The amniotic fluid as a source of neural stem cells in the setting of experimental neural tube defects.

The amniotic fluid as a source of neural stem cells in the setting of experimental neural tube defects.
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在实验性神经管缺陷的情况下,羊水作为神经干细胞的来源。

DOI:
10.1089/scd.2012.0215
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发表时间:
2013
影响因子:
4
通讯作者:
D. Fauza
D. Fauza
中科院分区:
医学3区
文献类型:
--
作者:
C. Turner;J. Klein;Junmei Wang;D. Thakor;Darcy Benedict;Azra J. Ahmed;Y. Teng;D. Fauza

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我们试图确定神经干细胞(NSC)是否可以从羊水中分离神经管缺陷(NTD)的设置,作为最终自体围产期治疗的先决条件。妊娠Sprague-Dawley母鼠(n=62)分为实验组(n=42)和对照组(n=20),这取决于产前暴露于维甲酸诱导胎儿NTD。在足月前处死动物进行分析(n=685只胎仔)。来自两组的羊水样本进行表观遗传选择的神经干细胞,然后暴露于神经分化培养基。在不同时间点对代表性细胞样品进行多次形态学和表型分析。对照胎仔(n=267)无任何结构异常,而52%(217/418)的实验胎仔至少出现一种类型的NTD(即,孤立性脊柱裂,n=144;孤立性露脑畸形,n=24;或两者结合,n=49)。只有来自NTD胎儿的羊膜样品产生具有典型神经祖细胞形态和Nestin和Sox-2(NSC的主要标志物)的稳健表达的细胞。这些细胞通过显示典型的形态学变化,沿着表达β-微管蛋白III、胶质细胞酸性蛋白和/或O 4(分别为未成熟神经元、星形胶质细胞和少突胶质细胞的标志物)来响应分化培养基。这与巢蛋白和Sox-2的下调同时发生。我们的结论是,羊水可以窝藏疾病特异性干细胞,例如,神经干细胞在设置实验NTDs。羊水可能是一个实用的来源自体神经干细胞适用于新形式的治疗脊柱裂。
We sought to determine whether neural stem cells (NSCs) can be isolated from the amniotic fluid in the setting of neural tube defects (NTDs), as a prerequisite for eventual autologous perinatal therapies. Pregnant Sprague-Dawley dams (n=62) were divided into experimental (n=42) and control (n=20) groups, depending on prenatal exposure to retinoic acid for the induction of fetal NTDs. Animals were killed before term for analysis (n=685 fetuses). Amniotic fluid samples from both groups underwent epigenetic selection for NSCs, followed by exposure to neural differentiation media. Representative cell samples underwent multiple morphological and phenotypical analyses at different time points. No control fetus (n=267) had any structural abnormality, whereas at least one type of NTD developed in 52% (217/418) of the experimental fetuses (namely, isolated spina bifida, n=144; isolated exencephaly, n=24; or a combination of the two, n=49). Only amniotic samples from fetuses with a NTD yielded cells with typical neural progenitor morphology and robust expression of both Nestin and Sox-2, primary markers of NSCs. These cells responded to differentiation media by displaying typical morphological changes, along with expression of beta-tubulin III, glial fibrillary acidic protein, and/or O4, markers for immature neurons, astrocytes, and oligodendrocytes, respectively. This was concurrent with downregulation of Nestin and Sox-2. We conclude that the amniotic fluid can harbor disease-specific stem cells, for example, NSCs in the setting of experimental NTDs. The amniotic fluid may be a practical source of autologous NSCs applicable to novel forms of therapies for spina bifida.
中枢神经系统细胞移植:贮积病的新疗法?
DOI: 10.1097/00019052-199604000-00013
发表时间: 1996
影响因子: 4.8
作者:
Snyder,EY;Wolfe,JH
通讯作者: Wolfe,JH
DOI: 10.1073/pnas.0306239101
发表时间: 2004-03-02
影响因子: 11.1
作者:
Teng, YD;Choi, H;Friedlander, RM
通讯作者: Friedlander, RM