Abstract
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 herpes simplex virus thymidine kinase (HSVtk) suicide gene, could be controlled by ganciclovir (GCV) administration. However, there are some concerns regarding the use of GCV. It is reported that the inducible caspase-9 (iC9) 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 iC9 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 iC9 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 iC9 gene and AP20187 is effective in rapidly regulating transplanted cell proliferation.
Highlights
Cell-based therapies are excellent treatment methods that involve cell transplantation into patients
UE7T-13 and UE7T-13/inducible caspase-9 (iC9) cells were almost identical in appearance (Figure 1A)
To confirm iC9 gene expression in UE7T-13/iC9 cells, mRNA expression of the iC9 gene was detected by real-time polymerase chain reaction (PCR) (Figure 1B) and was found to be high
Summary
Cell-based therapies are excellent treatment methods that involve cell transplantation into patients. The development of iPS cells or ES cells opened the possibility of mass production of various kinds of tissue-specific cells, which was one of the biggest hurdles of cell-based therapies for a long time [1,2,3,4,5,6]. Some attempts have been made to solve this risk [15,16,17], but none have been completely effective Another concern is the regulation of transplanted cell function. In this study, we attempted to regulate the proliferation and function of cells transplanted into mice in a short period of time using the iC9 gene and AP20187. We examined whether AP20187 treatment was able to rapidly regulate the proliferation and function of iC9 gene-expressing cells after transplantation into mice
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