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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Human embryonic germ cell derivatives facilitate motor recovery of rats with diffuse motor neuron injury.
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Human embryonic germ cell derivatives facilitate motor recovery of rats with diffuse motor neuron injury.

机译：人类胚胎生殖细胞衍生物可促进运动神经元损伤大鼠的运动恢复。

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摘要

We have investigated the potential of human pluripotent cells to restore function in rats paralyzed with a virus-induced motor neuronopathy. Cells derived from embryonic germ cells, termed embryoid body-derived (EBD) cells, introduced into the CSF were distributed extensively over the rostrocaudal length of the spinal cord and migrated into the spinal cord parenchyma in paralyzed, but not uninjured, animals. Some of the transplanted human cells expressed the neuroglial progenitor marker nestin, whereas others expressed immunohistochemical markers characteristic of astrocytes or mature neurons. Rare transplanted cells developed immunoreactivity to choline acetyltransferase (ChAT) and sent axons into the sciatic nerve as detected by retrograde labeling. Paralyzed animals transplanted with EBD cells partially recovered motor function 12 and 24 weeks after transplantation, whereas control animals remained paralyzed. Semi-quantitative analysis revealed that the efficiency of neuronal differentiation and extension of neurites could not account for the functional recovery. Rather, transplanted EBD cells protected host neurons from death and facilitated reafferentation of motor neuron cell bodies. In vitro, EBD cells secrete transforming growth factor-alpha (TGF-alpha) and brain-derived neurotrophic factor (BDNF). Neutralizing antibodies to TGF-alpha and to BDNF abrogated the ability of EBD-conditioned media to sustain motor neuron survival in culture, whereas neutralizing antibodies to BDNF eliminated the axonal outgrowth from spinal organotypics observed with direct coculture of EBD cells. We conclude that cells derived from human pluripotent stem cells have the capacity to restore neurologic function in animals with diffuse motor neuron disease via enhancement of host neuron survival and function.
机译：我们已经研究了人类多能细胞在被病毒诱导的运动神经病瘫痪的大鼠中恢复功能的潜力。引入CSF的源自胚胎生殖细胞的细胞（称为胚状体衍生（EBD）细胞）广泛分布在脊髓的后尾巴长度上，并在瘫痪但未受伤的动物中迁移到脊髓实质中。某些移植的人类细胞表达了神经胶质祖细胞标记物巢蛋白，而另一些表达了星形胶质细胞或成熟神经元的免疫组织化学标记物。稀有移植细胞对胆碱乙酰转移酶（ChAT）产生免疫反应，并通过逆行标记检测出轴突进入坐骨神经。移植了EBD细胞的瘫痪动物在移植后12和24周部分恢复了运动功能，而对照动物仍然处于瘫痪状态。半定量分析表明，神经元分化和神经突扩展的效率不能解释功能恢复。相反，移植的EBD细胞可保护宿主神经元免于死亡，并促进运动神经元细胞体的转运。在体外，EBD细胞分泌转化生长因子-α（TGF-alpha）和脑源性神经营养因子（BDNF）。对TGF-α和BDNF的中和抗体消除了EBD条件培养基在培养中维持运动神经元存活的能力，而对BDNF的中和抗体消除了由EBD细胞直接共培养观察到的脊髓器官型轴突生长。我们得出的结论是，源自人类多能干细胞的细胞具有通过增强宿主神经元存活和功能来恢复弥漫性运动神经元疾病动物神经功能的能力。

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