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Induction of dopaminergic neurons from human ES cells, and transplantation of the cells into monkey Parkinson's disease models

从人 ES 细胞诱导多巴胺能神经元，并将细胞移植到猴帕金森病模型中

基本信息

批准号：
17390397
负责人：
TAKAHASHI Jun
金额：
$ 10.72万
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：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

We induced dopaminergic neurons from human ES cell lines, KhES-1, -2 -3, which were established in Kyoto University, Japan-When we grafted human ES cell-derived neural progenitors into the striatum of monkey Parkinson's disease, one of the three monkeys showed tumor formation. PET scan demonstrated an increase of glucose metabolism and an uptake of fluorothimidine at the tumor region. Immunofluorescence study showed accumulation of Oct3/4-, ES cell marker positive cells in the tumor. In to analysis of the grafted cells revealed that the cells which caused tumor formation contained Oct3/4-positive ES cells, but that the cells which did not tumors contained no such cells. These results suggest that contaminated ES cells in the graft lead to tumor formation.This possibility was confirmed by using mouse ES cells. When ES cell-derived neural progenitor cells (NPCs) were selected. by fluorescence-activated cell sorting (FACS), these cells never famed any tumors in the mouse brain or subcutaneous space of immunodeficient mice.These results indicate that purification of NPCs is important for the safe and effective cell transplantation, and we are now developing the method to sort out human ES cell-derived NPCs.

我们从日本京都大学建立的人ES细胞系KhES-1、KhES-2 - 3中诱导多巴胺能神经元。当我们将人ES细胞衍生的神经祖细胞移植到患有帕金森病的猴子的纹状体中时，三只猴子中有一只显示肿瘤形成。PET扫描显示肿瘤区域葡萄糖代谢增加和氟噻嘧啶摄取增加。免疫荧光显示肿瘤内Oct 3/4-、ES细胞标志物阳性细胞聚集。对移植细胞的分析表明，引起肿瘤形成的细胞含有Oct 3/4阳性ES细胞，但不引起肿瘤的细胞不含有这种细胞。这些结果表明移植物中污染的ES细胞导致肿瘤的形成。当选择ES细胞来源的神经前体细胞（NPC）时。这些结果表明，纯化人ES细胞来源的NPCs对于安全有效的细胞移植是非常重要的，我们目前正在开发分离人ES细胞来源的NPCs的方法。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Immune or inflammatory response by the host brain suppresses neuronal differentiation of transplanted ES cell-derived neural precursor cells

DOI：
10.1002/jnr.21652
发表时间：
2008-07-01
期刊：
JOURNAL OF NEUROSCIENCE RESEARCH
影响因子：
4.2
作者：
Ideguchi, Makoto;Shinoyama, Mizuya;Takahashi, Jun
通讯作者：
Takahashi, Jun

Generation of graftable progenitors of dopaminergic neurons from mouse ES cells by a combination of co-culture and neurosphere methods.

通过共培养和神经球方法相结合，从小鼠 ES 细胞中产生多巴胺能神经元的可移植祖细胞。

DOI：
发表时间：
2006
期刊：
J Neurosci Res. 83
影响因子：
0
作者：
Morizane A;Takahashi J;Shinoyama M;Ideguchi M;Takagi Y;Fukuda H;Koyanagi M;Sasai Y;Hashimoto N.
通讯作者：
Hashimoto N.

FACS-based purification of ES cell-derived neural precursors averts tumor formation after transplantation

基于 FACS 的 ES 细胞源性神经前体纯化可避免移植后肿瘤形成