Magnetic enhancement of cell retention, engraftment, and functional benefit after intracoronary delivery of cardiac-derived stem cells in a rat model of ischemia/reperfusion.
Magnetic enhancement of cell retention, engraftment, and functional benefit after intracoronary delivery of cardiac-derived stem cells in a rat model of ischemia/reperfusion.
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DOI：
10.3727/096368911x627381
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发表时间：
2012
影响因子：
3.3
通讯作者：
Marbán E
中科院分区：
文献类型：
--
作者：
Cheng K;Malliaras K;Li TS;Sun B;Houde C;Galang G;Smith J;Matsushita N;Marbán E
干细胞移植的效率受到低细胞保留的限制。冠状动脉内（IC）递送方便且广泛使用，但表现出特别低的细胞保留率。我们试图通过磁性靶向来改善IC细胞保留。将标记有铁微球的大鼠心肌细胞注射到同系大鼠的左心室腔中。当输注1、3或5 × 105个细胞时，在细胞注射期间和之后将1.3特斯拉磁体放置在心脏上方约1 cm处，24 h时细胞保留增加了5.2-6.4倍，而血清肌钙蛋白I（sTnI）水平没有升高。由于微血管阻塞，较高的细胞剂量（1或2 × 106个细胞）确实升高了sTnI水平;在此范围内，磁增强并没有改善细胞保留。为了评估疗效，在左前冠状动脉缺血45分钟/再灌注20分钟后，将5 × 105个铁标记的GFP表达细胞输注到大鼠心脏中，有和没有叠加磁体。通过定量PCR和光学成像，磁靶向增加了移植细胞在24小时的心脏滞留，并减少了向肺的迁移。在磁靶向组中，增强的细胞植入持续至少3周，此时左心室重构减弱，治疗益处（射血分数）更高。组织学显示，在磁性靶向组的心脏中，GFP+心肌细胞、Ki 67+心肌细胞和GFP−/ckit+细胞较多，TUNEL+细胞较少。在大鼠缺血/再灌注损伤模型中，磁增强冠状动脉内细胞递送是安全的，并改善了细胞治疗结果。
The efficiency of stem cell transplantation is limited by low cell retention. Intracoronary (IC) delivery is convenient and widely used but exhibits particularly low cell retention rates. We sought to improve IC cell retention by magnetic targeting. Rat cardiosphere-derived cells labeled with iron microspheres were injected into the left ventricular cavity of syngeneic rats during brief aortic clamping. Placement of a 1.3 Tesla magnet ~1 cm above the heart during and after cell injection enhanced cell retention at 24 h by 5.2–6.4-fold when 1, 3, or 5 × 105 cells were infused, without elevation of serum troponin I (sTnI) levels. Higher cell doses (1 or 2 × 106 cells) did raise sTnI levels, due to microvascular obstruction; in this range, magnetic enhancement did not improve cell retention. To assess efficacy, 5 × 105 iron-labeled, GFP-expressing cells were infused into rat hearts after 45 min ischemia/20 min reperfusion of the left anterior coronary artery, with and without a superimposed magnet. By quantitative PCR and optical imaging, magnetic targeting increased cardiac retention of transplanted cells at 24 h, and decreased migration into the lungs. The enhanced cell engraftment persisted for at least 3 weeks, at which time left ventricular remodeling was attenuated, and therapeutic benefit (ejection fraction) was higher, in the magnetic targeting group. Histology revealed more GFP+ cardiomyocytes, Ki67+ cardiomyocytes and GFP−/ckit+ cells, and fewer TUNEL+ cells, in hearts from the magnetic targeting group. In a rat model of ischemia/reperfusion injury, magnetically enhanced intracoronary cell delivery is safe and improves cell therapy outcomes.