P22: In vitro characterization and assessment of differentiation potential of adult rat olfactory neuroepithelium derived neural stem cells

In this study we examine the differentiating potential of adult peripheral neural stem cells whose accessibility might favour their use in transplant-mediated repair over adult CNS-derived stem cells. Olfactory neuroepithelial stem cells (ONSC) can be isolated as EGF- and FGF-2-responding neurospheres similar to those obtained from adult brain. Using RT-PCR we demonstrated that rat ONSC neurospheres express transcription factors in common with both neural crest cells and SVZ neurospheres when cultured in these conditions. Although ONSCs are normally committed to generate mainly olfactory neurons, in this study we examined whether ONSCs can be modified by various culture conditions to derive both glial cells and neurons. We found that neurosphere-forming ONSCs plated on laminin generated more β-tubulin(–)/diffuse GFAP-immunoreactive cells (23.1%) than β-tubulin(+)/GFAP(–) cells (3.9%) in the presence of BMP7 and CNTF. When treated with the combination of retinoic acid and NT3, the spheres preferentially produced,-tubulin(+)/GFAP(–) cells (26.6%) over β-tubulin(–)/diffuse GFAP-immunoreactive cells (6%). These results indicate that ONSCs can be induced in vitro to differentiate into both neurons and glia, opening up the possibility of deriving specific neuronal or glial phenotypes for cell based therapies of traumatic or neurodegenerative disease.