活体MR成像监测移植干细胞治疗SD大鼠心肌梗死并评价左心功能的可行性研究

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目的以超小超顺磁性氧化铁(USPIO)标记SD大鼠脂肪来源干细胞(ADSCs),探讨临床型1.5T MR扫描仪活体示踪SD大鼠急性心梗后心肌注射USPIO标记的干细胞并同时评估心功能的可行性。方法 USPIO40μg Fe/ml、多聚赖氨酸(poly-l-lysine,PLL)1.5μg/ml与ADSCs共孵育培养,普鲁士蓝染色和透射电镜验证标记有效性、MTS试验验证标记安全性。开胸结扎实验组(n=10)SD大鼠冠状动脉前降支建立心梗模型并于心肌内注射标记干细胞,术后利用1.5T MR扫描仪对实验组和空白对照组(n=5)大鼠行磁共振成像,观察心肌信号、计算并比较两组大鼠的左室舒张末容积(left-ventricular end-diastolic volume,LVEDV)、左室收缩末容积(left-ventricular end-systolic volume,LVESV)及左室射血分数(left-ventricular ejection fraction,LVEF)。病理组织学检查观察心肌结构和标记ADSCs的分布。结果普鲁士蓝染色显示USPIO标记ADSCs的阳性率>99%,透射电镜下可见黑色氧化铁颗粒位于细胞溶酶体内,MTS试验证实USPIO标记对ADSCs细胞活性无明显影响。开胸结扎冠脉前降支成功构建心梗模型,实验组大鼠心脏于FIESTA和FSPGR序列图像上可见左室前壁内信号降低和室壁运动异常,2D MDE序列图像上发现实验组心肌内延迟强化。实验组LVEDV、LVESV、LVEF分别为0.52±0.05ml,0.20±0.03ml和61.0±4.3%,空白对照组分别为0.44±0.04ml,0.25±0.05ml和42.7±13.4%,两组大鼠的LVEF、LVEDV差异具有统计学意义(P<0.05)。病理组织学检查于梗死心肌周边发现局灶性氧化铁颗粒沉积。结论临床1.5T MR成像仪活体示踪SD大鼠心肌梗死注射移植USPIO标记的ADSCs并同时评估SD大鼠心功能是可行的。 OBJECTIVE: To label SD rat adipose-derived stem cells (ADSCs) with ultra-small superparamagnetic iron oxide (USPIO) and investigate the clinical application of the 1.5T MR scanner in vivo. Feasibility of heart function. METHODS: USPIO 40μg Fe / ml and poly-l-lysine (PLL) 1.5μg / ml were co-cultured with ADSCs. Prussian blue staining and transmission electron microscopy were used to validate the markers. MTS test was used to verify the safety of the markers. The myocardial infarction model was established by anterior descending coronary artery in the thoracotomy group (n = 10), and the labeled stem cells were injected into the myocardium. After 1.5T MR scanner, the experimental group and the blank control group (n = 5) The left ventricular end-diastolic volume (LVEDV) and left-ventricular end-systolic volume (LVEDV) were calculated and compared between the two groups. LVESV) and left ventricular ejection fraction (LVEF). Histopathological examination of myocardial structure and distribution of labeled ADSCs. Results Prussian blue staining showed that the positive rate of USPIO-labeled ADSCs was> 99%. The TEM showed that the black iron oxide particles were localized in the lysosome. MTS assay showed that the USPIO labeling had no significant effect on the ADSCs activity. Myocardial infarction model was successfully established by thoracotomy and ligation of the anterior descending coronary artery. The signal of the anterior wall of the left ventricle and the abnormality of the wall were observed in the FIESTA and FSPGR images in the heart of the rats in the experimental group. Myocardial delay was found in the 2D MDE images strengthen. The LVEDV, LVESV and LVEF in the experimental group were 0.52 ± 0.05ml, 0.20 ± 0.03ml and 61.0 ± 4.3% respectively, while the blank control group were 0.44 ± 0.04ml, 0.25 ± 0.05ml and 42.7 ± 13.4% respectively. The LVEF , LVEDV difference was statistically significant (P <0.05). Histopathological examination revealed focal iron oxide deposition on the periphery of infarcted myocardium. Conclusion It is feasible to inject the USPIO-labeled ADSCs and assess the cardiac function of SD rats simultaneously by injecting the 1.5T MR imager in vivo into SD rats with myocardial infarction.
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