Novel stem/progenitor cells with neuronal differentiation potential reside in the leptomeningeal niche
Novel stem/progenitor cells with neuronal differentiation potential reside in the leptomeningeal niche
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DOI：
10.1111/j.1582-4934.2009.00706.x
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发表时间：
2009-09-01
影响因子：
5.3
通讯作者：
Krampera, Mauro
中科院分区：
文献类型：
--
作者：
Bifari, Francesco;Decimo, Ilaria;Krampera, Mauro
能够产生神经分化细胞的干细胞通过巢蛋白的表达被识别，并驻留在大脑的特定区域，即海马体、室下区和嗅球。对于其他大脑结构，例如有助于正确皮质发育和功能的软脑膜，迄今为止没有证据表明它们可能含有干细胞/前体细胞。在这项工作中，我们首次表明，在发育至成年期间，大鼠软脑膜中存在巢蛋白阳性细胞。新鉴定的巢蛋白阳性细胞可以在体外提取和扩增，既可以作为神经球，与室下区来源的神经干细胞高度相似，也可以作为具有干细胞特征的同质细胞群。体外扩增的干细胞群可以高效分化为具有神经元表型和形态的可兴奋细胞。一旦注射到成人大脑中，这些细胞就会存活并分化成神经元，从而表明它们的神经元分化潜力在体内也能发挥作用。总之，我们的数据提供的证据表明，具有神经元分化潜力的特定未成熟细胞群在整个生命过程中都驻留在软脑膜中。由于软脑膜覆盖整个中枢神经系统，这些发现可能对皮质发育研究和应用于神经系统疾病的再生医学具有相关意义。
Stem cells capable of generating neural differentiated cells are recognized by the expression of nestin and reside in specific regions of the brain, namely, hippocampus, subventricular zone and olfactory bulb. For other brain structures, such as leptomeninges, which contribute to the correct cortex development and functions, there is no evidence so far that they may contain stem/precursor cells. In this work, we show for the first time that nestin-positive cells are present in rat leptomeninges during development up to adulthood. The newly identified nestin-positive cells can be extracted and expanded in vitro both as neurospheres, displaying high similarity with subventricular zone-derived neural stem cells, and as homogeneous cell population with stem cell features. In vitro expanded stem cell population can differentiate with high efficiency into excitable cells with neuronal phenotype and morphology. Once injected into the adult brain, these cells survive and differentiate into neurons, thus showing that their neuronal differentiation potential is operational also in vivo. In conclusion, our data provide evidence that a specific population of immature cells endowed of neuronal differentiation potential is resident in the leptomeninges throughout the life. As leptomeninges cover the entire central nervous system, these findings could have relevant implications for studies on cortical development and for regenerative medicine applied to neurological disorders.