ABSTRACT
Dental pulp stem cells (DPSCs) are mesenchymal stem cells (MSCs) with the potential to differentiate in a limited number of other tissue types. Some evidence has suggested the modulation of DPSC growth may be mediated, in part, by exogenous extracellular matrix (ECM) glycoproteins, including fibronectin (FN) and laminin-5 (LN5). Although preliminary research suggests that some ECM glycoproteins may work as functional biomaterials to modulate DPSC growth responses, the primary goal of this project is to determine the specific effects of FN and LN5 on DPSC growth and viability. Using an existing DPSC repository, n = 16 DPSC isolates were cultured and 96-well growth assays were performed, which revealed FN, LN5 and the combination of these were sufficient to induce statistically significant changes in growth among five (n = 5) DPSC isolates. In addition, the administration of FN (either alone or in combination) was sufficient to induce the expression of alkaline phosphatase (ALP) and dentin sialophosphoprotein (DSPP), while LN5 induced the expression of ALP only, suggesting differential responsiveness among DPSCs. Moreover, these responses appeared to correlate with the expression of MSC biomarkers NANOG, Oct4 and Sox2. These results add to the growing body of evidence suggesting that functional biomaterials, such as ECM glycoproteins FN and LN5, are sufficient to induce phenotypic and differentiation-specific effects in a specific subset of DPSC isolates. More research will be needed to determine which biomarkers or additional factors are necessary and sufficient to induce the differentiation and development of DPSCs ex vivo and in vitro for biomedical applications.
ABSTRACT
INTRODUCTION: 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 growth, viability, and proliferation, as well as differentiation of DPSC-although much remains to be discovered. Based upon this information, the primary objective of this study was to understand the functional biomaterials needed to more effectively direct DPSC viability, growth, and proliferation. METHODS: Using an approved protocol, previously collected and isolated samples of DPSC from an existing repository were used. 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 functional 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 functional 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 growth, viability, and differentiation potential, more research is needed to determine the other intrinsic and extrinsic factors that may contribute to and modulate these DPSC responses to these functional biomaterials for biotechnology and bioengineering applications.
ABSTRACT
BACKGROUND: Uric acid has been reported to function both as an oxidant or antioxidant depending on the context. A previous study in the Korean population reported a positive linear association between serum uric acid level and arterial stiffness in men, but little is known about how serum uric acid level is related to the risk of increased arterial stiffness in Korean postmenopausal women. METHODS: We performed a cross-sectional study of 293 subjects who participated in a health examination program run by the health promotion center of Gangnam Severance Hospital between October 2007 and July 2010. High brachial-ankle pulse wave velocity was defined as a brachial-ankle pulse wave velocity of more than 1,450 cm/s. The odds ratios (ORs) for high brachial-ankle pulse wave velocity were calculated using multivariate logistic regression analysis across uric acid quartiles after adjusting for other indicators of cardiovascular risk. RESULTS: The 293 postmenopausal women were divided into quartiles according to uric acid level. The mean brachial-ankle pulse wave velocity values of each quartile were as follows: Q1, 1,474 cm/s; Q2, 1,375 cm/s; Q3, 1,422 cm/s; Q4, 1,528 cm/s. The second quartile was designated as the control group based on mean brachial-ankle pulse wave velocity value. Multivariate adjusted ORs (95% confidence intervals) for brachial-ankle pulse wave velocity across the uric acid quartiles were 2.642 (Q1, 1.095-6.3373), 1.00, 4.305 (Q3, 1.798-10.307), and 4.375 (Q4, 1.923-9.949), after adjusting for confounding variables. CONCLUSION: Serum uric acid level has a J-shaped association with arterial stiffness in Korean postmenopausal women.
