Cell-based neural regeneration is challenging due to the difficulty in obtaining sufficient neural stem cells with clinical applicability. Stem cells from apical papilla (SCAPs) originating from embryonic neural crests with high neurogenic potential could be a promising cell source for neural regeneration. This study aimed to investigate whether the formation of 3D spheres can promote SCAPs' neurogenic potential.

Recently, a new strategy has been developed to directly reprogram one cell type towards another targeted cell type using small molecule compounds. Human fibroblasts have been chemically reprogrammed into neuronal cells, Schwann cells and cardiomyocyte-like cells by different small molecule combinations. This study aimed to explore whether stem cells from apical papilla (SCAP) could be reprogrammed into endothelial cells (ECs) using the same strategy.

Osteo/odontogenic differentiation is a key process of human stem cells from apical papilla (SCAP) in tooth root development. Emerging evidence indicates microRNAs (miRNAs) play diverse roles in osteogenesis. However, their functions in osteo/odontogenic differentiation of SCAP require further elucidation. To investigate the role of miRNA in SCAP osteo/odontogenic differentiation and underlying mechanisms, miRNA microarray analysis was performed to screen differentially expressed miRNAs between control and osteo/odontogenic-induced group. Quantitative real-time PCR (qRT-PCR) and western blot were used to detected osteo/odontogenic differentiation-related markers and possible signaling pathway SCAP-associated genes. Alizarin Red Staining (ARS) were applied to evaluated osteogenic capacity. The results showed that miR-497-5p increased during SCAP osteo/odontogenic differentiation. Overexpression of miR-497-5p enhanced the osteo/odontogenic differentiation of SCAP, whereas downregulation of miR-497-5p elicited the opposite effect, thus suggesting that miR-497-5p is a positive regulator of the osteo/odontogenic differentiation of SCAP. Bioinformatic analysis and dual luciferase reporter assay identified that SMAD specific E3 ubiquitin protein ligase 2 (Smurf2) is a direct target of miR-497-5p. Further study demonstrated that Smurf2 negatively regulates SCAP osteo/odontogenic differentiation, and silencing Smurf2 could block the inhibitory effect of the miR-497-5p inhibitor. Meanwhile, pathway detection manifested that miR-497-5p promotes osteo/odontogenic differentiation via Smad signaling pathway. Collectively, our findings demostrate that miR-497-5p promotes osteo/odontogenic differentiation of SCAP via Smad signaling pathway by targeting Smurf2.

Dental-derived stem cells originate from the embryonic neural crest, and exhibit high neurogenic potential. This study aimed to investigate whether a cocktail of eight small molecules (Valproic acid, CHIR99021, Repsox, Forskolin, SP600125, GO6983, Y-27632 and Dorsomorphin) can enhance the in vitro neurogenic differentiation of dental pulp stem cells (DPSCs), stem cells from apical papilla (SCAPs) and gingival mesenchymal stem cells (GMSCs), as a preliminary step towards clinical applications.