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Application of mesenchymal stem cells as a vehicle to deliver replication-competent adenovirus for treating malignant glioma
Authors:Hai Cui  Jin Yong-Min  Jin Wen-Biao  Han Zhe-Zhu  Cui Mei-Nv  Piao Xue-Zhe  Shen Xiong-Hu  Zhang Song-Nan  Sun Hong-Hua
Affiliation:Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, PR China.
Abstract:Although gene therapy was regarded as a promising approach for glioma treatment, its therapeutic efficacy was often disappointing because of the lack of efficient drug delivery systems. Mesenchymal stem cells(MSCs) have been reported to have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy. Therefore, in this study, we attempted to treat glioma by using MSCs as a vehicle for delivering replication-competent adenovirus. We firstly compared the infectivity of type 3, type 5, and type 35 fiber-modified adenoviruses in MSCs. We also determined suitable adenovirus titer in vitro and then used this titer to analyze the ability of MSCs to deliver replication-competent adenovirus into glioma in vivo. Our results indicated that type 35 fiber-modified adenovirus showed higher infectivity than did naked type 3 or type 5 fiber-modified adenovirus. MSCs carrying replication-competent adenovirus significantly inhibited tumor growth in vivo compared with other control groups. In conclusion, MSCs are an effective vehicle that can successfully transport replication-competent adenovirus into glioma, making it a potential therapeutic strategy for treating malignant glioma.
Keywords:Mesenchymal stem cell  replication-competent adenovirus  gene therapy  glioma
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