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

在此之前，我们评估了前药和化学敏感性基因疗法对恶性胶质瘤的治疗效果。近年来，我们对胚胎干细胞衍生的人类神经干细胞/祖细胞（hNS/PCs）作为细胞来源和一些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进行了评估。首先，我们研究了神经干/祖细胞对Meynert基底核损伤小鼠痴呆模型的作用。这种新疗法可能是治疗阿尔茨海默病的一种可行的方法（J Med Invest 53: 61-69, 2006）。其次，我们检测了YKL-40基因在人胶质母细胞瘤中的表达。微阵列表达数据显示，YKL-40基因是人胶质母细胞瘤中过表达最多的基因之一，YKL-40抑制了U87细胞的生长，U87细胞在GI期显著增加。利用YKL-40基因治疗恶性胶质瘤是可行的。最近，我们成功地评估了人类神经干细胞/祖细胞（hNS/PCs）作为神经系统疾病细胞替代疗法的细胞来源，通过检测长期扩增hNS/PCs的体外和体内特性的改变，并通过生物发光成像和组织学分析评估hNS/PCs在体内长达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.