Differential fate of multipotent and lineage-restricted neural precursors following transplantation into the adult CNS
Differential fate of multipotent and lineage-restricted neural precursors following transplantation into the adult CNS
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DOI：
10.1017/s1740925x04000213
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发表时间：
2004-01-01
影响因子：
--
通讯作者：
Fischer, Itzhak
中科院分区：
文献类型：
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作者：
Lepore, Angelo C.;Han, Steven S. W.;Fischer, Itzhak
从发育中的脊髓中分离和鉴定了多种前体细胞，包括多能神经上皮细胞(NEP)、尾状细胞、神经元祖细胞(NRPs)和神经胶质前体细胞(GRPs)。我们使用从表达人胎盘碱性磷酸酶基因的转基因大鼠分离的细胞，比较了多潜能NEP细胞与谱系受限的NRP和GRP的存活、分化和整合。我们的结果表明，移植的NEP细胞存活不良，移植后3d，成年大鼠的海马体、纹状体和脊髓中未见细胞，这表明大多数CNS区与胎儿CNS来源的多能细胞移植不相容。相反，在植入后3周和5周，谱系受限的前体细胞显示出选择性地沿白质束迁移，并在所有三个中枢神经系统区域都有良好的存活。移植的前体细胞表达成熟的神经元市场NeuN和MAP2，星形细胞标记GFAP，少突胶质细胞市场RIP，NG2和SOX-10，以及突触标记突触素。当这些前体被移植到损伤的脊髓中时，也观察到了类似的行为。预分化、多潜能的NEP细胞也能存活和整合，这表明谱系受限的CNS前体细胞非常适合移植到成人CNS中，并提供了一种有前景的细胞替代候选细胞。
Multiple classes of precursor cells have been isolated and characterized from the developing spinal cord including multipotent neuroepithelial (NEP) stern cells and lineage-restricted precursors for neurons (NRPs) and glia (GRPs). We have compared the survival, differentiation and integration of multipotent NEP cells with lineage-restricted NRPs and GRPs using cells isolated from transgenic rats that express the human placental alkaline phosphatase gene. Our results demonstrate that grafted NEP cells survive poorly, with no cells observed 3 days after transplant in the adult hippocampus, striatum and spinal cord, indicating that most CNS regions are not compatible with transplants of multipotent cells derived from fetal CNS. By contrast, at 3 weeks and 5 weeks post-engraftment, lineage-restricted precursors showed selective migration along white-matter tracts and robust survival in all three CNS regions. The grafted precursors expressed the mature neuronal markets NeuN and MAP2, the astrocytic marker GFAP, the oligodendrocytic markets RIP, NG2 and Sox-10, and the synaptic marker synaptophysin. Similar behavior was observed when these precursors were transplanted into the injured spinal cord. Predifferentiated, multipotent NEP cells also survive and integrate, which indicates that lineage-restricted CNS precursors are well suited for transplantation into the adult CNS and provide a promising cellular replacement candidate.