Abstract
INTRODUCTION: Over 60,000 new cases of head and neck cancer were diagnosed in the U.S. in 2016. Radiation is commonly required to reduce recurrence rates and improve survival; however, complications after radiation, including poor bone healing and osteoradionecrosis, contribute to the significant morbidity associated with this disease process. The current standard of treatment of such complications is limited to free tissue transfer. Given the significant morbidity associated with these procedures, it is important to examine the utility of cell-based therapies as a potential translational treatment to promote bone regeneration for irradiated patients. Adipose-derived stem cells (ASCs) and bone marrow derived stem cells (BMSCs) represent translational therapies that can improve osteogenesis. We recently demonstrated that ASCs are superior to BMSCs in enhancing bone healing using a segmental defect model in the rat mandible. We hypothesize that differing mechanisms of action between the two cell types contribute to the superiority of ASC’s to enhance bone healing. METHODS: BMSCs and ASCs were harvested from male Lewis rats (n=3), plated at a density of 200,000 cells/well, and treated with osteogenic differentiation medium. Alkaline phosphatase stain was performed to evaluate osteogenic potential. Vascular endothelial growth factor (VEGF) was also measured and compared. Finally, ASCs and BMSCs were cocultured with human umbilical vein endothelial cells using a transwell system to study the paracrine effect of these two cell types on vasculogenesis. Student’s t-tests were used to compare the osteogenic and vasculogenic potential of the two groups. RESULTS: ASCs had significantly less osteogenic potential than BMSCs (11.8 ± 0.9 vs. 16.3 ± 0.4; p<0.05). Conversely, ASCs were significantly more vasculogenic than BMSCs based on VEGF release (3,573 ± 87.4 vs. 1607.0 ± 45.0; p<0.001). These findings translated to significantly greater tubule formation in transwells treated with ASCs compared to BMSCs on video microscopy. The properties of ASCs that resulted in enhanced vasculogenesis are associated with enhanced bone formation in vivo and improved healing in our segmental defect model. CONCLUSION: ASCs and BMSCs enhance bone formation via different mechanisms. While to enhance bone healing as described in this study, the mechanism of a vasculogenic intermediate may hold greater promise in creating a translational therapeutic that more proficiently promotes bone healing and remediates the ravages of radiation injury.
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