High expression of TRAIL by osteoblastic differentiated dental pulp stem cells affects myeloma cell viability

Cells from dental tissues have a mesenchymal stem cell (MSC) phenotype, are multipotent and can differ- entiate into osteoblastic cells, as we have previously found. MSCs, due to their tumor-homing ability, are currently being used as cell-based delivery systems for cancer protein thera- peutics, such as the TNF-related apoptosis-inducing ligand (TRAIL). In the present study we revealed that dental pulp stem cells (DPSCs) expressed TRAIL to a greater extent when they were differentiated into the osteoblastic lineage. TRAIL affected the viability of undifferentiated DPSCs, while osteoblastic differentiated DPSCs were not sensitive to TRAIL. The expression trend of TRAIL receptors underwent changes during the osteoblastic differentiation of DPSCs exhibiting low DcR2 and high DR5 levels in the undifferen- tiated DPSCs and an opposite scenario was presented in the differentiated cells. The sensitivity of the undifferentiated DPSCs to the TRAIL-apoptotic effect was also associated with low levels of intracellular anti-apoptotic proteins, such as c-FLIP, XIAP and the activation of caspase-8 and -3. DPSC-differentiated osteoblasts expressing high TRAIL levels were capable to affect the cell viability of the human myeloma cell line H929, thus representing an effective anti- cancer therapeutic method.