Transplantation of stem cells from sympathetic ganglion into the brain Parkinson disease

将交感神经节干细胞移植到帕金森病大脑中

• 批准号: 13470298
• 负责人: ITAKURA Toru
• 金额: $ 2.43万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470298/
• 关键词: Parkinson disease; Stem cell; Sympathetic ganglion; Transplantation; Parkinson disease; transplantation; sympathetic ganglion; stem cell

Stem cell has multipotent and self renewal ability, which is ideal source of donor for transplantation. We have studied transplantation of sympathetic ganglion into the brain with Parkinson disease, showing effect on parkinsonian symptoms such as bradykinesia and muscle rigidity. In the present research project we have applied transplantation of stem cells for Parkinson disease and examined effect of transplantation on parkinsonian symptoms. We also studied clinical research of sympathetic ganglion transplantation in the brain with Parkinson patients. Neural stem cells from nestin-GFP(green fluorescence protein) mouse were transplanted into the brain of 6-OHDA injected rat(an animal model of Parkinson disease). Transplanted stem cells well survived in the host brain. They increased cell numbers and extended their axons in the host brain. Surviving cells expressed TH imnmnoreactivity in the host brain. Survival rate in this experiment were 6-10%. Rotational scores after amphetamine administration were significantly reduced (77.3% on average) in the transplanted rats. Four patients undergoing thoracic sympathetic ganglia were carefully observed for long period, showing significant reduction in the percentage of time spent in the off phase. Piece of ganglion cultured in vitro revealed TH-, VMAT- and AADC- immunoreactivity.This research project clearly demonstrated the effects of stem cell transplantation on symptoms in animal model of Parkinson disease and parkinsonian patients.

干细胞具有多能性和自我更新能力，是理想的移植供体来源。我们研究了将交感神经节移植到帕金森病患者的大脑中，显示出对运动迟缓和肌肉强直等帕金森病症状的效果。在目前的研究项目中，我们将干细胞移植应用于帕金森病的治疗，并检查了移植对帕金森病症状的效果。我们还研究了帕金森患者大脑交感神经节移植的临床研究。将巢蛋白-GFP（绿色荧光蛋白）小鼠的神经干细胞移植到注射6-OHDA的大鼠（帕金森病动物模型）的大脑中。移植的干细胞在宿主大脑中存活良好。它们增加了宿主大脑中的细胞数量并延长了轴突。存活的细胞在宿主大脑中表达 TH 免疫反应性。本实验的存活率为6-10%。移植大鼠服用安非他明后，旋转评分显着降低（平均 77.3%）。对四名接受胸交感神经节治疗的患者进行了长期仔细观察，结果显示处于关闭阶段的时间百分比显着减少。体外培养的神经节片显示出 TH-、VMAT- 和 AADC- 免疫反应性。该研究项目清楚地证明了干细胞移植对帕金森病动物模型和帕金森病患者症状的影响。

项目成果

Ooiwa Y, Yoshimura R, Nakai K, Itakura J: "Dopaminergic neuroprotection and regeneration by neurturin assessed by using behavioral biochemical and histochemical measurements in a model of progressive Parkinson's disease"Brain Research. 947. 271-283 (2002)

Ooiwa Y、Yoshimura R、Nakai K、Itakura J：“通过在进行性帕金森病模型中使用行为生化和组织化学测量来评估神经营养因子的多巴胺能神经保护和再生”大脑研究。

Itakura J, Naka D, Maeshima S: "neurosurgical operation in eloquant area in the brain"Higher Brain Function Res. 22. 175-182 (2002)

Itakura J、Naka D、Maeshima S：“大脑雄辩区的神经外科手术”高等脑功能研究。

K Sawamoto, N Nakano, K Kobayashi, N Matsushita, H Takanashi, K Kakishita, A Yamamoto, T Yoshizaki, T Terashima, F Murakami, T Itakura, H Okano: "Visualization and direct isolation, and transplantation of midbrain dopaminergic neurons expressing GFP trans

K Sawamoto、N Nakano、K Kobayashi、N Matsushita、H Takanashi、K Kakishita、A Yamamoto、T Yoshizaki、T Terashima、F Murakami、T Itakura、H Okano：“表达 GFP 的中脑多巴胺能神经元的可视化和直接分离以及移植

K Sawamoto, N Nakano, K Kakishita, Y Ogawa, A Yamamoto, M Yamaguchi, K Mori, SA Goldman, T Itakura, H Okano: "Generation of dopaminergic neurons it the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene"J Neurosci. 21. 1085

K Sawamoto、N Nakano、K Kakishita、Y Okawa、A Yamamoto、M Yamaguchi、K Mori、SA Goldman、T Itakura、H Okano：“从用巢蛋白-GFP转基因标记的中脑前体细胞中产生多巴胺能神经元

板倉 徹: "コメディカルのための脳神経外科"ブレーン出版. 180 (2003)

板仓彻：《喜剧神经外科》大脑出版 180 (2003)。