Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Int J Mol Sci. 2019 Nov 16;20(22):5759. doi: 10.3390/ijms20225759.
The regulation of transplanted cell proliferation and function is important to achieve safe cell-based therapies. We previously reported that the proliferation and function of transplanted cells, which expressed the () suicide gene, could be controlled by ganciclovir (GCV) administration. However, there are some concerns regarding the use of GCV. It is reported that the () gene, a human caspase-9-derived genetically engineered suicide gene, rapidly induces cell apoptosis in the presence of apoptosis inducers, such as AP20187. In this study, we used a combination of the gene and AP20187 to achieve rapid regulation of transplanted cell proliferation. Cells from the human mesenchymal stem cell line UE7T-13 were transfected with the gene to obtain UE7T-13/iC9 cells. AP20187 significantly reduced the number of UE7T-13/iC9 cells within 24 h in a concentration-dependent manner. This reduction was much faster than the reduction of HSVtk-expressing UE7T-13 cells induced by GCV addition. Subcutaneous AP20187 administration rapidly reduced the luminescence signal from NanoLuc luciferase (Nluc)-expressing UE7T-13/iC9 cells transplanted into mice. These results indicate that the combined use of the gene and AP20187 is effective in rapidly regulating transplanted cell proliferation.
移植细胞的增殖和功能的调节对于实现安全的基于细胞的治疗方法非常重要。我们之前报道过，表达（）自杀基因的移植细胞的增殖和功能可以通过更昔洛韦（GCV）的给药来控制。然而，GCV 的使用存在一些担忧。据报道，（）基因，一种源自人 Caspase-9 的基因工程自杀基因，在存在凋亡诱导剂（如 AP20187）的情况下，能够迅速诱导细胞凋亡。在这项研究中，我们使用（）基因和 AP20187 的组合来实现对移植细胞增殖的快速调节。将人类间充质干细胞系 UE7T-13 的细胞转染（）基因，以获得 UE7T-13/iC9 细胞。AP20187 以浓度依赖性的方式在 24 小时内显著减少 UE7T-13/iC9 细胞的数量。这种减少比添加 GCV 诱导 HSVtk 表达的 UE7T-13 细胞减少的速度要快得多。皮下给予 AP20187 可迅速降低移植到小鼠体内表达 NanoLuc 荧光素酶（Nluc）的 UE7T-13/iC9 细胞的发光信号。这些结果表明，（）基因和 AP20187 的联合使用可有效快速调节移植细胞的增殖。
