Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex
Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex
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DOI：
10.1073/pnas.0404474101
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发表时间：
2004-08-10
影响因子：
11.1
通讯作者：
Steinberg, GK
中科院分区：
文献类型：
--
作者：
Kelly, S;Bliss, TM;Steinberg, GK
我们的特点的生存，迁移和分化的人神经球来源于中枢神经系统干细胞移植到缺血性皮质大鼠大脑中动脉闭塞后7天。移植的神经球在移植后4周在幼稚和缺血脑中存活。存活率受移植物与卒中病变的接近程度的影响，并且与IB 4阳性炎性细胞的数量呈负相关。在缺血性动物中观察到人细胞的靶向迁移，许多人细胞主要向病变长距离迁移（约1.2 mm）;在未处理大鼠中，细胞从注射部位放射状迁移，数量较少，距离较短（0.2 mm）。在缺血大鼠中，大多数迁移细胞具有神经元表型。移植物和病变之间的迁移细胞表达成神经细胞标记物doublecortin，而在病变边缘的人类细胞表达未成熟的神经元标记物P-微管蛋白，尽管在病变边缘的一小部分细胞也表达胶质细胞酸性蛋白（GFAP）。因此，移植的人CNS（hCNS）衍生的神经球在幼稚和缺血的大脑中稳健地存活，并且微环境影响它们的迁移和命运。
We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances (approximate to1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker P-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.