Kelly S, Bliss T M, Shah A K, Sun G H, Ma M, Foo W C, Masel J, Yenari M A, Weissman I L, Uchida N, Palmer T, Steinberg G K
Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11839-44. doi: 10.1073/pnas.0404474101. Epub 2004 Jul 27.
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 ( approximately 1.2 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 beta-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.
我们对源自中枢神经系统干细胞的人神经球的存活、迁移和分化进行了表征，这些神经球在大脑中动脉远端闭塞7天后被移植到大鼠的缺血皮层中。移植后的神经球在未受损和缺血的大脑中均能在移植后4周强劲存活。存活情况受移植物与中风病灶的距离影响，且与IB4阳性炎症细胞数量呈负相关。在缺血动物中观察到人类细胞的定向迁移，许多人类细胞主要朝着病灶远距离迁移（约1.2毫米）；在未受损的大鼠中，细胞从注射部位呈放射状迁移，数量较少且距离较短（0.2毫米）。缺血大鼠中大多数迁移细胞具有神经元表型。移植物与病灶之间的迁移细胞表达神经母细胞标志物双皮质素，而病灶边界处的人类细胞表达未成熟神经元标志物β-微管蛋白，尽管病灶边界处有一小部分细胞也表达胶质纤维酸性蛋白（GFAP）。因此，移植的源自人中枢神经系统（hCNS）的神经球在未受损和缺血的大脑中均能强劲存活，并且微环境影响它们的迁移和命运。
