GENE AND MOLECULAR THERAPY FOR MALIGNANT BRAIN TUMORS USING NEURAL STEM CELLS DERIVED FROM EMBRIONIC STEM CELLS

以前，我们评估了前药和化疗敏感性基因治疗恶性胶质瘤的疗效。近年来，我们从胚胎干细胞来源的人神经干/祖细胞（human neural stem/progenitor cells，hNS/PCs）作为细胞来源和新的基因用于恶性胶质瘤和其他神经源性疾病的分子治疗。这种新疗法对于治疗阿尔茨海默病可能是可行的（J Med Invest 53：61-69，2006）。基于来自微阵列表达的数据，YKL-40基因已被鉴定为人类胶质母细胞瘤中最过度表达的基因之一，并且YKL-40抑制U87细胞生长，并且观察到GI期的U87细胞显著增加。近年来，我们成功地将人神经干/祖细胞（hNS/PC）作为神经系统疾病的细胞替代治疗的细胞来源，通过检测长期扩增的hNS/PC的体内外性质的变化，并通过生物发光成像和组织学分析评估hNS/PC体内长达6个月的致瘤潜力。

Previously, we evaluated the therapeutic efficacy of the prodrugs and chemosensitivity gene therapies for malignant gliomas. Recently we have evaluated human neural stem/progenitor cells (hNS/PCs) derived from embryonic stem cell as cell sources and some new genes for molecular therapies for malignant gliomas and other neurogenic disorders.Firstly, we investigated the ability of neural stem/progenitor cells on dementia in the mouse model of nucleus basalis of Meynert lesion. This new therapy may be feasible for the treatment of Alzheimer's disease (J Med Invest 53 : 61-69, 2006).Secondly, we examined the YKL-40 gene in human glioblastomas. Based on data from the microarray expression, the YKL-40 gene has been identified as one of the most over-expressed genes in human glioblastomas and the YKL-40 inhibited U87 cell growth, and a significant increase of U87 cells in the GI phase was observed. The gene therapy using the YKL-40 may be feasible for the treatment of malignant gliomas.Recently, we have successfully evaluated human neural stem/progenitor cells (hNS/PCs) as cell sources for cell replacement therapies for neurological disorders, by examining the alteration of in vitro and in vivo property of long-term expanded hNS/PCs, and by evaluating tumorigenic potentials of hNS/PCs in vivo for up to 6 months by bioluminescent imaging and histological analysis.