Gene therapy of gastric cancer using LIGHT-secreting human umbilical cord blood-derived mesenchymal stem cells
Gene therapy of gastric cancer using LIGHT-secreting human umbilical cord blood-derived mesenchymal stem cells
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DOI：
10.1007/s10120-012-0166-1
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发表时间：
2013-04
期刊：
影响因子：
7.4
通讯作者：
Xin-hong Zhu;D. Su;S. Xuan;G. Ma;Z. Dai;Tongyun Liu;D. Tang;Weizheng Mao;Chenfang Dong
中科院分区：
文献类型：
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作者：
Xin-hong Zhu;D. Su;S. Xuan;G. Ma;Z. Dai;Tongyun Liu;D. Tang;Weizheng Mao;Chenfang Dong
背景间充质干细胞（MSC）具有迁移到肿瘤中的能力，因此是治疗恶性疾病的潜在载体。在本研究中，我们研究了使用脐带血间充质干细胞（UCB-MSC）作为转基因LIGHT（TNFSF14）恒定源的载体来靶向体内肿瘤细胞。方法构建携带LIGHT基因的慢病毒载体，产生滴度为2×108TU/L的病毒颗粒。将LIGHT基因包装的慢病毒转染的UCB-MSCs注射入小鼠胃癌模型14天后，采用逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附试验（ELISA）检测LIGHT mRNA和蛋白的表达水平。然后测量肿瘤的大致体积。结果与 MSC 和 NaCl 处理相比，MSC-LIGHT 处理对肿瘤生长具有很强的抑制作用 (p< 0.001)。肿瘤组织病理切片检查显示，MSC-LIGHT组肿瘤坏死面积较MSC组更大。此外，我们发现具有光的MSC能够显着诱导肿瘤细胞凋亡。带有 LIGHT 基因的 UCB-MSC 中 LIGHT mRNA 和蛋白的表达水平显着高于 UCB-MSC 中的水平 (p < 0.001)。结论这些结果表明携带 LIGHT 基因的 UCB-MSC 有潜力用作治疗胃癌的有效递送载体。
BackgroundMesenchymal stem cells (MSCs) have the ability to migrate into tumors and therefore are potential vehicles for the therapy of malignant diseases. In this study, we investigated the use of umbilical cord blood mesenchymal stem cells (UCB-MSCs) as carriers for a constant source of transgenic LIGHT (TNFSF14) to target tumor cells in vivo.MethodsLentiviral vectors carrying LIGHT genes were constructed, producing viral particles with a titer of 2 × 108TU/L. Fourteen days after UCB-MSCs transfected by LIGHT gene packaged lentivirus had been injected into mouse gastric cancer models, the expression levels of LIGHT mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Then the tumors’ approximate volumes were measured.ResultsThe treatment with MSC-LIGHT demonstrated a strong suppressive effect on tumor growth compared to treatment with MSC and NaCl (p< 0.001). Examination of pathological sections of the tumor tissues showed that the areas of tumor necrocis in the MSC-LIGHT group were larger than those in the MSC group. Moreover, we found that MSCs with LIGHT were able to significantly induce apoptosis of tumor cells. The expression levels of LIGHT mRNA and protein were significantly higher in the UCB-MSCs with the LIGHT gene than the levels in UCB-MSCs (p< 0.001).ConclusionThese results suggest that UCB-MSCs carrying the LIGHT gene have the potential to be used as effective delivery vehicles in the treatment of gastric cancers.