Project R-6891

Dental pulp stem cells as an innovative tool to specifically target angiogenesis in oral squamous cancer (Research)

Head and neck squamous cell cancers (HNSCC) are among the most prevalent tumors in the world. Despite recent advances in treatment, the survival rate of patients has remained incredibly poor and unchanged during the past 30 years. The aggressive behavior of HNSSC is associated with angiogenesis, indicating that inhibiting this phenomenon would provide an effective therapy. Emerging evidence indicates that bone-marrow mesenchymal stem cells (BM-MSCs) are able to specifically home to tumors and thus could be used as effective delivery vehicles for anti-angiogenic proteins. As harvesting BM-MSCs is painful, invasive and often causes complications, our goal is to use dental pulp stem cells (hDPSCs), MSC-like cells with even superior properties than BM-MSCs, isolated from human teeth. First, we investigate the effect of unmodified hDPSCs in a HNSCC xenograft mouse model in combination with optical bioluminescent imaging, which allows the non-invasive and simultaneous monitoring of tumor progression, hDPSC survival and localization. Next, hDPSCs are engineered to stably express thrombospondin-1, one of the most potent anti-angiogenic proteins and the antitumoral effect of these modified hDPSCs in the aforementioned mouse model is examined. Our findings do not only have implications in the fight against cancer but may also reveal whether hDPSCs could be safely used in the clinic to treat other diseases including stroke, spinal cord injury and myocardial infarction.

01 January 2016 - 31 December 2018