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

本研究的最终目的是优化使用ES细胞的细胞替代疗法的宿主脑环境。通过本研究，我们获得了以下结果：1）单一和局部阻断IL-6信号通路促进移植ES细胞源性神经前体细胞向神经元分化。2)全身给予CTLA 4-IG可促进移植ES细胞源性神经前体细胞的神经元分化。3)非扩张剂量的替米沙坦可减轻慢性脑低灌注小鼠部分由过氧化物酶体增殖物激活受体-γ激活引起的认知障碍，提示宿主脑内环境在ES细胞源性神经细胞移植中起重要作用，同时需要控制宿主脑内的炎症反应以保证有效的移植。

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.