Zangiacomi Vincent, Balon Norbert, Maddens Stéphane, Lapierre Valérie, Tiberghien Pierre, Schlichter Remy, Versaux-Botteri Claudine, Deschaseaux Frédéric
Neurogenèse et Processus Intégratifs dans l'Olfaction, Laboratoire de Neurosciences, Université de Franche-Comté, Besançon, France.
Stem Cells Dev. 2008 Oct;17(5):1005-16. doi: 10.1089/scd.2007.0248.
Previous studies described that neurons could be generated in vitro from human umbilical cord blood cells. However, there are few data concerning their origin. Notably, cells generating neurons are not well characterized. The present study deals with the origin of cord blood cells generating neurons and mechanisms allowing the neuronal differentiation. We studied neuronal markers of both total fractions of cord blood and stem/progenitor cord blood cells before and after selections and cultures. We also compared neuronal commitment of cord blood cells to that observed for the neuronal cell line SK-N-BE(2). Before cultures, neuronal markers are found within the total fraction of cord blood cells. In CD133+ stem/progenitor cell fraction only immature neuronal markers are detected. However, CD133+ cells are unable to give rise to neurons in cultures, whereas this is achieved when total fraction of cord blood cells is used. In fact, mature functional neurons can be generated from CD133+ cells only in cell-to-cell close contact with either CD133- fraction or a neurogenic epithelium. Furthermore, since CD133+ fraction is heterogenous, we used several selections to precisely identify the phenotype of cord blood-derived neuronal stem/progenitor cells. Results reveal that only CD34- cells from CD133+ fraction possess neuronal potential. These data show the phenotype of cord blood neuronal stem/progenitor cells and the crucial role of direct cell-to-cell contact to achieve their commitment. Identifying the neuron supporting factors may be beneficial to the use of cord blood neuronal stem/progenitor cells for regenerative medicine.
先前的研究表明,人脐带血细胞可在体外生成神经元。然而,关于它们的起源的数据却很少。值得注意的是,生成神经元的细胞尚未得到很好的表征。本研究探讨了脐带血细胞生成神经元的起源以及允许神经元分化的机制。我们研究了脐带血总细胞组分以及经分选和培养前后的脐带血干细胞/祖细胞的神经元标志物。我们还将脐带血细胞的神经元定向分化与神经母细胞瘤细胞系SK-N-BE(2)的情况进行了比较。在培养之前,在脐带血细胞的总组分中发现了神经元标志物。在CD133+干细胞/祖细胞组分中,仅检测到未成熟的神经元标志物。然而,CD133+细胞在培养中无法产生神经元,而使用脐带血细胞总组分时则可以。实际上,只有当CD133+细胞与CD133-组分或神经发生上皮细胞进行细胞间紧密接触时,才能从CD133+细胞生成成熟的功能性神经元。此外,由于CD133+组分是异质性的,我们采用了几种分选方法来精确鉴定脐带血来源的神经元干细胞/祖细胞的表型。结果显示,只有CD133+组分中的CD34-细胞具有神经元潜能。这些数据揭示了脐带血神经元干细胞/祖细胞的表型以及细胞间直接接触对其定向分化的关键作用。确定神经元支持因子可能有助于将脐带血神经元干细胞/祖细胞用于再生医学。