Human olfactory stem cells: As a promising source of dopaminergic neuron-like cells for treatment of Parkinson's disease

Neurosci Lett. 2019 Mar 23:696:52-59. doi: 10.1016/j.neulet.2018.12.011. Epub 2018 Dec 12.

Abstract

The production of dopaminergic (DA) neurons from stem cells holds a great promise for future clinical treatment of neurodegenerative diseases, such as Parkinson's disease (PD). Olfactory ecto-mesenchymal stem cells (OE-MSCs) derived from the adult human olfactory mucosa can be easily isolated and expanded in culture while maintaining their immense plasticity. In addition to reduced ethical concerns, OE-MSCs could be transplanted across allogeneic barriers, making them desirable stem cells for clinical applications. The goal of this study was to define the potentiality of human olfactory mucosa-derived MSCs aimed at differentiation into DA neuron-like cells. OE-MSCs were induced to differentiate to DA neuron-like cells in vitro by using sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF), Glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). Then the differentiated neurons were characterized for expression of DA neuron markers by Real-time PCR, immunocytochemistry and flow cytometry. Our findings showed that differentiated OE-MSCs could significantly express DA neuron markers at mRNA and protein levels along with dopamine release 12 days post-differentiation. These results support the viability and feasibility of using OE-MSCs as a source of in vitro generated DA neuron-like cells for treatment of DA disorders namely PD.

Keywords: Dopamine producing cells; Dopaminergic neuron-like cells; Human olfactory mucosa; In vitro differentiation; Olfactory ecto-mesenchymal stem cells; Parkinson’s disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology
  • Cell- and Tissue-Based Therapy* / methods
  • Cells, Cultured
  • Dopamine / metabolism
  • Dopaminergic Neurons / metabolism*
  • Hedgehog Proteins / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Olfactory Bulb / cytology*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / therapy

Substances

  • Hedgehog Proteins
  • Dopamine