HUMAN NEURAL STEM CELLS TARGET GENE THERAPY-BRAIN TUMORS

移植的神经干细胞（NSC）显示出在整个CNS中迁移、与宿主细胞混合以及在体内表达外源转基因的显著能力。有趣的是，NSC的这种固有的迁移特性模仿了一些脑肿瘤如神经胶质瘤的迁移模式，其特征在于侵入性单细胞迁移。我们假设，可以利用神经干细胞的迁移特性将治疗基因产物传播给这些入侵的脑肿瘤细胞。最近的研究发现，小鼠神经干细胞似乎靶向颅内胶质瘤啮齿动物模型中的肿瘤细胞。 植入的鼠神经干细胞，经遗传修饰表达报告基因，广泛分布在整个肿瘤床和迁移并置积极推进肿瘤细胞，同时继续稳定表达外源报告基因。拟议的研究将确认和表征人类神经干细胞在侵入性啮齿动物和人类胶质母细胞瘤肿瘤细胞（用绿色荧光蛋白标记）的背景下的迁移特性。脑组织学和免疫细胞化学分析将用于确定NSC迁移和转基因表达的程度。这些研究将为人类神经干细胞作为一种新的、有效的递送载体，将治疗基因和载体靶向难治性、侵袭性脑肿瘤细胞提供概念证明。拟议的商业应用：人类神经干细胞代表了一个引人注目的新技术平台，对神经系统疾病的治疗具有广泛的治疗意义。它们的移植、迁移、分化和基因表达特性可用于治疗神经退行性疾病、脑肿瘤和其他疾病。在不久的将来，干细胞治疗的临床适用性，技术可行性和商业可行性的证明预计。

Transplanted neural stem cells (NSCs) show a remarkable ability to migrate throughout the CNS, intermingle with host cells, and express foreign transgenes in vivo. Intriguingly, this inherent migratory property of NSCs emulates the migratory pattern of some brain tumors such as gliomas, characterized by invasive single cell migration. We postulate that the migratory properties of NSCs can be harnessed to disseminate therapeutic genes products to these invading brain tumor cells. Recent studies found that murine NSCs appear to target tumor cells in intracranial glioma rodent models. Implanted murine NSCs, genetically modified to express a reporter gene, distributed themselves extensively throughout the tumor bed and migrated in juxtaposition to aggressively advancing tumor cells, while continuing to stably express a foreign reporter gene. Proposed studies will confirm and characterize the migratory properties of human NSCs in the context of invasive rodent and human glioblastoma tumor cells (labeled with green fluorescence protein). Brain histological and immunocytochemical analysis will be used to determine the extent of NSC migration and transgene expression. These studies will provide proof of concept for the use of human NSCs as a novel, efficient delivery vehicle to target therapeutic genes and vectors to refractory, invasive brain tumors cells. PROPOSED COMMERCIAL APPLICATIONS: Human neural stem cells represent a compelling new technology platform with widespread therapeutic implications for the treatment of neurological diseases. Their transplantation, migration, differentiation, and gene expression properties can be exploited to treat neurodegenerative disorders, brain tumors, and other diseases. Demonstration of the clinical applicability, technical feasibility, and commercial viability of stem cell therapy is anticipated in the near future.