Differentiation of stem cells from human deciduous and permanent teeth into spiral ganglion neuron-like cells

Arch Oral Biol. 2018 Apr:88:34-41. doi: 10.1016/j.archoralbio.2018.01.011. Epub 2018 Feb 2.

Abstract

Objective: Stem cells from pulp tissue are a promising cell-based therapy for neurodegenerative patients based on their origin in the neural crest. The aim of this study was to differentiate and evaluate the ability of human dental pulp stem cells from permanent teeth (DPSC) and stem cells from human exfoliated deciduous teeth (SHED) to differentiate into spiral ganglion neurons.

Design: After isolation and characterization of mesenchymal stem cell properties, DPSC and SHED were treated with the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial cell-derived neurotrophic factor (GDNF). The differentiation was identified by immunostaining and qRT-PCR analysis of neuronal markers and measuring intracellular calcium activity.

Results: After 2 weeks of induction, morphological changes were observed in both DPSC and SHED. The differentiated cells expressed neuron-specific class III beta-tubulin, GATA binding protein 3 (GATA3) and tropomyosin receptor kinase B, protein markers of spiral ganglion neurons. These cells also showed upregulation of the genes encoding these proteins, namely GATA3 and neurotrophic receptor tyrosine kinase 2. Intracellular calcium dynamics that reflect neurotransmitter release were observed in differentiated DPSC and SHED.

Conclusion: These results demonstrate that dental pulp stem cells from permanent and deciduous teeth can differentiate into spiral ganglion neuron-like cells.

Keywords: Dental pulp stem cells; Neurotrophins; Spiral ganglion neuron; Stem cells from human exfoliated deciduous teeth (SHED).

MeSH terms

  • Antigens, Surface / analysis
  • Antigens, Surface / metabolism
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Plasticity
  • Dental Pulp / cytology*
  • Dentition, Permanent*
  • Fibroblasts / cytology
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism
  • Gene Expression
  • Glial Cell Line-Derived Neurotrophic Factor / pharmacology
  • Hearing Loss / therapy
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Nerve Growth Factors / pharmacology
  • Neurons / cytology*
  • Neurotrophin 3
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism
  • Spiral Ganglion / cytology*
  • Spiral Ganglion / metabolism*
  • Tooth, Deciduous / cytology*
  • Tubulin / genetics
  • Tubulin / metabolism
  • Up-Regulation

Substances

  • Antigens, Surface
  • Brain-Derived Neurotrophic Factor
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • NTF3 protein, human
  • Nerve Growth Factors
  • Neurotrophin 3
  • TUBB3 protein, human
  • Tubulin
  • Receptor, trkB
  • tropomyosin-related kinase-B, human