Stem cell therapy based on human periodontal ligament stem cells preactivated with TNF-α as for human head and neck squamous cell carcinoma

Abstract

ObjectiveMesenchymal stem cells (MSCs) express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) following activation by various molecules and have antitumor effects against several cancer types. In particular, preactivation of MSCs with tumor necrosis factor-α (TNF-α) enhances TRAIL expression. We focused on the application of human periodontal ligament-derived stem cells (hPDLSCs) to stem cell-based cancer therapy, and evaluated their effects on head and neck squamous cell carcinoma (HNSCC) cells. MethodsTRAIL expression in hPDLSCs preactivated with TNF-α (A-hPDLSCs) was evaluated using real-time PCR, western blotting, and fluorescent immunocytochemistry. Subsequently, non-treated hPDLSCs (N-hPDLSCs) or A-hPDLSCs were cocultured with three types of HNSCC cells: HSC2, HSC3, and HSC4, and HNSCC cell apoptosis was assessed using flow cytometry. The migration ability of N-hPDLSCs and A-hPDLSCs toward HNSCC cells was also evaluated using a 3D gel invasion assay. In addition, conditioned medium (CM) derived from A-hPDLSCs was added to HNSCC cells, and cell proliferation ability was measured. ResultsA-hPDLSCs preactivated with 10 ng/mL TNF-α significantly upregulated the expression of TRAIL, increased apoptosis in HNSCC cells, and exhibited increased migration toward HNSCC cells compared to N-hPDLSCs. However, CM derived from A-hPDLSCs neither increased apoptosis nor suppressed HNSCC cell proliferation. ConclusionshPDLSCs are proposed to be beneficial for stem cell therapies for HNSCC. Upon TNF-α preactivation, hPDLSCs may migrate toward HNSCC cells and directly induce apoptosis.