Et-5 potent bystander effect in suicide gene therapy using tk-expressing stem cells from human exfoliated deciduous teeth

Abstract Introduction We investigated HSVTK/GCV suicide gene therapy for malignant glioma, and demonstrated the migration ability and antitumor effect of various tissue-derived pluripotent stem cells. In recent years, stem cells from human exfoliated deciduous teeth (SHED), which have excellent ethical and self-renewal ability, have attracted attention, especially in regenerative medicine. In this study, using SHEDTK transfected with TK, we examined the migration ability and antitumor effect against malignant glioma and metastasis models. Methods In vitro assay: Using Matrigel chamber, the migration ability of SHEDTK to conditioned medium (CM) of glioma cells, lung carcinoma cells, and various tumor growth factors (TGF) was examined. The antitumor effect was examined for cell viability by co-culturing SHEDTK and each tumor cell under the addition of GCV. in vivo assay: Using glioma model mice, SHEDTK migrating around the tumor was confirmed in brain sections. In addition, we co-implanted SHEDTK and administered GCV to glioma and metastasis model as therapeutic models, evaluated tumor reduction effect by bioluminescence, and confirmed survival curves. Results In vitro assay: SHEDTK significantly migrated to CM and TGF compared to control. The antitumor effect was observed even when the ratio of each tumor cell to SHEDTK was 128-256 times. in vivo assay: In glioma model mice, SHEDTK migrated around contralateral tumor. In the treatment experiment, the control group died of tumors, whereas the tumor in the treatment group disappeared within the period of GCV administration, and they survived without neurological deficits until 100 days later, and the overall survival time was improved with a statistically significant difference. Conclusions We confirmed the migration ability and antitumor effect of SHEDTK on malignant glioma and metastasis models. Suicide gene therapy using SHEDTK was suggested as novel gene therapy. In the future, we plan to conduct translational research such as preclinical studies and physician -initiated clinical trials.