Potent bystander effect in suicide gene therapy using neural stem cells transduced with herpes simplex virus thymidine kinase gene
Potent bystander effect in suicide gene therapy using neural stem cells transduced with herpes simplex virus thymidine kinase gene
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DOI：
10.1159/000091032
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Namba, H
中科院分区：
文献类型：
--
作者：
Li, SY;Tokuyama, T;Namba, H
目的：单纯疱疹病毒胸苷激酶（HSVtk）/更昔洛韦自杀基因治疗系统被认为是恶性胶质瘤最有前途的治疗策略之一。我们一直在使用HSVtk基因转导的神经干细胞（NSCtk），具有向肿瘤块迁移的能力，用于治疗实验性脑肿瘤。在本研究中，我们评估了在HSVtk/更昔洛韦自杀基因治疗系统中，NSCtk和C6胶质瘤细胞之间的旁观者效应介导的抗肿瘤效应的效力。研究方法：将NSCtk和C6神经胶质瘤细胞以各种比例混合（NSCtk：C6细胞比例为1：1至1：64），并在体外和体内条件下评估旁观者效应。结果：体外共培养实验显示，当NSCtk：C6比例低至1：16时，肿瘤生长完全受到抑制。在大鼠脑中的体内共植入研究显示，在NSCtk：C6比率低至1：16时没有可见的肿瘤，并且所有这些大鼠存活超过100天。结论：结果清楚地证明了NSCtk和C6细胞之间的极强的旁观者效应，并且粗略估计了治疗肿瘤所需的NSCtk细胞的最小数量。版权所有（C）2005 S. Karger AG，巴塞尔。
Objective: The herpes simplex virus thymidine kinase (HSVtk)/ganciclovir suicide gene therapy system has been considered as one of the most promising therapeutic strategies for malignant gliomas. We have been using HSVtk gene-transduced neural stem cells (NSCtk) that possess an ability to migrate toward a tumor mass for the treatment of experimental brain tumors. In the present study, we evaluated the potency of anti-tumor effect mediated by the bystander effect between NSCtk and C6 glioma cells in the HSVtk/ganciclovir suicide gene therapy system. Methods: NSCtk and C6 glioma cells were mixed at various ratios ( NSCtk: C6 cell ratios of 1: 1 to 1: 64) and the bystander effect was evaluated both under in vitro and in vivo conditions. Results: In vitro co-culture experiment showed a complete tumor growth inhibition at the NSCtk: C6 ratios as low as 1: 16. In vivo co-implantation study in the rat brain showed no visible tumors at the NSCtk: C6 ratios as low as 1: 16 and all those rats survived more than 100 days. Conclusion: The results clearly demonstrated an extremely potent bystander effect between NSCtk and C6 cells, and the minimum number of NSCtk cells needed for the treatment of tumors was roughly estimated. Copyright (C) 2005 S. Karger AG, Basel.