BACKGROUND: Recent studies have confirmed that mesenchymal stem cells (MSCs) can be used as targeted-gene delivery vehicles for cancer gene therapy. OBJECTIVE: To investigate the therapeutic effects of herpes simplex virus thymidine kinase expressing mesenchymal stem cells (TK- MSCs) in combination with Ganciclovir (GCV) on nasopharyngeal carcinoma. METHODS: The pGL3 -EGFP-TK plasmid was constructed and transfected into Sprague-Dawley rat MSCs by Lipofectamine? 2000. Cell proliferation was determined by CCK-8 method. Tumor-homing of TK-MSCs was analyzed by Transwell inserts. BALB/C nude mice were inoculated with TK-MSCs to observe the tumorigenicity. Human nasopharyngeal carcinoma cells 5-8F were interfered with TK-MSCs/GCV to investigate the cell viability and the bystander effect. RESULTS AND CONCLUSION: TK gene was transfected into MSCs successfully. There was no significant difference in cell proliferation between TK-MSCs a nd MSCs (P > 0.05). TK-MSCs maintained their tumor-homing and had no tumorigenicity. TK-MSCs/GCV significantly inhibited the growth of 5-8F cells (P < 0.01). TK-MSCs/GCV suicide gene therapy system exhibits significant inhibitory effects on growth of 5-8F cells, suggesting that MSCs can beused as delivery vehicles for targete-gene therapy of nasopharyngeal carcinoma.%背景:研究证实,间充质干细胞能通过基因修饰成为肿瘤治疗的靶向载体.目的:观察转染胸苷激酶基因的胸苷激酶-间充质干细胞联合更昔洛韦对鼻咽癌细胞的靶向杀伤作用.方法:应用LipofectamineTM结果与结论:荧光显微镜观察及RT-PCR 检测结果提示实验成功将胸苷激酶基因转染至间充质干细胞,CCK-8 检测结果显示胸苷激酶-间充质干细胞与间充质干细胞增殖能力差异无显著性意义(P > 0.05).Transwell 小室迁移实验显示胸苷激酶-间充质干细胞具有归巢特性,裸鼠移植瘤实验显示胸苷激酶-间充质干细胞无致瘤性.CCK-8 检测检测发现胸苷激酶-间充质干细胞/更昔洛韦具有旁观者效应,可明显降低5-8F 的生存率(P < 0.01).提示胸苷激酶-间充质干细胞/更昔洛韦对鼻咽癌细胞具有靶向迁移及杀伤作用,间充质干细胞可作为治疗鼻咽癌的理想靶向转运载体.2000 将表达胸苷激酶基因的重组质粒pGL3-EGFP-胸苷激酶转染至SD大鼠间充质干细胞,观察其增殖能力.应用Transwell小室观察胸苷激酶-间充质干细胞的归巢特性;将胸苷激酶-间充质干细胞植入裸鼠,观察其致瘤性;用胸苷激酶-间充质干细胞/更昔洛韦干预人鼻咽癌细胞5-8F,观察其对细胞的杀伤作用及旁观者效应.
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