LAUSR

Introduction: The aim of this study was to measure and compare the expression levels of cytokines from developing apical complex cells (DACCs) and dental pulp stem cells (DPSCs) of the immature tooth. Methods: DPSC‐conditioned medium (CM) and DACCs‐CM were obtained from human young teeth, and 174 cytokines secreted from each CM were identified and compared. A cytokine membrane array and enzyme‐linked immunosorbent assay were used to measure and compare the expression levels of the cytokines. Immunocytochemistry targeting insulin‐like growth factor‐1 and neurotrophin‐3 was additionally performed. Results: There were statistically significant differences in the expression levels of 25 cytokines: 22 and 3 were expressed more strongly in DPSCs‐CM and DACCs‐CM, respectively. Odontoblast differentiation‐related cytokines were more strongly expressed in DPSCs‐CM, while cell‐proliferation–related cytokines were more strongly expressed in DACCs‐CM. Proinflammatory and anti‐inflammatory cytokines were predominantly expressed in DPSCs‐CM and DACCs‐CM, respectively. Conclusions: DPSCs may exert a stronger paracrine effect than DACCs on regeneration of the dentin–pulp complex, in terms of odontoblast differentiation. HighlightsThis study compared the expression levels of different cytokines using a cytokine membrane array, with additional enzyme‐linked immunosorbent assay and immunocytochemistry (ICC) tests performed to elucidate the paracrine effects of DPSCs and DACCs.Cytokines associated with odontoblast differentiation (NT‐3, BMP‐4, TGF‐&bgr;1, and TGF‐&bgr;3) were expressed more strongly in DPSCs than in DACCs. It could be suggested that cytokines expressed in DPSCs provide a more suitable environment for odontoblast differentiation for the same epigenetic signals.The secretion level of cell‐proliferation–related cytokines was higher for DACCs than for DPSCs. The stronger expression of proliferation cytokines observed in this study corroborates the high proliferation activity of the DACCs found in previous in vitro studies. Thus, the developing apical complex of the young tooth acts as a growth center via the proliferation ability of cytokines expressed in the periphery.This study is the first to attempt to measure and compare the expression levels of cytokines from DACCs and DPSCs of immature teeth. The findings have demonstrated that DPSCs may exert a stronger paracrine effect than DACCs on regeneration of the dentin–pulp complex, in terms of odontoblast differentiation.