SHED Differentiate into Functional Odontoblasts and Endothelium

TLDR

Understanding how dental pulp stem cells differentiate is essential for odontogenesis biology and dental tissue engineering. The study tests whether stem cells from exfoliated deciduous teeth (SHED) can differentiate into functional odontoblasts and endothelial cells. SHED were cultured on tooth slices and implanted subcutaneously in immunodeficient mice, and VEGF stimulation in vitro induced endothelial marker expression and capillary‑like sprout formation. SHED formed tubular dentin as odontoblasts and differentiated into vascular endothelial cells, and VEGF drove ERK/AKT activation while inhibiting STAT3, demonstrating their capacity to generate angiogenic endothelial cells and odontoblasts that produce tubular dentin.

Abstract

Studies on mechanisms underlying the differentiation of dental pulp stem cells are critical for the understanding of the biology of odontogenesis and for dental tissue engineering. Here, we tested the hypothesis that stem cells from exfoliated deciduous teeth (SHED) differentiate into functional odontoblasts and endothelial cells. SHED were seeded in tooth slice/scaffolds and implanted subcutaneously into immunodeficient mice. SHED differentiated into functional odontoblasts that generated tubular dentin, as determined by tetracycline staining and confocal microscopy. These cells also differentiated into vascular endothelial cells, as determined by beta-galactosidase staining of LacZ-tagged SHED. In vitro, vascular endothelial growth factor (VEGF) induced SHED to express VEGFR2, CD31, and VE-Cadherin (markers of endothelium) and to organize into capillary-like sprouts. VEGF induced ERK and AKT phosphorylation (indicative of differentiation), while inhibiting phosphorylation of STAT3 (indicative of ‘stemness’). Collectively, this work demonstrates that SHED can differentiate into angiogenic endothelial cells and odontoblasts capable of generating tubular dentin.