Université Pierre et Marie Curie-Paris 6, UMR S 975, Paris, France.
J Neurosci Res. 2009 Nov 15;87(15):3438-46. doi: 10.1002/jnr.22194.
Multipotential neural stem/precursor cells of the central nervous system were extensively studied for their properties of generating myelinating oligodendrocytes both in vitro and in vivo upon engraftment in animal models of myelin disorders, such as leucodystrophy and multiple sclerosis. These studies provided proof-of-principle that efficient myelination can be achieved by cell transplantation. However, one major drawback of cell-based therapy of myelin diseases is the difficulty in generating oligodendrocytes efficiently from human fetal neural stem/precursor cells (hNPC). Here we explored whether overexpression of the basic helix-loop-helix (bHLH) transcription factor Olig2 in fetal hNPC could enhance the generation of oligodendrocytes both in vitro and in vivo. We report that transduction of hNPC with Olig2-encoding lentiviral vectors enhances their commitment toward an oligodendroglial fate. Moreover, Olig2-transduced hNPC, grafted into the dysmyelinated shiverer mouse brain, survived up to 9 weeks, migrated extensively, and differentiated into MBP(+) myelinating oligodendrocytes. In contrast, control hNPC remained at a less mature stage and generated very few myelinating oligodendrocytes. Our study indicates that bHLH transcription factors, such as Olig2, are interesting targets for directing hNPC into myelinating oligodendrocytes.
中枢神经系统的多潜能神经干细胞/前体细胞在体外和体内动物髓鞘疾病模型（如白质营养不良和多发性硬化症）中移植后，因其生成髓鞘形成少突胶质细胞的特性而得到广泛研究。这些研究证明通过细胞移植可以实现有效的髓鞘形成。然而，髓鞘疾病的细胞治疗的一个主要缺点是难以从人胎儿神经干细胞/前体细胞（hNPC）中有效地产生少突胶质细胞。在这里，我们探讨了在胎儿 hNPC 中过表达碱性螺旋-环-螺旋（bHLH）转录因子 Olig2 是否可以增强体外和体内少突胶质细胞的生成。我们报告说，用编码 Olig2 的慢病毒载体转导 hNPC 可以增强其向少突胶质细胞命运的定向。此外，转导 Olig2 的 hNPC 移植到脱髓鞘的颤抖鼠脑内，可存活长达 9 周，广泛迁移并分化为 MBP（+）髓鞘形成少突胶质细胞。相比之下，对照 hNPC 仍处于较不成熟的阶段，产生的髓鞘形成少突胶质细胞很少。我们的研究表明，bHLH 转录因子，如 Olig2，是将 hNPC 定向为髓鞘形成少突胶质细胞的有趣靶标。
