Gene recombinant bone marrow mesenchymal stem cells as a tumor-targeted suicide gene delivery vehicle in pulmonary metastasis therapy using non-viral transfection.

Gene recombinant bone marrow mesenchymal stem cells as a tumor-targeted suicide gene delivery vehicle in pulmonary metastasis therapy using non-viral transfection.
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基因重组骨髓间充质干细胞作为肿瘤靶向自杀基因递送载体,用于非病毒转染肺转移治疗。

DOI:
10.1016/j.nano.2013.06.003
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发表时间:
2014
期刊:
影响因子:
5.5
通讯作者:
Gao, Jian-Qing
Gao, Jian-Qing
中科院分区:
医学3区
文献类型:
--
作者:
Zhang, Tian-Yuan;Huang, Bing;Yuan, Zhong-Yue;Hu, Yu-Lan;Tabata, Yasuhiko;Gao, Jian-Qing

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抗肿瘤基因治疗的主要限制之一是缺乏将治疗基因递送到肿瘤部位的有效方法。骨髓间充质干细胞(BMSC)已被提议作为肿瘤靶向癌症基因治疗中肿瘤部位的细胞递送载体。在这里,我们研究了表达巨细胞病毒胸苷激酶的BMSCs(TK-BMSCs)联合前药更昔洛韦对肺黑色素瘤转移的治疗作用。通过非病毒基因载体成功地工程化了BMSCs。基因重组骨髓基质细胞迁移到肺区,并被发现有倾向于靶向肿瘤结节后,系统交付。体外实验结果表明,该基因工程骨髓基质细胞在更昔洛韦存在下具有明显的自杀效应,并呈剂量依赖性;在共培养实验中,该基因工程骨髓基质细胞对B16 F10肿瘤细胞具有明显的旁观者效应。体内研究证实了TK-BMSCs/更昔洛韦对转移性肿瘤模型的治疗效果。来自临床编辑本研究使用转移性黑色素瘤模型和表达巨细胞病毒-胸苷激酶的干细胞,研究了通过骨髓间充质干细胞进行基因转移在抗癌基因治疗中的可能性,证明了明确的治疗效果。
One of the main limitations of anti-tumor gene therapy is the lack of an effective way to deliver therapeutic genes to tumor sites. Bone marrow mesenchymal stem cells (BMSCs) have been proposed as cellular delivery vehicles to tumor sites in tumor-targeted cancer gene therapy. Here, we investigated the therapeutic effects of cytomegalovirus-thymidine kinase expressing BMSCs (TK-BMSCs) on pulmonary melanoma metastasis combined with prodrug ganciclovir. BMSCs were successfully engineered through a non-viral gene vector. The gene recombinant BMSCs migrated to the pulmonary area and were found to have the tendency to target tumor nodules after systemic delivery. In vitro results demonstrate that the engineered BMSCs have significant suicide effects in the presence of ganciclovir in a dose-dependent manner and can exert a sufficient bystander effect on B16F10 tumor cells in co-culture experiments. In vivo studies confirmed the therapeutic effects of TK-BMSCs/ganciclovir on the metastasis tumor model.From the Clinical EditorThis study investigates the possibility of gene transfer via bone marrow mesenchymal stem cells in anti-cancer gene therapy using a metastatic melanoma model and cytomegalovirus-thymidine kinase expressing stem cells, demonstrating clear therapeutic effects.
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