Adult Cerebrospinal Fluid Inhibits Neurogenesis but Facilitates Gliogenesis From Fetal Rat Neural Stem Cells
Adult Cerebrospinal Fluid Inhibits Neurogenesis but Facilitates Gliogenesis From Fetal Rat Neural Stem Cells
复制标题
DOI：
10.1002/jnr.22150
复制
发表时间：
2009-11-01
影响因子：
4.2
通讯作者：
Sabolek, Michael
中科院分区：
文献类型：
--
作者：
Buddensiek, Judith;Dressel, Alexander;Sabolek, Michael
神经干细胞（NSC）是神经系统疾病的细胞替代疗法的有希望的来源。将神经干细胞注入脑脊液（CSF）提供了一种非创伤性脑内移植方法。然而，移植物的细胞存活和实质内迁移是有限的。此外，最近报道CSF是控制脑中干细胞过程的重要环境。我们研究了成人软脑膜CSF对胎鼠神经干细胞行为的影响。在干细胞维持和分化期间，与标准培养基相比，CSF增加了NSC的存活。CSF的存在增强了NSC的分化，导致自我更新能力的更快丧失以及更快和更强的神经突生长。其中一些作用（主要是细胞存活、神经突分支）可通过加入骨形态发生蛋白（BMP）抑制剂头蛋白来阻断。在CSF中分化后，与标准培养基相比，发现MAP 2ab（+）神经元显著减少，但GFAP（+）星形胶质细胞增多。通过RT-PCR分析，与标准培养基相比，我们确定了NSC标记基因Nestin的mRNA在CSF中分化至72小时期间减少，但GFAP mRNA在CSF中分化至72小时期间增加。我们的数据表明，成人软脑膜CSF增强细胞存活的胚胎大鼠神经干细胞增殖和分化。此外，CSF提供神经胶质细胞生成的刺激，但抑制胎儿神经干细胞的神经发生。我们的数据表明，CSF中含有的因素，如骨形成蛋白调节神经干细胞的行为，我们假设，神经干细胞在CSF中的快速分化导致鞘内移植的神经干细胞的迁移能力的快速丧失。(C)2009 Wiley-Liss，Inc.
Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Administration of NSCs into the cerebrospinal fluid (CSF) offers a nontraumatic transplantation method into the brain. However, cell survival and intraparenchymal migration of the transplants are limited. Furthermore, CSF was recently reported to be an important milieu for controlling stem cell processes in the brain. We studied the effects of adult human leptomeningeal CSF on the behavior of fetal rat NSCs. CSF increased survival of NSCs compared with standard culture media during stem cell maintenance and differentiation. The presence of CSF enhanced NSC differentiation, leading to a faster loss of self-renewal capacity and faster and stronger neurite outgrowth. Some of these effects (mainly cell survival, neurite brancing) were blocked by addition of the bone morphogenic protein (BMP) inhibitor noggin. After differentiation in CSF, significantly fewer MAP2ab(+) neurons were found, but there were more GFAP(+) astroglia compared with standard media. By RT-PCR analysis, we determined a decrease of mRNA of the NSC marker gene Nestin but an increase of Gfap mRNA during differentiation up to 72 hr in CSF compared with standard media. Our data demonstrate that adult human leptomeningeal CSF enhances cell survival of fetal rat NSCs during proliferation and differentiation. Furthermore, CSF provides a stimulus for gliogenesis but inhibits neurogenesis from fetal NSCs. Our data suggest that CSF contains factors such as BMPs regulating NSC behavior, and we hypothesize that fast differentiation of NSCs in CSF leads to a rapid loss of migration capacity of intrathecally transplanted NSCs. (C) 2009 Wiley-Liss, Inc.