Wnt-activated olfactory ensheathing cells stimulate neural stem cell proliferation and neuronal differentiation

Brain Res. 2020 May 15:1735:146726. doi: 10.1016/j.brainres.2020.146726. Epub 2020 Feb 10.

Abstract

Olfactory ensheathing cells (OECs) are special glial cells localized in olfactory system which secrete large number of neurotrophic factors and promote the migration and survival of neurons. Canonical Wnt/β-catenin signaling is activated in OECs during development and facilitates the growth and regeneration of axons. In the present study, we investigated the effects of Wnt-activated OECs on the proliferation and differentiation of neural stem cells (NSCs) in vitro. Primary neonatal mouse OECs were cultured and identified by immunostaining of P75 and GFAP. Wnt activation was achieved by lentivirus transfection of dominant-active-β-catenin (EbC) and examined by immunostaining of PY489. The conditioned medium (CM) of Wnt-activated OECs (wOECs-CM) and control OECs (cOECs-CM) was used to stimulate NSCs. In proliferation assay, wOECs-CM could increase the percentage of Ki67/Sox2 double positive cells. Under differentiation condition, wOECs-CM could maintain the expression of Nestin and promote the differentiation of NSCs into Tuj1-positive neurons. Taken together, our data revealed that wOECs stimulates the proliferation and differentiation of NSCs in a secretory manner, indicating that combined transplantation of wOECs and NSCs may be beneficial for regeneration.

Keywords: Differentiation; Neural stem cells; Olfactory ensheathing cells; Proliferation; Wnt signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Coculture Techniques
  • Culture Media, Conditioned / chemistry
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Growth Factors / metabolism
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / physiology
  • Neuroglia / metabolism
  • Neurons / metabolism*
  • Olfactory Bulb / metabolism*
  • Smell / physiology
  • Wnt Signaling Pathway / physiology
  • Wnt1 Protein / metabolism
  • Wnt1 Protein / physiology

Substances

  • Culture Media, Conditioned
  • Nerve Growth Factors
  • Wnt1 Protein
  • Wnt1 protein, mouse