Characterization of a human fetal spinal cord stem cell line, NSI-566RSC, and its induction to functional motoneurons.
Characterization of a human fetal spinal cord stem cell line, NSI-566RSC, and its induction to functional motoneurons.
复制标题
DOI：
10.1002/term.223
复制
发表时间：
2010-03
影响因子：
3.3
通讯作者：
Hickman, James
中科院分区：
文献类型：
--
作者：
Guo, Xiufang;Johe, Karl;Molnar, Peter;Davis, Hedvika;Hickman, James
源自人类干细胞的特定神经元亚型，尤其是运动神经元 (MN)，为 ALS 和脊髓损伤等脊髓疾病提供了显着的治疗潜力。迄今为止，在体外，仅从胚胎干细胞（hESC）和人类胎儿皮质祖细胞中成功诱导出 MN。尽管来自脊髓的神经祖细胞可能是产生 MN 的来源，但目前还没有研究报告 MN 与脊髓祖细胞在体外成功分化。这项研究首先表征了从八周胎儿中分离出的多克隆脊髓干细胞系。然后引入一个范例，成功地从该细胞系诱导 MN，这通过使用 MN 标记物 HB9、Islet1 和 ChAT 的免疫染色得到了证明。 HB9 和 ChAT（胆碱乙酰转移酶）免疫染色的组合表明，经过此诱导方案后，约 20% 的细胞是 MN。还分析了分化培养物中其他细胞类型的存在。最后，对这些分化的 MN 的电生理特性进行了表征，以确认其功能完整性。这些 MN 中的大多数会发射重复动作电位 (AP)，这是功能成熟的指标。自发兴奋性突触后电流 (EPSC) 的记录证实了这些 MN 上突触的形成。这项研究报告了首次在体外成功地从人类脊髓干细胞中分化出 MN，为设计脊髓疾病或损伤的治疗策略时获得功能性 MN 提供了一种新方法。
Specific neuronal subtypes, especially motoneurons (MNs), derived from human stem cells provide a significant therapeutic potential for spinal cord diseases such as ALS and spinal cord injury. So far in vitro, MNs have only been successfully induced from embryonic stem cells (hESC) and human fetal cortical progenitors. Although neural progenitors from spinal cord would be a likely source for generating MNs, there has been no study reporting successful in vitro differentiation of MNs from spinal cord progenitors. This study first characterized a polyclonal spinal cord stem cell line isolated from an eight-week fetus. Then a paradigm was introduced to successfully induce MNs from this cell line, which was demonstrated by the immuostaining using the MN markers HB9, Islet1 and ChAT. The combination of HB9 and ChAT (Choline Acetyl Transferase) immunostainings indicated that ~20% of the cells were MNs after this induction protocol. The presence of other cell types in the differentiated culture was also analyzed. Finally, the electrophysiological properties of these differentiated MNs were characterized to confirm their functional integrity. The majority of these MNs fired repetitive action potentials (APs), which is an indicator of functional maturation. The recordings of spontaneous Excitatory Postsynaptic Currents (EPSCs) confirmed the formation of synapses onto these MNs. This study reports the first successful differentiation of MNs from human spinal cord stem cells in vitro, providing a novel approach for obtaining functional MNs when designing the therapeutic strategy for spinal cord diseases or injuries.
登录
查看更多内容
影响因子：
2.9
作者：
Oorschot, DE;McLennan, IS
通讯作者：
McLennan, IS
影响因子：
2.5
作者：
Gao, BX;Ziskind-Conhaim, L
通讯作者：
Ziskind-Conhaim, L
影响因子：
2.9
作者：
Das, M;Molnar, P;Hickman, JJ
通讯作者：
Hickman, JJ
影响因子：
64.5
作者：
Ericson, J;Rashbass, P;Briscoe, J
通讯作者：
Briscoe, J
影响因子：
64.8
作者：
MARTI, E;BUMCROT, DA;MCMAHON, AP
通讯作者：
MCMAHON, AP