磁标记神经干细胞移植治疗脑梗死大鼠MRI示踪及形态学研究

目的:利用磁共振成像(MRI)技术追踪移植的超顺磁性氧化铁标记神经干细胞(NSCs),无创、动态地监测NSCs在活体脑内的存活和迁移。方法:大鼠32只制备右侧大脑中动脉瘤局灶脑缺血/再灌注(MCAO)模型,BrdU标记NSCs,立体定向磁标记NSCs脑内移植,MRI下活体动态追踪脑内移植的磁标记NSCs,实验动物于磁标记NSCs脑内移植第1、5和14天达到观察时相点后,取脑组织做石蜡切片及HE染色。结果:24只大鼠出现明显的神经功能缺失症状。MRI追踪示:磁标记NSCs脑内移植1d后,针道和侧脑室部位有低信号物质存在;磁标记NSCs脑内移植5d后,低信号物质沿胼胝体腹侧迁移;磁标记NSCs脑内移植2周,右侧(病灶侧)侧脑室部位低信号物质向缺血区迁移,其前端已达到缺血区的边缘。脑组织病理学检测:BrdU阳性磁标记NSCs沿胼胝体腹侧向缺血/再灌注区迁移。随着脑内磁标记移植时间的推移,侧脑室区的NSCs向缺血/再灌注区迁移数量逐渐增加。结论:超顺磁性氧化铁颗粒和BrdU双标记的神经干细胞移植至脑梗死大鼠脑内后可迁移到病灶区;MRI成像能够在活体内连续示踪观察神经干细胞的迁移及分布情况。

Magnetic Resonance Tracking of Transplanted Neural Stem Cells Labeled with Superparamagnetic Iron Oxide Nanoparticles in Ischemic Rats

Objective:Magnetic resonance(MR) scanning was performed to track the labeled cells after being trans-planted into the ischemic rats,dynamically monitoring the existing and mobility of neural stem cells(NSCs) in brain.Meth-ods:Thirty-two rats were used to make middle cerebral artery occlusion(MCAO)models.BrdU was used to label NSCs.The labeled NSCs were transplanted to brain.The magnetic resonance imaging(MRI) was performed to monitor the labeled NSCs.The paraffin-embedded rat brain tissues were obtained when the labeled cells transplanted into the brain in 1,5 and 14 d,respectively and then stained by HE and immunohistochemistry.Results:Twenty-four rats had obvious symptoms of central nervous system.When the labeled cells were transplanted in 1 d,the low signal intensity could be seen in needle road and intracerebroventricular,5 d later,the low signal intensity could be seen in the corpus callosum ventral,2 weeks lat-er,the low signal intensity migrated from intracerebroventricular to ischemic area,and the front-end arrived the edge.The labeled cells by BrdU were transplanted along the corpus callosum ventral to ischemic area.The quantity of labeled NSCs by BrdU was much more with the time.Conclusion:NSCs colabeled with superparamagnetic iron oxide(SPIO) nanoparticles and BrdU could migrate into the lesions after transplanted into rat brains.MRI scanning is useful and noninvasive to track the location and distribution of the labeled NSCs.