Secreted factors from olfactory mucosa cells expanded as free-floating spheres increase neurogenesis in olfactory bulb neurosphere cultures.
BACKGROUND
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. 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.


RESULTS
In 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.


CONCLUSIONS
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. 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.
Barraud
Perrine
P
Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK. pb379@cam.ac.uk
He
Xiaoling
X
Caldwell
Maeve A
MA
Franklin
Robin Jm
RJ
D000818:Animals; D000831:Animals, Newborn; D064032:Calbindin 2; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; D007150:Immunohistochemistry; D051379:Mice; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020890:Neuregulin-1; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology*; D009831:Olfactory Mucosa / Q000378:metabolism*; D010641:Phenotype; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D018874:Spheroids, Cellular; D013234:Stem Cells / Q000166:cytology*; D014404:Tubulin / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D064032:Calbindin 2; D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D064030:S100 Calcium Binding Protein G; D014404:Tubulin; C528900:glial fibrillary astrocytic protein, mouse; D005680:gamma-Aminobutyric Acid