活体成像观察骨髓间充质干细胞向胶质瘤的趋化  

Observation of bone marrow-derived mesenchymal stem cells targeting glioma with in vivo bioluminescence imaging

作　　者：杨丽平[1] 赵敬湘[2] 王蕴芳[2] 南雪[2] 李露斯[1] 袁红峰[2] 白慈贤[2] 裴雪涛[2] 

机构地区：[1]军事医学科学院输血研究所干细胞与再生医学研究室,北京100850 [2]第三军医大学西南医院神经内科,重庆400038

出　　处：《中华神经医学杂志》2010年第6期544-548,共5页Chinese Journal of Neuromedicine

基　　金：国家重点基础研究发展规划（973）项目（2005CB522702）;国家高技术＂863＂计划领域重大专项（2006AA2A107）

摘　　要：目的 观察大鼠BMSCs在颅内的分布及向肿瘤的趋化能力.方法 分离、纯化、培养大鼠BMSCs,检测其表面抗原,并构建稳定表达海肾荧光素酶（RL）的BMSCs（BMSCsRL）;采用立体定向手术,在Fischer大鼠脑实质接种PKH26标记的9L胶质瘤细胞：接种胶质瘤细胞后7d应用立体定向仪于胶质瘤对侧脑实质接种BMSCsRL.通过Xenogen活体动物体内成像系统监测BMSCsRL在颅内的分布情况,同时通过Transwell板观察体外BMSCs向肿瘤迁移的情况.结果从大鼠骨髓分离的BMSCs的CD90和CD44阳性率为99%;BMSCs有向肿瘤组织趋化的能力,体外实验发现迁移的细胞数量随9L细胞的增多而增多,在体实验中通过生物发光成像技术观察到在接种后0,7,14 d BMSCs向肿瘤组织迁移,且在肿瘤与正常脑组织交界处最为明显.结论 BMSCs对胶质瘤有明显趋化性,能从远处向胶质瘤组织迁移并定位于其中,提示BMSCs可作为一种潜在的细胞载体用于神经胶质瘤的靶向治疗.Objective To explore the intracranial distribution of bone marrow-derived mesenchymal stem cells （BMSCs） and the ability of BMSCs shifting to glioma tissue.Methods We isolated BMSCs from the rats and constructed a BMSCsRL model that can stably express Renilla luciferase （RL）.And 9L glioma cells marked with PKH26 were implanted into the brain parenchyma of Fischer rat using stereotactic surgery;7 d after that, the BMSCsRL was implanted into the contralateral brain parenchyma.The intracranial distribution of BMSCsRL was detected by using Xenogen bioluminescance imaging （BLI）;at the same time,the migration of BMSCsRL into the glioma tissue was observed using Transwell plates.Results Phenotypical properties of the isolated BMSCs were CD90 and CD44 positive.BMSCs could be targeted to glioma tissue.In vivo BLI showed that the BMSCs shifted to the glioma tissue 0,7 and 14 d after transplantation and the junction area between tumor tissue and normal tissue was much more obvious than the other areas.Conclusion These results confirm the migratory capability of BMSCs over considerable distances, suggesting that BMSCs can be used as a delivery vehicle for targeted therapy of glioma.

关 键 词：神经胶质瘤 间充质干细胞 趋化作用 活体监测 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学] R739.41[医药卫生—基础医学]