Sakaguchi D S, Van Hoffelen S J, Young M J
Department of Zoology and Genetics, Iowa State University, Ames, Iowa 50011, USA.
Ann N Y Acad Sci. 2003 May;995:127-39. doi: 10.1111/j.1749-6632.2003.tb03216.x.
Transplantation of neural stem/progenitor cells has been proposed as a novel approach for the replacement and repair of damaged CNS tissues. We have evaluated the influence of the host cellular microenvironment upon the survival, differentiation, and integration of neural progenitor cells transplanted into the CNS. Using this approach, we have investigated the fate of neural progenitor cells in vivo following transplantation into the developing mammalian eye. Murine brain progenitor cells (mBPCs) isolated from neonatal mice expressing the green fluorescent protein (GFP) transgene were transplanted into the eyes of Brazilian opossums (Monodelphis domestica). Monodelphis pups are born in an extremely immature, fetal-like state. The eyes of neonatal pups provide a fetal-like environment in which to study cellular interactions between host tissues and transplanted neural progenitor cells. mBPCs were transplanted by intraocular injection in hosts ranging in age from 5 days postnatal to adult. The transplanted cells were easily identified because of their GFP fluorescence. Extensive survival, differentiation, and morphological integration of mBPCs within the host tissue was observed. We found that the younger retinas provided a more supportive environment for the morphological integration of the transplanted mBPCs. Cells with morphologies characteristic of specific retinal cell types were observed. Moreover, some transplanted mBPCs were labeled with antibodies characteristic of specific neural/retinal phenotypes. These results suggest that the host environment strongly influences progenitor cell differentiation and that transplantation of neural progenitor cells may be a useful approach aimed at treating degeneration and pathology of the CNS.
神经干细胞/祖细胞移植已被提出作为一种替换和修复受损中枢神经系统组织的新方法。我们评估了宿主细胞微环境对移植到中枢神经系统中的神经祖细胞的存活、分化和整合的影响。利用这种方法，我们研究了神经祖细胞在移植到发育中的哺乳动物眼睛后在体内的命运。从表达绿色荧光蛋白（GFP）转基因的新生小鼠中分离出的小鼠脑祖细胞（mBPCs）被移植到巴西负鼠（Monodelphis domestica）的眼睛中。负鼠幼崽出生时处于极其不成熟的、类似胎儿的状态。新生幼崽的眼睛提供了一个类似胎儿的环境，用于研究宿主组织与移植的神经祖细胞之间的细胞相互作用。通过眼内注射将mBPCs移植到出生后5天至成年的宿主中。由于其GFP荧光，移植的细胞很容易被识别。观察到mBPCs在宿主组织内广泛存活、分化和形态整合。我们发现较年轻的视网膜为移植的mBPCs的形态整合提供了更有利的环境。观察到具有特定视网膜细胞类型形态特征的细胞。此外，一些移植的mBPCs被特定神经/视网膜表型特征的抗体标记。这些结果表明宿主环境强烈影响祖细胞的分化，并且神经祖细胞移植可能是一种治疗中枢神经系统退化和病变的有用方法。
