Differentiation of human olfactory system-derived stem cells into dopaminergic neuron-like cells: A comparison between olfactory bulb and mucosa as two sources of stem cells

J Cell Biochem. 2019 Dec;120(12):19712-19720. doi: 10.1002/jcb.29277. Epub 2019 Jul 11.

Abstract

Cell transplantation has become a possible therapeutic approach in the treatment of neurodegenerative diseases of the nervous system by replacing lost cells. The current study aimed to make a comparison between the differentiation capacity of the olfactory bulb neural stem cells (OB-NSCs) and olfactory ectomesenchymal stem cells (OE-MSCs) into dopaminergic-like neurons under the inductive effect of transforming growth factor β (TGF-β). After culturing and treating with TGF-β, the differentiation capacities of both types of stem cells into dopaminergic neuron-like cells were evaluated. Quantitative real-time polymerase chain reaction analysis 3 weeks after induction demonstrated that the mRNA expression of the dopaminergic activity markers tyrosine hydroxylase (TH), dopamine transporter (DAT), paired box gene 2 (PAX2), and PAX5 in the neuron-like cells derived from OB-NSCs was significantly higher than those derived from OE-MSCs. These findings were further supported by the immunocytochemistry staining showing that the expression of the tyrosine hydroxylase, DAT, PAX2, and paired like homeodomain 3 seemed to be slightly higher in OB-NSCs compared with OE-MSCs. Despite the lower differentiation capacity of OE-MSCs, other considerations such as a noninvasive and easier harvesting process, faster proliferation attributes, longer life span, autologous transplantability, and also the easier and inexpensive cultural process of the OE-MSCs, cumulatively make these cells the more appropriate alternative in the case of autologous transplantation during the treatment process of neurodegenerative disorders like Parkinson's disease.

Keywords: dopaminergic neurons; ectomesenchymal stem cells; neural stem cells; olfactory bulb; olfactory mucosa.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopaminergic Neurons / cytology*
  • Dopaminergic Neurons / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mucous Membrane / cytology
  • Neural Stem Cells / cytology
  • Olfactory Bulb / cytology*
  • PAX2 Transcription Factor / genetics
  • PAX5 Transcription Factor / genetics
  • Stem Cells / cytology*
  • Stem Cells / physiology
  • Transforming Growth Factor beta / pharmacology
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • PAX2 Transcription Factor
  • PAX2 protein, human
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • Transforming Growth Factor beta
  • Tyrosine 3-Monooxygenase