磁探针标记骨髓干细胞移植治疗急性心肌梗死的MRI示踪研究

MR imaging of injected magnetically labeled stem cells in myocardial infarction:experiment with pigs

目的利用磁探针标记猪骨髓单个核细胞（BM-MNC），探讨磁共振成像（MRI）示踪磁探针标记BM-MNC（MR-MNC）的可行性。方法制备猪急性心肌梗死模型，分离培养14头（实验组9头，对照组5头）小型家猪的自体BM-MNC，将MR-MNC（实验组）和BM-MNC（对照组）经冠脉途径植入模型猪梗死相关动脉，术后MRI在体示踪移植细胞并与心肌组织切片对照。结果BM-MNC的超顺磁性氧化铁标记率近100％，10头（实验组7头，对照组3头）获得MRI示踪结果，MRI示心肌梗死模型均成功。3头MR-MNC移植后T2加权像（T2·WI）序列心肌梗死周边见模糊的低信号区，增强后可见此区呈现较增强前清晰的低回声信号，其中2头分别于14、21d发现低回声区消失，另1头随诊至26d因重症感染死亡；2头离体T2·WI序列示梗死区周边一个呈点状分布的低信号区。对照组均未发现低信号区。组织学检查发现5头（MR-MNC10^6以上）普鲁士染色阳性蓝细胞分布于梗死心肌周边，与磁共振信号减低区基本一致。结论1．5TMR可在体示踪心肌梗死模型猪经冠脉途径植入的MR-MNC，但移植的MR-MNC数量不应少于10^6。

Objective To investigate the efficacy of magnetic resonance imaging （MRI） in tracking bone marrow derived mononuclear cells （BM-MNCs） labeled with superparamagnetic iron oxide （SPIO） nanoparticles. Methods BM-MNCs were isolated from the bone marrow of 14 pigs. These 14 pigs underwent occlusion of the left anterior descending coronary artery （LAD） to establish myocardial infarction （MI） models and then randomly divided into 2 groups： experimental group （ n =9） to be injected with BM- MNCs labeled with SPIO intracoronarily under X-ray fluoroscopy, and control group （ n = 5 ） , to be injected with uulabelled BM-MNCs MRI was performed with a 1.5T MR scanner to demonstrate the location of the BM-MNCs once a week. T pigs were killed when no labeled BM-MSC was detected. The hearts were taken out to undergo HE staing and Prussian blue staining. Immunohistochemistry was used to detect the desmin and myosin. Results The cell labeling efficiency was almost 100 %. Contrast-enhanced MRI demonstrated successful establishment of MI models. Effective MRI tracking findings were obtained in 8 pigs, 7 of the experimental group and 3 of the control group. In 3 pigs T2 ＊ weighted MRI showed the zone of labeled cell accumulation shows vague low-signal area around the infarction area and much better conspicuity of the zone of hypoenhancement was shown under contrast-enhanced MRI. The hypoenhancement zone disappeared 14 - 21 days after the injection of BM-MSCs. Histological analyses showed that most Prussian blue positive cells were well correlated with the area where a signal intensity loss was observed in MRI. Conclusion 1.5T MR imaging can monitor the magnetically labeled BM-MNC in vivo in myocardial infarction provided the number of injected is nor less than 10^6.