PNAS:新研究带来脊髓损伤修复的希望
2017/05/01
4月24日PNAS上在线发表了美国Gladstone研究所科学家的新发现:他们通过干细胞生产出V2a的中间神经元,为修复脊髓损伤提供新的希望。当这些细胞移植到小鼠脊髓时,中间神经元能出芽并与现存细胞整合在一起。


美国Gladstone研究所的科学家Todd McDevitt博士和他的团队发现一种特殊类型的干细胞可以为修复脊髓损伤提供新的希望。这些细胞是被称为V2a的中间神经元,在脊髓发出信号帮助控制运动。当研究人员将这些细胞移植到小鼠脊髓时,中间神经元能出芽并与现存细胞整合在一起。相关文章于4月24日在线发表在PNAS上。

重建V2a中间神经元是脊髓损伤修复的关键

V2a的中间神经元将大脑的信号传递到脊髓,在脊髓和运动神经元连接,传递到胳膊和腿。中间神经元能长距离覆盖,协调肌肉运动包括呼吸。

对V2a的中间神经元的伤害会损害大脑和四肢之间的连接,造成脊髓损伤的瘫痪。


第一作者Jessica Butts说:“我们的主要挑战是找到合适的时机和信号分子恰当的浓度,来生产V2a中间神经元而不是其它细胞类型。我们利用我们对脊髓发育所了解的知识,来鉴定正确的化合物组合,并优化我们的程序获得最多的V2a中间神经元。”

研究人员将V2a中间神经元移植到健康小鼠的脊髓。在新的环境中,细胞适当成熟并与现有的脊髓细胞相结合。重要的是,中间神经元移植后的小鼠能正常行动,并没有表现出损害的迹象。研究人员介绍移植的细胞在两个方向上都能长距离地出芽,这是V2a中间神经元的特征,之后并能与宿主的神经元相连接。

研究人员说他们下一步是将细胞移植到脊髓损伤的小鼠,看V2a中间神经元是否能够在损伤发生后帮助恢复运动能力。他们也有兴趣探索这些细胞在神经退行性疾病,如淀粉样蛋白脊髓侧索硬化症中的潜在作用。

参考资料

Differentiation of V2a interneurons from human pluripotent stem cells

Discovery offers new hope to repair spinal cord injuries

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  • Differentiation of V2a interneurons from human pluripotent stem cells

    The spinal cord consists of multiple neuronal cell types that are critical to motor control and arise from distinct progenitor domains in the developing neural tube. Excitatory V2a interneurons in particular are an integral component of central pattern generators that control respiration and locomotion; however, the lack of a robust source of human V2a interneurons limits the ability to molecularly profile these cells and examine their therapeutic potential to treat spinal cord injury (SCI). Here, we report the directed differentiation of CHX10+ V2a interneurons from human pluripotent stem cells (hPSCs). Signaling pathways (retinoic acid, sonic hedgehog, and Notch) that pattern the neural tube were sequentially perturbed to identify an optimized combination of small molecules that yielded ∼25% CHX10+ cells in four hPSC lines. Differentiated cultures expressed much higher levels of V2a phenotypic markers (CHX10 and SOX14) than other neural lineage markers. Over time, CHX10+ cells expressed neuronal markers [neurofilament, NeuN, and vesicular glutamate transporter 2 (VGlut2)], and cultures exhibited increased action potential frequency. Single-cell RNAseq analysis confirmed CHX10+ cells within the differentiated population, which consisted primarily of neurons with some glial and neural progenitor cells. At 2 wk after transplantation into the spinal cord of mice, hPSC-derived V2a cultures survived at the site of injection, coexpressed NeuN and VGlut2, extended neurites >5 mm, and formed putative synapses with host neurons. These results provide a description of V2a interneurons differentiated from hPSCs that may be used to model central nervous system development and serve as a potential cell therapy for SCI.

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