MagA基因修饰间充质干细胞介导的肿瘤转移灶磁共振检测及磁热疗

项目名称： MagA基因修饰间充质干细胞介导的肿瘤转移灶磁共振检测及磁热疗

项目编号： No.81201744

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 冯川

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： 恶性肿瘤转移灶的发现对病情评估至关重要，而目前对转移灶的特异性治疗也存在困难。本课题以大鼠血行肝转移模型为例。将磁共振报告基因MagA基因转染入间充质干细胞，在间充质干细胞内持续形成内生性超顺磁性氧化铁纳米颗粒（SPIONs, superparamagnetic iron oxide nanoparticles）。利用间充质干细胞对肿瘤转移灶特异性归巢的性质，将间充质干细胞内含的SPIONs特异性运送至肿瘤转移灶部位，使其在肿瘤转移灶内持续性富集。这些SPIONs降低磁共振T2*WI信号的特性，将会增强转移灶与周围组织对比度，达到增加肿瘤转移灶检出率的目的。并利用SPIONs在交变磁场下产热效应，特异性的在肿瘤转移灶内形成相对高热，致肿瘤细胞凋亡及坏死，达到特异性消除肿瘤转移灶的目的，同时也消除移植间充质干细胞的生物效应。为发现和特异性治疗恶性肿瘤转移灶提供新的方法模式及坚实的实验基础。

中文关键词： 间充质干细胞；转移瘤；磁共振；磁热疗；超顺磁性氧化铁纳米微粒

英文摘要： The detection and the targeted therapy of metastatic tumor is very important to the patient.To increase detection rate of metastatic tumors and improve targeted therapy, the mesenchymal stem cells (MSCs) which can specifically migrate to tumor is used as a gene delivery in this study. We'll make the animal metastatic tumor model in rat liver. MSCs will gain the expression of MagA gene by lentivirus and then contain the superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs would be enriched specifically in the metastatic tumors with MSCs migration after transplant. These SPIONs would enhance contrast between metastatic tumors and normal tissue by the T2*WI signal reduction. The enhanced contrast can help us to find metastatic tumors more accurately. These SPIONs in metastatic tumors can also be remotely heated upon exposure to an external alternating magnetic field.And the temperature of metastatic tumor areas will be rised specifically. The targeted magnetic hyperthermia therapy would lead to apoptosis and necrosis of cells. So the metastatic tumors and the transplant MSCs would be eliminated. The results of this study would be helpful to the detection of metastatic tumors and to the targeted therapy.

英文关键词： mesenchymal stem cells；metastatic tumors；Magnatic Resonance Imaging；Magnetic hyperthermia；Super paramagnetic iron oxide nanoparticles