Genetically engineered neural stem cells migrate and suppress glioma cell growth at distant intracranial sites
Genetically engineered neural stem cells migrate and suppress glioma cell growth at distant intracranial sites
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DOI：
10.1016/j.canlet.2006.11.024
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发表时间：
2007-06-28
期刊：
影响因子：
9.7
通讯作者：
Namba, Hiroki
中科院分区：
文献类型：
--
作者：
Li, Shaoyi;Gao, Yun;Namba, Hiroki
我们先前的研究表明，通过旁观者效应，肿瘤内注射转导有单纯疱疹病毒胸苷激酶基因(NSCtk)的神经干细胞，然后全身应用更昔洛韦(GCV)(NSCtk疗法)，成功地治疗了已建立的大鼠脑瘤。由于胶质瘤有很强的向周围脑组织侵袭的倾向，这是局部治疗失败的主要原因之一，在本研究中，我们将NSCtk细胞注射到大鼠脑肿瘤的远处部位，并评价了NSCtk向肿瘤的迁移能力和NSCtk治疗的抗肿瘤效果。将NSCtk细胞植入同侧大脑半球内侧2 mm处或C6大鼠脑胶质瘤细胞种植的对侧大脑半球镜像点。即使将NSCtk细胞移植到对侧大脑半球，也能观察到NSCtk细胞向C6细胞的主动迁移。全身应用GCV后，肿瘤远距离注射部位的NSCtk细胞通过旁观者效应显著抑制肿瘤生长，显著延长生存期。本研究结果提示NSCtk治疗在远离NSCtk注射部位的区域仍然有效，因此适用于脑内深度浸润性和广泛播散性的恶性胶质瘤的治疗。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
Our previous study demonstrated successful treatment of an established rat brain tumor through the bystander effect by intra-tumoral injection of neural stem cells transduced with herpes simplex virus-thymidine kinase gene (NSCtk) followed by systemic ganciclovir (GCV) administration (NSCtk therapy). Since glioma has a strong tendency to infiltrate into surrounding brain tissue and that is one of the main causes of local treatment failure, we, in the present study, injected NSCtk cells at distant sites of rat brain tumors and evaluated migratory potential of NSCtk toward the tumor and anti-tumor effects of the NSCtk therapy of this experimental setting. NSCtk cells were intracranially implanted either at 2 mm medial in the ipsilateral hemisphere or at the mirror point in the contralateral hemisphere to the C6 rat glioma cell implantation. Active migration of NSCtk cells toward C6 cells was observed even when NSCtk cells were implanted in the contralateral hemisphere. When GCV was systemically administered, growth of intracranial tumor was markedly inhibited and the survival was significantly prolonged through the bystander effect by NSCtk cells migrated from distant injection sites of the tumor. The results of the present study suggest that NSCtk therapy is still effective in the area far from the NSCtk injection site and, therefore, suitable for treatment of malignant gliomas that deeply infiltrate and widely disseminate in the brain. (C) 2006 Elsevier Ireland Ltd. All rights reserved.