摘要
目的探讨磁标记大鼠骨髓间充质干细胞（BMSCs）活体内移植后对大鼠肝细胞癌的趋向性迁移及其机制。方法培养大鼠BMSCs，超顺磁性氧化铁粒子标记。制备大鼠肝癌模型24只，数字表法随机分为3组：实验组（n=12）经脾植入磁标记的BMSCs；对照组A（n=6）移植未标记的BMSCs；对照组B（n=6）不作任何处理。分别于移植前及移植后1、3、7和14d行MR扫描，选用T2^＊WI序列进行移植细胞的示踪并测量肿瘤组织与正常肝组织的信号强度的比值（SI/SI^＊），结果行单因素方差分析；取肿瘤组织、瘤旁正常肝组织行普鲁士蓝染色，分析BMSCs在体内的分布并与MR对照。结果BMSCs的磁标记率为90％以上。移植后实验组T2^＊WI显示肿瘤信号强度值明显减低，移植前及移植后1、3、7和14d的SI／SI^＊值分别为3．18±0．21、1．98±0．20、2．38±0．28、2．70±0．25及3．16±0．24，差异有统计学意义（F=56．65，P〈0．05）；与移植前相比，1、3、7d肿瘤信号强度的减低有统计学意义（t值分别为1．20、0．79、0．48，P值均〈0．05）。对照组移植前后各SI／SI^＊值差异无统计学意义（P〉0．05）。免疫组织化学显示实验组肿瘤边缘及内部有大量蓝染的普鲁士蓝阳性细胞分布，标记细胞在肿瘤内的分布与MR信号改变基本一致。对照组肿瘤组织普鲁士蓝染色均为阴性结果。结论BMSCs在活体内对肝癌细胞有明显的趋向迁移特性，有望成为基因治疗肝细胞癌的载体。
Objective To label rat bone marrow mesenchymal stem cells with superparamagnetic iron oxide （SPIO） and to explore the tropism of BMSCs for hepatocellular carcinoma cells after transplantation in vivo. Methods BMSCs from bone marrow of Sprague-Dawly （SD） rats were cultured isolated and purified. Labeled BMSCs was achieved using Feridex. Twenty-four hepatocellular carcinoma models of SD rats were induced two weeks before transplantation. The models were divided into three groups in random： the labeled BMSCs and unlabeled BMSCs were transplanted respectively into the rat＇s livers of experimental group （n = 12） and control group A （n = 6） via spleens, and no transplant was done for control group B （n =6）. MR imaging was performed to monitor the transplanted cells after 1,3,7,14 d using 1.5 T MR system. Signal intensity ratio （ SI/SI^ ＊ ） between tumor and hepatic tissue on T2^ ＊ WI were measured and compared by one-factor analysis of variance. After MR imaging, Prussian blue staining was performed. MR imaging findings were compared with histological sections. Results Prussian blue staining confirmed the labeling efficiency of BMSCs was above 90%. SI/SI^＊ of experimental group before and 1,3, 7, 14 d after transplantation were 3.18 ± 0. 21,1.98 ± 0. 20,2. 38 ± 0. 28,2. 70 ± 0. 25 and 3. 16 ± 0. 24 respectively. Following transplantation of BMSCs, signal intensity decrease was found in hepatocellular carcinoma of experimental group（ F = 56. 65, P 〈 0. 05 ） and low signal change decreased gradually and disappeared at two weeks after transplantation, while no remarkable low signal change was seen in the control group by T2^＊ WI （ P 〉 0. 05 ）. A large number of Prussian blue staining positive cells were found in hepatocellular carcinoma in experimental group. Histological section with Prussian blue staining had a good correlation with the signal intensity changes on MR images at different time. Conclusion BMSCs display significant tropism to hepatocellular carcinoma and may be an ideal gene therapy vehicle against hepatocellular carcinoma.
出处
《中华放射学杂志》
CAS
CSCD
北大核心
2009年第10期1102-1106,共5页
Chinese Journal of Radiology
基金
国家自然科学基金资助项目（30670611）
关键词
间质干细胞
肝肿瘤
磁共振成像
Mesenchymal stem cells
Liver neoplasms
Magnetic resonance imaging
