Reconstruction of disturbed brain function with neural stem cells from the investigation of the mechanism and induction to neuronal differentiation by trophic factor

从机制研究及营养因子诱导神经元分化的神经干细胞重建受损脑功能

• 批准号: 16500203
• 负责人: HIDA Hideki
• 金额: $ 2.37万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16500203/
• 关键词: embryonic stem cell; dopaminergic neuron; neuronal differentiation; neural stem cell; cell cycle; low oxygen; hupoxia inducible factor-1; pleiotrophin; 胚性幹(ES)細胞; チロシン水酸化酵素; p27^<kip1>; HIF-1α; cdk5; cytokine; LIF; wnt5a; 低酸素条件; 細胞培養濃度

We investigate 1) how to increase of the number of dopaminergic (DAergic) neurons from embryonic stem (ES) cell-derived neural stem cells (NSCs) and 2) the mechanism of DAergic differentiation, and we also carried out basic research for neural transplantation using NSCs for the recovery of disturbed brain function. Data are summarized as follows.1) DAergic differentiation from NSCs are induced by low physiological oxygen in the fetal brain (3.5% 02) or cytokine mixture (IL-113, IL-11, LIF, GDNF) which is enhanced in DA-depleted striatum. 2) Cell cycle inhibition in G 1/S phase by the pre-treatment with deferoxamine (DFO) induced neuronal differentiation relating to prolonged p27^<kiP1> elevation and activation of the neuroD signaling pathway. 3) DAergic differentiation induced by pleiotrophin (PTN), IL-1β and 3.5% oxygen is mediated by the mechanism relating to enhanced expression of HIF-1 a. 4) Investigation for the question if PTN promotes the survival of grafted cells clearly reveals that PTN treatment to donor cells promotes cell survival in the striatum after transplantation in which most grafted cells are close to cell death, resulting in better functional recovery.

我们研究了1)如何从胚胎干细胞（ES）衍生的神经干细胞（NSCs）中增加多巴胺能（DAergic）神经元的数量和2)DAergic分化的机制，并开展了利用NSCs进行神经移植以恢复脑功能紊乱的基础研究。数据汇总如下：1)胚胎脑低生理氧（3.5% - 02）或细胞因子混合物（IL-113、IL-11、LIF、GDNF）在缺da纹状体中增强，可诱导NSCs的能分化。2)去铁胺（DFO）预处理对g1 /S期细胞周期的抑制诱导神经元分化，与延长p27^<kiP1>升高和激活神经d信号通路有关。3)多营养因子（PTN）、IL-1β和3.5%氧诱导的DAergic分化与HIF-1表达增强有关。4)对PTN是否促进移植物细胞存活的研究清楚地表明，PTN处理供体细胞促进移植后纹状体细胞存活，移植物细胞大部分接近死亡，功能恢复较好。

项目成果

Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats

• DOI: 10.1016/j.neuroscience.2006.10.038
• 发表时间: 2007-02-09
• 期刊: NEUROSCIENCE
• 影响因子: 3.3
• 作者: Urakawa, S.;Hida, H.;Nishino, H.
• 通讯作者: Nishino, H.

「研究成果報告書概要(欧文)」より

摘自《研究结果报告摘要（欧洲）》

• 发表时间: 2006
• 期刊: Seibutsu Butsuri 46(1)
• 作者: Yasushi Shigeri;Keiko Shimamoto
• 通讯作者: Keiko Shimamoto

Environmental enrichment brings a beneficial effect on beam walking and enhancest migration of doublecortin-positive cells following striatal lesions in rats.

环境富集对大鼠横梁行走产生有益影响，并增强大鼠纹状体损伤后双皮质素阳性细胞的迁移。

• 发表时间: 2007
• 期刊: Neuroscience 144(3)
• 作者: Urakawa;S;Hida H.;Masuda T;Misumi S;Kim T-S;Nishino H
• 通讯作者: Nishino H

Differentiation factor for stem cells in the striatum

纹状体干细胞的分化因子

• 发表时间: 2005
• 期刊: Clinical Neuroscience 44(7)
• 作者: Hida H;Jung CG;Nishino H.
• 通讯作者: Nishino H.

Pleiotrophin promotes functional recovery after neural transplantation in rats

• DOI: 10.1097/wnr.0b013e328011398e
• 发表时间: 2007-01-22
• 期刊: NEUROREPORT
• 影响因子: 1.7
• 作者: Hida, Hideki;Masuda, Tadashi;Nishino, Hitoo
• 通讯作者: Nishino, Hitoo