Barraud Perrine, He Xiaoling, Caldwell Maeve A, Franklin Robin Jm
Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
BMC Neurosci. 2008 Feb 18;9:24. doi: 10.1186/1471-2202-9-24.
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.
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.
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.
嗅觉上皮是一种神经发生组织，由一群嗅觉受体神经元组成，这些神经元在成年期通过一群干细胞和祖细胞不断更新。与位于颅内的神经干细胞/祖细胞相比，嗅觉上皮干细胞和祖细胞相对易于获取，这使其成为基于自体细胞治疗的有吸引力的候选者。然而，在神经球分析中，当在生长因子刺激下作为自由漂浮球体（嗅觉球）生长时，嗅觉干细胞和祖细胞的扩增非常缓慢。
为了研究嗅觉黏膜细胞是否对未成熟神经细胞的增殖和/或分化有外在调节作用，我们在由嗅觉黏膜来源的球体（嗅觉球）条件培养基存在的情况下，培养了从小鼠新生嗅球或脑室下区（SVZ）衍生的神经祖细胞。我们的数据表明，与对照培养基相比，嗅觉黏膜细胞产生的可溶性因子会影响嗅球神经祖细胞的分化，但不影响其增殖。此外，嗅觉黏膜衍生的可溶性因子增加了神经发生，尤其有利于非GABA能神经元的生成。嗅觉黏膜条件培养基还含有几种具有神经营养/神经保护特性的因子。嗅觉球条件培养基不影响SVZ衍生神经祖细胞的增殖或分化。
这些数据表明，嗅觉黏膜不含抑制神经干细胞/祖细胞增殖的因子，但含有引导分化为神经元表型的因子。此外，它们表明嗅觉球扩增不佳可能部分归因于嗅觉上皮干细胞/祖细胞群体的内在特性。
