Optimization of the host brain environment for the cell replacement therapy using ES cells

使用 ES 细胞优化细胞替代疗法的宿主大脑环境

• 批准号: 20390383
• 负责人: TAKAHASHI Jun
• 金额: $ 12.4万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390383/
• 关键词: 実験脳外科学; ES細胞; 神経分化; 細胞移植; 炎症

The final goal of this study was to optimize the host brain environment for the cell replacement therapy using ES cells. By this study, we have obtained the following results : 1) Single and local blockade of IL-6 signaling promoted neuronal differentiation of transplanted ES cell-derived neural precursor cells. 2) Systemic administration of CTLA4-Ig promoted neuronal differentiation of transplanted ES cell-derived neural precursor cells. 3) Nonhypotensive dose of Telmisartan attenuated cognitive impariment partially due to peroxisome proliferator-activated receptor-γ activation in mice with chronic cerebral hypoperfusion.These results suggest that the host brain environment plays an important role in a transplantation of ES cell-derived neural cells, and also that we need to control the inflammation in the host brain for the efficient transplantation.

这项研究的最终目标是优化宿主脑环境，以便使用ES细胞进行细胞替代治疗。通过本研究，我们获得了以下结果：1)单独或局部阻断IL-6信号可促进移植的ES细胞源性神经前体细胞向神经元分化。2)全身应用CTLA4-Ig可促进移植的ES细胞源性神经前体细胞向神经元分化。3)非降压剂量替米沙坦可部分减轻慢性脑低灌流小鼠的认知功能障碍，这部分是由于过氧化物酶体增殖物激活受体-γ的激活所致。这些结果表明，宿主脑环境在ES细胞源性神经细胞移植中起着重要的作用，同时我们也需要控制宿主脑内的炎症以实现有效的移植。

项目成果

Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impairment Partially Due to Peroxisome Proliferator-Activated-γ Activation in Mice With Chronic Cerebral Hypoperfusion.

非低血压剂量的替米沙坦可减轻慢性脑灌注不足小鼠的认知障碍，部分原因是过氧化物酶体增殖物激活-γ 激活。

• 发表时间: 2010
• 作者: Washida K;Ihara M;Nishio K;Fujita Y;Maki T;Yamada M;Takahashi J;et al.
• 通讯作者: et al.

パーキンソン病に対する幹細胞移植治療の開発研究

帕金森病干细胞移植疗法的研发

• 发表时间: 2010
• 作者: 高橋淳;五味正憲
• 通讯作者: 五味正憲

Single and local blockade of IL-6 signaling promotes neuronal differentiation of transplanted ES cell-derived neural precursor cells.

单一和局部阻断 IL-6 信号传导可促进移植的 ES 细胞衍生的神经前体细胞的神经元分化。

• 发表时间: 2011
• 期刊: J Neurosci Res (in press)
• 作者: Gomi M;Aoki T;Takagi Y;Nishimura M;Ohsugi Y;Mihara M;Nozaki K;Hashimoto N;Miyamoto S;Takahashi J.
• 通讯作者: Takahashi J.

Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impairment Partially Due to Peroxisome Proliferator-Activated Receptor-γ Activation in Mice With Chronic Cerebral Hypoperfusion

• DOI: 10.1161/strokeaha.110.583948
• 发表时间: 2010-08-01
• 期刊: STROKE
• 影响因子: 8.3
• 作者: Washida, Kazuo;Ihara, Masafumi;Takahashi, Ryosuke
• 通讯作者: Takahashi, Ryosuke

細胞移植による神経再生

通过细胞移植实现神经再生

• 发表时间: 2009
• 作者: Kinoshita;Hashimoto N;Yoshimine T;Shigematsu Y.;高橋淳
• 通讯作者: 高橋淳