间充质干细胞对神经胶质瘤趋化能力研究

本文探讨了间充质干细胞(MSCs)对胶质瘤组织的趋化能力及分布规律。从新生儿脐血中分离出MSCs加以培养,用流式细胞仪检测表面抗原,同时做体外诱导分化实验,证明间充质干细胞性质。立体定向接种C6大鼠胶质瘤细胞,建立胶质瘤模型。将 5 -溴脱氧尿核苷(5- BrdU)标记的人间充质干细胞借助立体定向仪打入胶质瘤模型鼠预定靶区,分为原位组、同侧半球组和同侧脑室组。数日后处死大鼠,灌注固定取脑,制成石蜡切片。以苏木素伊红 (H.E. )染色确定胶质瘤组织的范围;免疫组织化学染色显示MSCs,观察其在胶质瘤组织和周围正常脑组织中的分布规律。结果显示原位组、同侧半球组和同侧脑室组均可见MSCs在胶质瘤组织中广泛分布,而在周围正常脑组织中很少见。特别是在胶质瘤组织与正常组织交界处,这一定向分布更为明显。这一结果表明人间充质干细胞对胶质瘤组织有明显趋化性,能从远处向胶质瘤组织迁移并定位于其中,提示MSCs可作为一种潜在的细胞载体用于神经胶质瘤的靶向治疗。

MESENCHYMAL STEM CELLS(MSCs) SHOW TROPISM FOR INTRACRANIAL GLIOMAS IN ADULT RAT

We explored the tropism of mesenchymal stem cells for intracranial gliomas in adult rat. Mesenchymal stem cells, which were isolated from human umbilical cord blood were cultured in vitro. The cells were identified by FACS and induced differentiation method . Glioma model rats were made by injection of C6 glioma cells into the given area of forebrain of normal SD rats on day 0. On day 7, MSCs ,which were co-cultured with BrdU for 48-72 hours beforehand, were injected stereotactically into the tumor bed, the distant intracranial site in the same hemisphere or ipsilateral cerebral lateral ventricle. Animal models were killed on day 13-15. After the process of perfusion and fixation,the brain were coronally sectioned in 4 μm slices by a rotary microtome and stained with either Hematoxylin and Eosin to observe the extent of intracranial glioma or with immunohistochemical methods to study the distribution of MSCs in glioma tissue and the normal cerebral tissue around. The results showed that MSCs, whether they were implanted in the tumor bed, the distant site in the same hemisphere or ipsilateral cerebral lateral ventricle, could be seen extensively in the range of glioma tissue, but seldomly in the normal cerebral tissue around. This feature was evident in the junction area between tumor and normal tissue. These data indicate that MSCs can migrate through long distance to target the intracranial tumor, suggesting the adjunctive use of inherently migratory MSCs as a delivery vehicle for therapeutic genes to this refractory, invasive brain tumor.