function. In the clinic, however, the average improvement in left ventricular ejection fraction is around 2% to 3%. A possible explanation for the discrepancy between basic and clinical results is that few basic studies have used the magnetic resonance (MR) imaging (MRI) methods that were used in clinical trials for measuring cardiac function. Consequently, we employed cine-MR to determine the effect of bone marrow stromal cells (BMSCs) on cardiac function in rats. Cultured rat BMSCs were characterized using flow cytometry and labeled with iron oxide particles and a fluorescent marker to allow in vivo cell tracking and ex vivo cell identification, respectively. Neither label affected in vitro cell proliferation or differentiation. Rat hearts were infarcted, and BMSCs or control media were injected into the infarct periphery (n = 34) or infused systemically (n = 30). MRI was used to measure cardiac morphology and function and to determine cell distribution for 10 wk after infarction and cell therapy. In vivo MRI, histology, and cell reisolation confirmed successful BMSC delivery and retention within the myocardium throughout the experiment. However, no significant improvement in any measure of cardiac function was observed at any time. We conclude that cultured BMSCs are not the optimal cell population to treat the infarcted heart.
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