Advances in Dental Pulp Stem Cell Biology for Biomedical Engineering (Preprint)
BACKGROUND Many studies in stem cell biology have demonstrated that dental pulp stem cells (DPSC) may be highly proliferative and capable of pluripotent differentiation into many different tissue types. Recent advances in stem cell research have outlined methods for directing in vitro or in vivo differentiation of DPSC - although much remains to be discovered. OBJECTIVE Based upon this information, the primary objective of this study was to understand the biology and biotechnology needed to more effectively direct DPSC differentiation. METHODS Previously collected and isolated samples of DPSC from an existing repository were used. Due to the use of previously collected, non-identifiable samples this protocol was granted exemption from Human Subjects review. Previously established stem cell biomarkers (Sox-2, Oct-4, NANOG) from each isolate were correlated with their proliferation rates or doubling times to categorize them into rapid, intermediate, or slow-dividing multipotent DPSC. Growth factors and other dental biomaterials were subsequently tested to evaluate DPSC responses in proliferation, viability and morphology. RESULTS Differential responses were observed among DPSC isolates to growth factors, including vascular endothelial growth factor (VEGF) and bone morphogenic protein (BMP-2), and biomaterials such as mineralized trioxide aggregates (MTA). The responsiveness of DPSC isolates did not correlate with any single factor but rather with a combination of proliferation rate and biomarker expression. CONCLUSIONS These data strongly suggest that some, but not all DPSC isolates are capable of a robust and significant in vitro response to differentiation stimuli, although this response is not universal. Although some biomarkers and phenotypes that distinguish and characterize these DPSC isolates may facilitate the ability to predict differentiation potential, more research is needed to determine the other intrinsic and extrinsic factors that may contribute to and modulate these DPSC responses for biotechnology and bioengineering applications. CLINICALTRIAL N/A (not applicable)