CAJ | 학술논문

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14 d行MR扫描,选用T_2*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T_2*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14 d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、7 d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监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.
목적 탐토자표기대서골수간충질간세포(BMSCs)활체내이식후대대서간세포암적추향성천이급기궤제.방법 배양대서BMSCs,초순자성양화철입자표기.제비대서간암모형24지,수자표법수궤분위3조:실험조(n=12)경비식입자표기적BMSCs;대조조A(n=6)이식미표기적BMSCs;대조조B(n=6)불작임하처리.분별우이식전급이식후1、3、7화14 d행MR소묘,선용T_2*WI서렬진행이식세포적시종병측량종류조직여정상간조직적신호강도적비치(SI/SI*),결과행단인소방차분석;취종류조직、류방정상간조직행보로사람염색,분석BMSCs재체내적분포병여MR대조.결과 BMSCs적자표기솔위90%이상.이식후실험조T_2*WI현시종류신호강도치명현감저,이식전급이식후1、3、7화14 d적SI/SI*치분별위3.18±0.21、1.98±0.20、2.38±0.28、2.70±0.25급3.16±0.24,차이유통계학의의(F=56.65,P<0.05);여이식전상비,1、3、7 d종류신호강도적감저유통계학의의(t치분별위1.20、0.79、0.48,P치균<0.05).대조조이식전후각SI/SI*치차이무통계학의의(P>0.05).면역조직화학현시실험조종류변연급내부유대량감염적보로사람양성세포분포,표기세포재종류내적분포여MR신호개변기본일치.대조조종류조직보로사람염색균위음성결과.결론 BMSCs재활체내대간암세포유명현적추향천이특성,유망성위기인치료간세포암적재체.
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 tmnsplantation. 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 T_2 * 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 T_2 * 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.