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

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。

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.