磁标记神经干细胞在APP／PS1转基因阿尔茨海默病小鼠脑内迁移的MRI研究  

Magnetic resonance tracking of transplanted neural stem cells labeled with superparamagnetic iron oxides in APP/PS1 transgenic mice

作　　者：陈双庆[1] 蔡庆[1] 沈玉英[1] 李铭华[2] 臧风超[3] 王培军[2] 滕皋军[4] 

机构地区：[1]南京医科大学附属苏州医院放射科,苏州215001 [2]同济大学附属同济医院放射科 [3]东南大学江苏省分子影像重点实验室 [4]东南大学附属中大医院放射科

出　　处：《中华放射学杂志》2013年第3期250-254,共5页Chinese Journal of Radiology

基　　金：国家自然科学基金资助项目（81071201）

摘　　要：目的利用MRI示踪研究超顺磁性氧化铁（SPIO）标记的神经干细胞（NSCs）在APP／PS1转基因阿尔茨海默病（AD）小鼠脑内的迁移特点。方法培养、扩增C57BL／6小鼠NSCs，制备菲立磁（Feridex）和左旋多聚赖氨酸复合物对NSCs进行标记，透射电镜进行鉴定。取12月龄APP!PSI转基因AD小鼠24只，随机数字表法等分为A、B两组，分别移植磁标记NSCs（A组）和未标记NSCs（B组）至小鼠右侧海马区，相同月龄同窝出生的野生型小鼠12只作为对照组（C组），移植磁标记NSCs。移植后1、2、4及6周分别运用7．0T高场强MR扫描仪对移植的NSCs进行活体示踪，并对照组织病理学检测结果进行对照研究。结果C57BL／6小鼠NSCs培养及扩增成功，透射电镜可见标记细胞胞质内大量含铁颗粒。MRI显示移植后1周，在T，wI及T2＊WI上可见A组小鼠海马区注射点处出现类圆形低信号影，以EWI最明显；移植后2周，观察到低信号沿移植点向周围弥漫扩散，范围逐渐变大；移植后4周，低信号范围更大，几乎遍及整个海马区，但低信号强度减低；移植后6周，MRI显示低信号影基本消失。B组小鼠各时点移植区均无明显的低信号改变。C组小鼠尽管在移植磁标记NSCs后在海马区显示低信号影，但其大小和位置未出现明显的改变。普鲁士蓝染色观察到磁标记NSCs在AD小鼠海马区的迁移在各时点基本上与MR影像相对应。结论NSCs移植到APP／PS1转基因AD小鼠海马区后向周围发生弥散性、不定向迁移，利用MRI技术可以对移植后的磁标记NSCs进行活体示踪。Objective To label neural stem cells （NSCs） with superparamagnetic iron oxides （SPIO） and to explore the tropism of NSCs after transplantation into the hippocampus of APP/PS1 AD mice by MRI. Methods NSCs from C57BL/6 mouse were cultured and identified. Feridex and Poly-L-Lysine were added into the medium to be co-cultured to make magnetic labeled NSCs and transmission electron microscopy was used to identify the iron particles in NSCs. Transgenic （ tg ） and wild-type （ wt ） mice at 12 months of age were divided into three groups： SPIOs labeled NSCs group （A and C）, unlabeled NSCs group（B）. Feridex-labeled NSCs were migrated into the hippocampus of APP/PS1 AD mice to monitor in vivo by MRI. After 1,2,4 and 6 weeks, the mice were sacrificed and their brain tissues were sectioned to investigate the migration of SPIO labeled NSCs and compared with MRI. Results NSCs of C57BL/6 mice were cultured successfully. Transmission electron microscope showed visible iron granules in cytoplasm. MRI detection of labeled cells： T2WI and T2＊WI showed remarkable low signal intensity at the hippocampus injection points 1 week after transplantation, particularly on T2＊ WI. Area of low signal intensity enlarged increasingly along the injection points after 2 weeks. At 4 weeks, area of low signal intensity spreadthroughout the hippocampus, but intensity shadowed. Six weeks later, low signal intensity almost disappeared. There was no obvious low signal change in unlabeled cell transplantation group. For wt mice, size and location of low signal did not appear obvious change at all designated time points. Prussian blue positive cells were observed in the hippocampus,indicating that NSCs labeled with SPIO could survive, migrate and differentiate in the brain of the APP/PS1 AD mice. Changes of pathology were well correlated with the area where a signal intensity loss was observed in MRI 1,2,4 and 6 weeks after transplantation. Conclusions Diffuse migration of transplanted NSCs labeled with SPIO is observed in

关 键 词：阿尔茨海默病 干细胞移植 磁共振成像 

分 类 号：R749.16[医药卫生—神经病学与精神病学]