Effect of the Soluble Factors Released by Dental Apical Papilla-Derived Stem Cells on the Osteo/Odontogenic, Angiogenic, and Neurogenic Differentiation of Dental Pulp Cells.

Stem cells derived from dental apical papilla (SCAPs) can secrete various soluble factors, which may stimulate tissue repair and regeneration in vivo. The aim of this study was to elucidate the effect of the soluble factors released by SCAPs on the proliferation and differentiation of dental pulp cells (DPCs). We compared the osteo/odontogenic, angiogenic, and neurogenic effects of soluble factors released from SCAPs and bone marrow mesenchymal stem cells (BMSCs) in vitro. Conditioned media (CM) were collected from human SCAPs and BMSCs cultures, and their effects on human DPCs proliferation and differentiation were evaluated. Cellular proliferation was unaffected by SCAPs-CM and was inhibited by BMSCs-CM. Cells treated with osteo/odontogenic inducing medium (OM) plus SCAPs-CM showed higher alkaline phosphatase activity than did cells in the OM group. The expression level of osteo/odontogenic markers were higher in the SCAPs-CM plus OM group than in the BMSCs-CM plus OM and OM groups. SCAPs-CM and BMSCs-CM significantly promoted DPCs migration. DPCs angiogenic differentiation was not affected by SCAPs-CM but was significantly enhanced by BMSCs-CM. In DPCs cultured in media optimized for neural stem cell growth for 2 weeks, the expression levels of neurogenic markers were significantly enhanced by the addition of SCAPs-CM. Neuronal markers expression was significantly reduced, while neurotrophic marker expression significantly increased by the addition of BMSCs-CM. In conclusion, SCAPs-CM significantly enhanced osteo/odontogenic differentiation, migration, and neurogenic differentiation potential of DPCs, but have no effect on DPCs proliferation and angiogenic differentiation in vitro. CM released from SCAPs have a greater osteo/odontogenic and neurogenic inductive effect on DPCs than BMSCs-CM. It indicates that SCAPs-CM can serve as additive to improve pulp tissue repair and regeneration.