Directed differentiation of postnatal hippocampal neural stem cells generates nuclear receptor related‑1 protein‑ and tyrosine hydroxylase‑expressing cells.
Directed differentiation of postnatal hippocampal neural stem cells generates nuclear receptor related‑1 protein‑ and tyrosine hydroxylase‑expressing cells.
复制标题
出生后海马神经干细胞定向分化产生表达核受体相关1蛋白和酪氨酸羟化酶的细胞
DOI：
10.3892/mmr.2016.5489
复制
发表时间：
2016-09
影响因子：
3.4
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Ding Y;Zhang Z;Ma J;Xia H;Wang Y;Liu Y;Ma Q;Sun T;Liu J
帕金森病是一种严重的神经退行性疾病。虽然详细的分子机制仍有待阐明，PD的主要病理特征是黑质多巴胺能（DA）神经元的丢失。使用供体干细胞替代DA神经元可能是治疗PD的关键突破。本研究观察了从出生后的小鼠分离并体外培养的海马神经干细胞（Hip-NSCs）的生长动力学，特别是表达DA神经元标志物核受体相关蛋白1（Nurr 1）和酪氨酸羟化酶（TH）的细胞的产生。结果表明，Hip-NSCs在含血清的培养基中主要分化为星形胶质细胞。而在低血清条件下，βIII微管蛋白阳性神经元数量明显增加。Nurr 1阳性细胞和TH阳性神经元的比例随着Hip-NSCs定向分化时间的增加而显著增加（P分别为0.0187和0.0254）。本研究的结果表明，Hip-NSCs可以诱导分化成表达Nurr 1和TH的神经元，已知是DA神经元命运的关键调节因子。此外，它们的表达可能是促进体外神经元成熟所必需的。这些数据表明，Hip-NSC可以作为DA神经元的来源，用于诊断为PD的患者的细胞治疗。
Parkinson's disease (PD) is a severe neurodegenerative disorder. Although the detailed underlying molecular mechanism remains to be elucidated, the major pathological feature of PD is the loss of dopaminergic (DA) neurons of the substantia nigra. The use of donor stem cells to replace DA neurons may be a key breakthrough in the treatment of PD. In the present study, the growth kinetics of hippocampal neural stem cells (Hip-NSCs) isolated from postnatal mice and cultured in vitro were observed, specifically the generation of cells expressing DA neuronal markers nuclear receptor related-1 protein (Nurr1) and tyrosine hydroxylase (TH). It was revealed that Hip-NSCs differentiated primarily into astrocytes when cultured in serum-containing medium. However, in low serum conditions, the number of βIII tubulin-positive neurons increased markedly. The proportion of Nurr1-positive cells and TH-positive neurons, significantly increased with increasing duration of directed differentiation of Hip-NSCs (P=0.0187 and 0.0254, respectively). The results of the present study reveal that Hip-NSCs may be induced to differentiate in vitro into neurons expressing Nurr1 and TH, known to be critical regulators of DA neuronal fate. Additionally, their expression may be necessary to facilitate neuronal maturation in vitro. These data suggest that Hip-NSCs may serve as a source of DA neurons for cell therapy in patients diagnosed with PD.