In vitro and in vivo differentiation of boundary cap neural crest stem cells into mature Schwann cells
In vitro and in vivo differentiation of boundary cap neural crest stem cells into mature Schwann cells
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DOI：
10.1016/j.expneurol.2005.12.015
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发表时间：
2006-04-01
影响因子：
5.3
通讯作者：
Ernfors, P
中科院分区：
文献类型：
--
作者：
Aquino, JB;Hjerling-Leffler, J;Ernfors, P
在胚胎发育过程中，边界帽细胞可以产生神经元和外周胶质细胞(Maro，G.S.，Vermeren，M.，Voule escu，O.，Melton，L.，Cohen，J.，Charnay，P.，Topilko，P.，2004)。神经脊边界帽细胞是三叉神经节的神经细胞和神经胶质细胞的来源。Nat Neurosci。7(9)，930-938)，最近，边界帽被证明含有多能干细胞(HJerling-Leffler，J.，Marmigere，F.，Heglind，M.，Cederberg，A.，Koltzenburg，M.，Enerback，S.，Ernfors，P.，2005)。边界帽，神经脊干细胞的来源，产生多种感觉神经元亚型。发展。132(11)、2623-2632)。干细胞产生成熟的功能性神经胶质表型的能力还没有被解决。在本研究中，我们探讨了边界神经脊干细胞(BNCSCs)在体内外分化为成熟的功能性雪旺细胞(SCs)的能力。BNCSCs在体外培养和体内移植到成年大鼠坐骨神经中均不能分化为干细胞。然而，在神经调节蛋白的存在下，在长期培养过程中，大多数bNCSCs分化为SCs。在分析了Sox2、Sox10、S100、GFAP、纤维连接蛋白和Krox20在神经胶质细胞系中的表达后，我们利用这些标记来表征bNCSCs的分化。BNCSCs的胶质发生过程与体内相似，依次采用SC前体和未成熟的雪旺细胞，然后成熟为有髓和无髓鞘的SCs。在与移植的背根节(DRG)共培养以及体内移植到切断的坐骨神经中，这些bNCSC来源的干细胞有髓轴突，表现为神经元突起的包裹和髓鞘碱性蛋白(MBP)的表达。这些结果表明，在适当的条件下，bNCSCs可以产生成熟的具有功能的干细胞，并能在再生神经中形成髓鞘轴突。(C)2005 Elsevier Inc.保留所有权利。
Boundary cap cells can generate neurons as well as peripheral glia during embryonic development (Maro, G.S., Vermeren, M., Voiculescu, O., Melton, L., Cohen, J., Charnay, P., Topilko, P., 2004. Neural crest boundary cap cells constitute a Source of neuronal and glial cells of the PNS. Nat Neurosci. 7 (9), 930-938), and, recently, the boundary cap was shown to contain multipotent stem cells (Hjerling-Leffler, J., Marmigere, F., Heglind, M., Cederberg, A., Koltzenburg, M., Enerback, S., Ernfors, P., 2005. The boundary cap, a source of neural crest stem cells generating multiple sensory neuron subtypes. Development. 132 (11), 2623-2632). The ability of stem cells to generate mature functional glial phenotypes has not been addressed. In this Study, we have explored the competence of boundary neural crest stem cells (bNCSCs) to differentiate into mature functional Schwann cells (SCs) in vitro and in vivo. bNCSCs failed to differentiate into SCs in vitro when Cultured in a defined media and in vivo when grafted into adult rat sciatic nerves. However, in the presence of neuregulins, during long-term cultures, the majority of bNCSCs differentiated into SCs. After analysis of the in vivo expression of Sox2, Sox10, S100, GFAP, fibronectin and Krox20 in the glial lineages, we used these markers to characterize differentiation of the bNCSCs. Gliogenesis of bNCSCs proceeded similar to that in vivo by sequentially adopting a SC precursor and immature Schwann cell before maturing into myelinating and non-myelinating SCs. In co-culture with explanted dorsal root ganglia (DRG) as well as in vivo in transplants to the axotomized sciatic nerve, these bNCSC-derived SCs myelinated axons as shown by ensheathing of neuronal processes and expression of myelin basic proteins (MBP). These results show that, under appropriate conditions, bNCSCs can generate mature SCs that are functional and can myelinate axons in regenerating nerves. (C) 2005 Elsevier Inc. All rights reserved.