A comparative study of neural and mesenchymal stem cell-based carriers for oncolytic adenovirus in a model of malignant glioma.
A comparative study of neural and mesenchymal stem cell-based carriers for oncolytic adenovirus in a model of malignant glioma.
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DOI：
10.1021/mp200161f
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发表时间：
2011-10-03
影响因子：
4.9
通讯作者：
Lesniak MS
中科院分区：
文献类型：
--
作者：
Ahmed AU;Tyler MA;Thaci B;Alexiades NG;Han Y;Ulasov IV;Lesniak MS
多形性胶质母细胞瘤是中枢神经系统的一种原发性恶性肿瘤，由于其播散性质，通常是致命的。最近的研究集中在干细胞作为一种新的平台，有针对性地提供抗癌药物到大脑的独特的肿瘤嗜性。神经干细胞（NSC）和间充质干细胞（MSC）都具有作为细胞载体的潜力，用于将胶质瘤限制性溶瘤病毒靶向递送至播散性肿瘤，这是由于它们报道的肿瘤嗜性。在这项研究中，我们评估了神经干细胞和骨髓间充质干细胞作为溶瘤腺病毒在人类胶质瘤的背景下的细胞运载工具。我们报告了两种细胞系的第一次临床前比较，并表明，虽然两种干细胞系都能够支持细胞内的治疗性腺病毒复制，但从NSC释放的病毒量比MSC高出一个对数（p < 0.001）。此外，只有在原位神经胶质瘤模型中颅内施用的负载病毒的NSC显著延长了荷瘤动物的存活（NSC的中值存活68.5天对MSC的中值存活44天，p < 0.002）。将溶瘤腺病毒加载到NSC和MSC中也导致促炎基因和抗炎基因的表达，并减少载体介导的神经炎症。我们的研究结果表明，尽管具有相当的迁移能力，神经干细胞在颅内肿瘤的背景下显示出优越的上级治疗效果。综上所述，这些发现支持神经干细胞作为抗胶质瘤溶瘤病毒治疗的有效细胞载体。
Glioblastoma multiforme is a primary malignancy of the central nervous system that is universally fatal due to its disseminated nature. Recent investigations have focused on the unique tumor-tropic properties of stem cells as a novel platform for targeted delivery of anticancer agents to the brain. Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) both have the potential to function as cell carriers for targeted delivery of a glioma restricted oncolytic virus to disseminated tumor due to their reported tumor tropism. In this study, we evaluated NSCs and MSCs as cellular delivery vehicles for an oncolytic adenovirus in the context of human glioma. We report the first preclinical comparison of the two cell lines and show that, while both stem cell lines are able to support therapeutic adenoviral replication intracellularly, the amount of virus released from NSCs was a log higher than the MSC (p < 0.001). Moreover, only virus loaded NSCs that were administered intracranially in an orthotopic glioma model significantly prolonged the survival of tumor bearing animals (median survival for NSCs 68.5 days vs 44 days for MSCs, p < 0.002). Loading oncolytic adenovirus into NSCs and MSCs also led to expression of both pro- and anti-inflammatory genes and decreased vector-mediated neuroinflammation. Our results indicate that, despite possessing a comparable migratory capacity, NSCs display superior therapeutic efficacy in the context of intracranial tumors. Taken together, these findings argue in favor of NSCs as an effective cell carrier for antiglioma oncolytic virotherapy.
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影响因子：
37.8
作者：
Li, Tao-Sheng;Kubo, Masayuki;Hamano, Kimikazu
通讯作者：
Hamano, Kimikazu
影响因子：
46.9
作者：
Ahmed, A;Thompson, J;Vile, RG
通讯作者：
Vile, RG
影响因子：
3.6
作者：
Guan, Yangtai;Jiang, Zhilong;Zhang, Guang-Xian
通讯作者：
Zhang, Guang-Xian
影响因子：
2.6
作者：
Jones, Ben J.;McTaggart, Steven J.
通讯作者：
McTaggart, Steven J.
DOI：
10.1158/1078-0432.ccr-09-1292
发表时间：
2009-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Mader EK;Maeyama Y;Lin Y;Butler GW;Russell HM;Galanis E;Russell SJ;Dietz AB;Peng KW
通讯作者：
Peng KW