Department of Cardiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
Int J Cardiol. 2013 Jan 20;162(3):158-65. doi: 10.1016/j.ijcard.2011.05.077. Epub 2011 Jun 2.
This study was designed to investigate the effects of treatment with autologous mesenchymal stem cells (MSCs) by intracoronary transplantation on myocardial infarction (MI) in swine.
MSCs were transfected with a lentiviral vector carrying the gene encoding green fluorescent protein (GFP) and labeled in vitro with superparamagnetic iron oxide (SPIO). An acute MI (AMI) model was established by percutaneous balloon occlusion. Dual-labeled MSC suspensions were injected through the infarct-related coronary artery using an over-the-wire (OTW) balloon device in the experimental group (n=5), while normal saline was injected into the control (n=5). Stem cell migration and improvements of cardiac function were evaluated by magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and ultrasonic cardiogram (UCG) both before MSC transplantation and after 8 weeks. At 8weeks after transplantation, myocardial tissue was analyzed by histopathologic analyses.
Blue SPIO particles were in the cytoplasm of the MSCs. The labeling efficiency reached 100%. MRI revealed hypointensities of SPIO-labeled MSCs that were clustered in the myocardial infarct area after MSC transplantation. As time progressed, the signal gradually weakened and the area shrank. SPECT revealed that the myocardial filling defect was reduced and the amount of surviving myocardium was significantly increased at 8weeks. UCG revealed significant improvement when compared with the control at 8 weeks after transplantation. Prussian blue-positive cells were observed in the MI border zone. Fluorescence-positive cells were also observed, but the number of such cells was fewer than before.
In vivo serial tracking of SPIO-labeled MSCs can be achieved by MRI. Intracoronary transplantation of SPIO-labeled MSCs can increase cardiac function and promote myocardial viability.
本研究旨在探讨经冠状动脉内移植自体间充质干细胞（MSCs）治疗对猪心肌梗死（MI）的影响。
MSCs 被携带绿色荧光蛋白（GFP）编码基因的慢病毒载体转染，并在体外用超顺磁性氧化铁（SPIO）标记。通过经皮球囊闭塞术建立急性心肌梗死（AMI）模型。在实验组（n=5）中，通过 OTW 球囊装置将双标记 MSC 混悬液注入梗死相关冠状动脉，而在对照组（n=5）中注入生理盐水。在 MSC 移植前和 8 周后，通过磁共振成像（MRI）、单光子发射计算机断层扫描（SPECT）和超声心动图（UCG）评估干细胞迁移和心功能改善情况。在移植后 8 周，通过组织病理学分析对心肌组织进行分析。
蓝色 SPIO 颗粒位于 MSCs 的细胞质中。标记效率达到 100%。MRI 显示 SPIO 标记的 MSCs 在 MSC 移植后聚集在心肌梗死区域呈现低信号。随着时间的推移，信号逐渐减弱，面积缩小。SPECT 显示，在 8 周时，心肌填充缺陷减少，存活心肌量明显增加。与对照组相比，移植后 8 周时 UCG 显示出明显改善。在 MI 边界区观察到普鲁士蓝阳性细胞。也观察到荧光阳性细胞，但数量少于之前。
通过 MRI 可以实现 SPIO 标记的 MSCs 的体内连续追踪。冠状动脉内移植 SPIO 标记的 MSCs 可以增加心功能并促进心肌存活。
