Abstract

BackgroundThe olfactory epithelium is a neurogenic tissue comprising a population of olfactory receptor neurons that are renewed throughout adulthood by a population of stem and progenitor cells. Because of their relative accessibility compared to intra-cranially located neural stem/progenitor cells, olfactory epithelium stem and progenitor cells make attractive candidates for autologous cell-based therapy. However, olfactory stem and progenitor cells expand very slowly when grown as free-floating spheres (olfactory-spheres) under growth factor stimulation in a neurosphere assay.ResultsIn order to address whether olfactory mucosa cells extrinsically regulate proliferation and/or differentiation of immature neural cells, we cultured neural progenitor cells derived from mouse neonatal olfactory bulb or subventricular zone (SVZ) in the presence of medium conditioned by olfactory mucosa-derived spheres (olfactory-spheres). Our data demonstrated that olfactory mucosa cells produced soluble factors that affect bulbar neural progenitor cell differentiation but not their proliferation when compared to control media. In addition, olfactory mucosa derived soluble factors increased neurogenesis, especially favouring the generation of non-GABAergic neurons. Olfactory mucosa conditioned medium also contained several factors with neurotrophic/neuroprotective properties. Olfactory-sphere conditioned medium did not affect proliferation or differentiation of SVZ-derived neural progenitors.ConclusionThese data suggest that the olfactory mucosa does not contain factors that are inhibitory to neural stem/progenitor cell proliferation but does contain factors that steer differentiation toward neuronal phenotypes. Moreover, they suggest that the poor expansion of olfactory-spheres may be in part due to intrinsic properties of the olfactory epithelial stem/progenitor cell population.

Highlights

  • The olfactory epithelium is a neurogenic tissue comprising a population of olfactory receptor neurons that are renewed throughout adulthood by a population of stem and progenitor cells

  • In contrast to the subventricular zone (SVZ), hippocampus and the olfactory bulb, the olfactory epithelium represents an accessible source of stem/progenitor cells for autologous transplantation for central nervous system (CNS) repair that can be isolated by simple biopsy without profoundly altering the sense of smell [6,7]

  • These data suggest that the olfactory mucosa does not contain factors that are inhibitory to neural stem/progenitor cell proliferation but does contain factors that steer differentiation toward neuronal phenotypes

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Summary

Introduction

The olfactory epithelium is a neurogenic tissue comprising a population of olfactory receptor neurons that are renewed throughout adulthood by a population of stem and progenitor cells. Because of their relative accessibility compared to intra-cranially located neural stem/ progenitor cells, olfactory epithelium stem and progenitor cells make attractive candidates for autologous cell-based therapy. The olfactory epithelium is a neurogenic tissue containing a population of olfactory receptor neurons (ORNs) that are renewed throughout adulthood [1]. HBCs are relatively quiescent, but following injury and ORN degeneration they proliferate and can give rise to GBCs and non-neuronal lineage cells, and thereby regenerate the olfactory epithelium [4,5]. Few methods to expand olfactory stem and progenitor cells under serum-free conditions have been described and as a result, the therapeutic values of olfactory stem and progenitor cells remains uncertain

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