Hypoxia Modulates the Differentiation Potential of Stem Cells of the Apical Papilla
Copyright policy )Hypoxia Modulates the Differentiation Potential of Stem Cells of the Apical Papilla
Stem cells from the apical papilla (SCAP) are a population of mesenchymal stem cells likely involved in regenerative endodontic procedures and have potential use as therapeutic agents in other tissues. In these situations, SCAP are exposed to hypoxic conditions either within a root canal devoid of an adequate blood supply or in a scaffold material immediately after implantation. However, the effect of hypoxia on SCAP proliferation and differentiation is largely unknown. Therefore, the objective of this study was to evaluate the effect of hypoxia on the fate of SCAP.SCAP were cultured under normoxia (21% O2) or hypoxia (1% O2) in basal or differentiation media. Cellular proliferation, gene expression, differentiation, and protein secretion were analyzed by live imaging, quantitative reverse-transcriptase polymerase chain reaction, cellular staining, and enzyme-linked immunosorbent assay, respectively.Hypoxia had no effect on SCAP proliferation, but it evoked the up-regulation of genes specific for osteogenic differentiation (runt-related transcription factor 2, alkaline phosphatase, and transforming growth factor-β1), neuronal differentiation ( 2'-3'-cyclic nucleotide 3' phosphodiesterase, SNAIL, neuronspecific enolase, glial cell-derived neurotrophic factor and neurotrophin 3), and angiogenesis (vascular endothelial growth factor A and B). Hypoxia also increased the sustained production of VEGFa by SCAP. Moreover, hypoxia augmented the neuronal differentiation of SCAP in the presence of differentiation exogenous factors as detected by the up-regulation of NSE, VEGFB, and GDNF and the expression of neuronal markers (PanF and NeuN).This study shows that hypoxia induces spontaneous differentiation of SCAP into osteogenic and neurogenic lineages while maintaining the release of the proangiogenic factor VEGFa. This highlights the potential of SCAP to promote pulp-dentin regeneration. Moreover, SCAP may represent potential therapeutic agents for neurodegenerative conditions because of their robust differentiation potential.
- Université Catholique de Louvain Belgium
- University of Geneva Switzerland
- The University of Texas Health Science Center at San Antonio United States
Cell Culture Techniques, Neurodifferentiation, Core Binding Factor Alpha 1 Subunit, 2',3'-Cyclic-Nucleotide Phosphodiesterases / analysis, Transcription Factors / analysis, Dental Papilla / cytology, Neurotrophin 3, Osteogenesis, Core Binding Factor Alpha 1 Subunit / analysis, Dental Pulp / cytology, Hypoxia, Adipogenesis, Neurogenesis / physiology, Cell Differentiation, Cell Hypoxia, Alkaline Phosphatase / analysis, Female, 2',3'-Cyclic-Nucleotide Phosphodiesterases, Apical papilla, Adolescent, Adipogenesis / physiology, Neurogenesis, Mesenchymal Stem Cells / physiology, Osteogenesis / physiology, Neurotrophin 3 / analysis, Regenerative endodontics, Vascular Endothelial Growth Factor B / analysis, Humans, Glial Cell Line-Derived Neurotrophic Factor, Dental Papilla, Stem cells from the apical papilla, Dental Pulp, Cell Proliferation, Transforming Growth Factor beta1 / analysis, Mesenchymal Stem Cells, Vascular Endothelial Growth Factor A / analysis, Alkaline Phosphatase, Angiogenic factor, Culture Media, Cell Hypoxia / physiology, Phosphopyruvate Hydratase / analysis, Dental stem cells, Glial Cell Line-Derived Neurotrophic Factor / analysis, Phosphopyruvate Hydratase, Gene expression, Cell Differentiation / physiology, Snail Family Transcription Factors
Cell Culture Techniques, Neurodifferentiation, Core Binding Factor Alpha 1 Subunit, 2',3'-Cyclic-Nucleotide Phosphodiesterases / analysis, Transcription Factors / analysis, Dental Papilla / cytology, Neurotrophin 3, Osteogenesis, Core Binding Factor Alpha 1 Subunit / analysis, Dental Pulp / cytology, Hypoxia, Adipogenesis, Neurogenesis / physiology, Cell Differentiation, Cell Hypoxia, Alkaline Phosphatase / analysis, Female, 2',3'-Cyclic-Nucleotide Phosphodiesterases, Apical papilla, Adolescent, Adipogenesis / physiology, Neurogenesis, Mesenchymal Stem Cells / physiology, Osteogenesis / physiology, Neurotrophin 3 / analysis, Regenerative endodontics, Vascular Endothelial Growth Factor B / analysis, Humans, Glial Cell Line-Derived Neurotrophic Factor, Dental Papilla, Stem cells from the apical papilla, Dental Pulp, Cell Proliferation, Transforming Growth Factor beta1 / analysis, Mesenchymal Stem Cells, Vascular Endothelial Growth Factor A / analysis, Alkaline Phosphatase, Angiogenic factor, Culture Media, Cell Hypoxia / physiology, Phosphopyruvate Hydratase / analysis, Dental stem cells, Glial Cell Line-Derived Neurotrophic Factor / analysis, Phosphopyruvate Hydratase, Gene expression, Cell Differentiation / physiology, Snail Family Transcription Factors
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