磁共振成像示踪观察脑缺血大鼠脑室内移植神经干细胞的实验研究

MR tracking of transplanted labeled neural stem cells in ischemic rat ventricles

目的探讨MRI示踪观察脑缺血大鼠脑室内移植的标记神经干细胞的分布和迁移的可行性。方法选取16只雄性SD大鼠制做脑梗死模型,随机分为标记组和未标记组,每组8只,分别于脑梗死对侧侧脑室内立体定向移植超顺磁性氧化铁纳米颗粒标记和未经标记的神经干细胞。移植细胞后,不同时间点分别进行MRI连续成像观察,之后进行大鼠脑组织冷冻切片的普鲁士蓝染色。结果标记组移植后即刻的MRI即可观察到大鼠侧脑室内的移植标记细胞,移植后7天脑梗死皮质下即可见到低信号影,各对应时间点组织切片的普鲁士蓝染色与MRI结果相符。结论MRI能够在活体内连续无创的示踪观察大鼠侧脑室移植的标记神经干细胞的迁移及分布情况。

Objectives To evaluate the method of labeling neural stem cells （NSCs） with superparamagnetic iron oxide nanoparticles （SPIO） and monitor the labeled cells after transplanted into the rat ventricle with MR scanning. Methods Neural stem cells were labeled with SPIO mediated by poly-L-lysine （PLL）. Sixteen male Sprague-Dawley rats with left focal cortical infarction were divided into two groups at random. The labeled and unlabeled NSCs were transplanted into the right lateral ventricle, respectively. In vivo MR scanning was performed to track the fate of the transplanted cells. T2WI and T2 ^＊ -GRE sequences were selected. After MR imaging, two rats of each group were sacrificed and Prussian blue staining of the brain histological sections was performed to confirm the images of MRI. Results Both Prussian blue staining and electron microscopic examination of the labeled cells showed intracellular accumulation of clusters of iron oxide nanoparticles in the cytoplasm. The implanted labeled cells were visible on MR images as low signal intensity area in the injected ventricles of the receptor rats immediately. The low signal intensity was observed in the subcortical infarct lesion after 7 days. MR scanning results were confirmed by Prussian blue staining of histological sections. Conclusion NSCs labeled with SPIO nanoparticles could migrate into the lesions after transplanted into the ventricles. MR scanning is useful and noninvasive to tracking the location and distribution of the implanted cells.