Li Shaoyi, Tokuyama Tsutomu, Yamamoto Junkoh, Koide Masayo, Yokota Naoki, Namba Hiroki
Department of Neurosurgery, Hamamatsu University School of Medicine, Handayama, Japan.
Cancer Gene Ther. 2005 Jul;12(7):600-7. doi: 10.1038/sj.cgt.7700826.
Since neural stem cells (NSCs) have the ability to migrate toward a tumor mass, genetically engineered NSCs were used for the treatment of gliomas. We first evaluated the "bystander effect" between NSCs transduced with the herpes simplex virus-thymidine kinase (HSVtk) gene (NSCtk) and C6 rat glioma cells under both in vitro and in vivo conditions. A potent bystander effect was observed in co-culture experiments of NSCtk and C6 cells. In the intracranial co-implantation experiments in athymic nude mice and Sprague-Dawley rats, the animals co-implanted with NSCtk and C6 cells and treated with ganciclovir (GCV) showed no intracranial tumors and survived more than 100 days, while those treated with physiological saline (PS) died of tumor progression. We next injected NSCtk cells into the pre-existing C6 tumor in rats and treated them with GCV or PS. The tumor volume was serially measured by magnetic resonance imaging. The tumor disappeared in six out of nine rats in the NSCtk/GCV group, while all the rats treated with PS died of tumor progression by day 21. The results indicate the feasibility of a novel gene therapy strategy for gliomas through a bystander effect generated by intratumoral injection of NSCtk cells and systemic GCV administration.
由于神经干细胞（NSCs）具有向肿瘤块迁移的能力，因此基因工程化的神经干细胞被用于治疗神经胶质瘤。我们首先在体外和体内条件下评估了用单纯疱疹病毒胸苷激酶（HSVtk）基因转导的神经干细胞（NSCtk）与C6大鼠神经胶质瘤细胞之间的“旁观者效应”。在NSCtk和C6细胞的共培养实验中观察到了强大的旁观者效应。在无胸腺裸鼠和Sprague-Dawley大鼠的颅内共植入实验中，与NSCtk和C6细胞共植入并接受更昔洛韦（GCV）治疗的动物没有出现颅内肿瘤，存活超过100天，而接受生理盐水（PS）治疗的动物则死于肿瘤进展。接下来，我们将NSCtk细胞注射到大鼠预先存在的C6肿瘤中，并用GCV或PS进行治疗。通过磁共振成像连续测量肿瘤体积。NSCtk/GCV组9只大鼠中有6只肿瘤消失，而所有接受PS治疗的大鼠在第21天时均死于肿瘤进展。结果表明，通过瘤内注射NSCtk细胞和全身给予GCV产生旁观者效应，为神经胶质瘤提供一种新型基因治疗策略是可行的。
