Use of genetically engineered bone marrow-derived mesenchymal stem cells for glioma gene therapy
Use of genetically engineered bone marrow-derived mesenchymal stem cells for glioma gene therapy
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DOI：
10.3892/ijo_00000443
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发表时间：
2009-12-01
影响因子：
5.2
通讯作者：
Namba, Hiroki
中科院分区：
文献类型：
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作者：
Amano, Shinji;Li, Shaoyi;Namba, Hiroki
在我们以前的研究中，我们成功地治疗了一个建立C6脑肿瘤使用神经干细胞转导单纯疱疹病毒胸苷激酶基因（HSVtk）和更昔洛韦在大鼠。在本研究中，我们研究了使用从成年大鼠获得并转导HSVtk（MSCtk细胞）的间充质干细胞（MSC）代替神经干细胞，因为MSC更容易从成年受试者获得。将这些细胞与C6大鼠胶质瘤细胞进行体外共培养研究和体内共植入研究，以检查旁观者杀瘤效应，其显示足够的旁观者效应，并且仅需要1/32的MSCtk细胞即可完全根除肿瘤。还使用培养显微镜以实时方式观察体外旁观者效应，并且显示仅与MSCtk细胞接触的肿瘤细胞死亡。对已建立的C6脑肿瘤的体内治疗研究表明，肿瘤内注射MSCtk细胞，然后全身给予更昔洛韦，肿瘤大小显著减小，生存期显著延长。MSCtk和更昔洛韦联合治疗策略（MSCtk疗法）比神经干细胞疗法更具有临床应用的可行性和实用性。
In our previous study, we successfully treated an established C6 brain tumor using neural stern cells transduced with the herpes simplex virus-thymidine kinase gene (HSVtk) and ganciclovir in the rat. In the present study, we investigated the use of mesenchymal stem cells (MSCs), obtained from adult rats and transduced with HSVtk (MSCtk cells), instead of neural stem cells because MSCs are much easier to obtain from the adult subjects. Those cells were used for in vitro co-culture study and in vivo co-implantation study with C6 rat glioma cells to examine bystander tumoricidal effect, which revealed a sufficient bystander effect and only 1/32 MSCtk cells were needed for complete tumor eradication. In vitro bystander effect was also observed in a real-time fashion using a culture microscope and it was shown that only tumor cells that had contact with MSCtk cells died. In vivo treatment study of an established C6 brain tumor with an intratumoral injection of MSCtk cells followed by systemic ganciclovir administration demonstrated a significant reduction of the tumor size and a significant survival prolongation. The treatment strategy using MSCtk and ganciclovir (MSCtk therapy) is more feasible and practical for clinical application than the method using neural stem cells.