Human dental pulp stem cells as a potential carrier for the herpes simplex-1 virus thymidine kinase suicide gene for therapy of oral squamous cell carcinoma and characterization of the 4-nitroquinoline-1-oxide rat model

Abstract

In 2018, 2.5% of all cancers could be attributed to oral cancer. Over 90% of these oral cancers belong to the class of oral squamous cell carcinoma (OSCC), which are malignancies that originate from the oral cavity and oropharynx. The survival rates have been consistent in recent decades despite numerous advances in research and therapy. Surgical resection of the oral floor or tongue leads to complications in mastication, speech and altered aesthetics. Furthermore, radio- and chemotherapy hold a high risk of tumor recurrence and adverse effects such as xerostomia. The herpes simplex virus 1-thymidine kinase (HSV1-tk) mechanism is proposed to address these side effects. Transduction of cells with the HSV1-tk suicide gene renders the cells capable to modify ganciclovir, metabolically trapping it and leading to apoptosis. To date, lentiviral vectors are used to introduce the transgene into cancer cells; however, these vectors are a suboptimal delivery system associated with safety issues. Cellular vehicles such as human dental pulp stem cells (hDPSCs) could address these issues. Human DPSCs are a subtype of mesenchymal stem cells which are known to migrate to tumorous tissue and hence, can be an ideal candidate to carry the suicide gene to the tumor. Additionally, the mutant HSV1-sr39-tk holds a higher efficiency towards ganciclovir (GCV). Therefore, we hypothesized that therapy with HSV1-sr39-tk+ hDPSCs results in the death of OSCC cells through the bystander effect and elicits a subsequent reduction of tumor size.