Moyse Emmanuel, Segura Stéphanie, Liard Oliver, Mahaut Stéphanie, Mechawar Naguib
Laboratoire Physiologie Neurovégétative, UMR 6231 CNRS, Université Aix-Marseille-3, Av. Escadrille Normandie-Niemen, 13397 Marseille, France.
Curr Stem Cell Res Ther. 2008 Sep;3(3):163-84. doi: 10.2174/157488808785740334.
The discovery of neural stem cells (NSC) which ensure continuous neurogenesis in the adult mammalian brain, has led to a conceptual revolution in basic neuroscience and to high hopes for clinical nervous tissue repair. However, several research issues remain to address before neural stem cells can be harnessed for regenerative therapies. The presence of NSC in a nervous structure is demonstrated in vitro by primary culture of dissociated adult nervous tissue in the presence of the specific mitogens EGF and bFGF. This leads to spherical masses of proliferating cells endowed with capacities for self-renewal and, after growth factor removal, differentiation into the three characteristic cell types of nervous tissue (neurons, astrocytes, oligodendrocytes). In vivo, neurogenesis per se, i.e. production of new neurons, occurs only in a small subset of NSC-endowed structures. The production of oligodendrocytes, i.e. myelinating glial cells, is similarly restricted. Such in vivo restrictions were formally demonstrated to arise from the tissular microenvironnement, which led to the emerging concept of "neurogenic niche". In this context, major challenges now consist in identifying the nature of tissue-specific extracellular signals that determine lineage commitment of NSC progeny, understanding why NSCs display weak in vivo reactivity to lesions compared to other stem cell types in adults, and identifying the factors behind the very high resistance to tumorigenesis displayed by NSCs. Altogether, the current data offer hope for the future use of adult NSCs in regenerative therapies, provided that tissue-specific signals are identified in view of counteracting the intrinsic repression of new cell genesis and/or stimulating endogenous NSC recruitment to lesion sites.
神经干细胞（NSC）的发现确保了成年哺乳动物大脑中神经发生的持续进行，这在基础神经科学领域引发了一场概念革命，并为临床神经组织修复带来了很高的期望。然而，在神经干细胞可用于再生治疗之前，仍有几个研究问题有待解决。在体外，通过在特定有丝分裂原表皮生长因子（EGF）和碱性成纤维细胞生长因子（bFGF）存在的情况下对成年神经组织进行原代培养，可证明神经干细胞在神经结构中的存在。这会导致形成增殖细胞的球形团块，这些细胞具有自我更新能力，并且在去除生长因子后，可分化为神经组织的三种特征性细胞类型（神经元、星形胶质细胞、少突胶质细胞）。在体内，神经发生本身，即新神经元的产生，仅发生在少数具有神经干细胞的结构中。少突胶质细胞（即形成髓鞘的神经胶质细胞）的产生同样受到限制。这种体内限制已被正式证明是由组织微环境引起的，这导致了“神经发生微环境”这一新兴概念的出现。在这种背景下，目前的主要挑战在于确定决定神经干细胞后代谱系定向的组织特异性细胞外信号的性质，理解为什么与成体中的其他干细胞类型相比，神经干细胞对损伤的体内反应较弱，以及确定神经干细胞对肿瘤发生具有极高抗性背后的因素。总体而言，目前的数据为未来在再生治疗中使用成年神经干细胞带来了希望，前提是鉴于抵消新细胞生成的内在抑制和/或刺激内源性神经干细胞募集到损伤部位来确定组织特异性信号。
