Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic rats
Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic rats
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DOI：
10.1097/01.tp.0000235532.00920.7a
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发表时间：
2006-10-15
期刊：
影响因子：
6.2
通讯作者：
Koliatsos, Vassilis E.
中科院分区：
文献类型：
--
作者：
Xu, Leyan;Yan, Jun;Koliatsos, Vassilis E.
背景神经系统退行性和创伤性疾病的实验疗法最近已经通过添加神经干细胞（NSC）作为用于细胞替代的胎儿组织的替代物而丰富。神经退行性疾病存在细胞死亡信号可能干扰移植细胞的活力的额外问题。成人脊髓提出了进一步的挑战，NSC分化，因为缺乏内在的发展潜力和负面的结果，一些先前的研究。将人胚胎脊髓神经干细胞移植到SD 1 G93 A大鼠的腰髓内。评估移植的NSC的分化命运及其对运动神经元数量、运动性能、疾病发作和存活趋势/寿命的影响。用分子和细胞学方法探讨了临床疗效的营养机制。人类神经干细胞广泛分化为神经元，与宿主神经细胞形成突触接触，并表达和释放胶质细胞系源性神经营养因子和脑源性神经营养因子。NSC移植物延迟了大鼠SOD 1 G93 A模型典型的暴发性运动神经元疾病的发作和进展，并将这些动物的寿命延长了10天以上，尽管限制性移植时间表仅限于腰椎突起。NSC移植物可以在神经退行性环境中存活良好，并发挥强大的临床作用;这些作用的至少一部分可能与这些移植物表达和释放运动神经元生长因子的能力有关，这些生长因子通过移植物-宿主连接递送至宿主运动神经元。
Background. Experimental therapeutics for degenerative and traumatic diseases of the nervous system have been recently enriched with the addition of neural stem cells (NSCs) as alternatives to fetal tissues for cell replacement. Neurodegenerative diseases present the additional problem that cell death signals may interfere with the viability of grafted cells. The adult spinal cord raises further challenges for NSC differentiation because of lack of intrinsic developmental potential and the negative outcomes of several prior attempts.Method. NSCs from human fetal spinal cord were grafted into the lumbar cord of SOD1 G93A rats. The differentiation fate of grafted NSCs and their effects on motor neuron number, locomotor performance, disease onset, and survival trends/longevity were assessed. Trophic mechanisms of observed clinical effects were explored with molecular and cellular methodologies.Result. Human NSCs showed extensive differentiation into neurons that formed synaptic contacts with host nerve cells and expressed and released glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. NSC grafts delayed the onset and progression of the fulminant motor neuron disease typical of the rat SOD1 G93A model and extended the lifespan of these animals by more than 10 days, despite the restricted grafting schedule that was limited to the lumbar protuberance.Conclusion. NSC grafts can survive well in a neurodegenerative environment and exert powerful clinical effects; at least a portion of these effects may be related to the ability of these grafts to express and release motor neuron growth factors delivered to host motor neurons via graft-host connections.