REVIEW ARTILCE: Cell therapy and stem cells in animal models of motor neuron disorders

REVIEW ARTILCE: Cell therapy and stem cells in animal models of motor neuron disorders
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综述文章:运动神经元疾病动物模型中的细胞疗法和干细胞

DOI:
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发表时间:
2007
影响因子:
3.4
通讯作者:
O. Isacson
O. Isacson
中科院分区:
医学3区
文献类型:
--
作者:
E. Hedlund;M. Hefferan;M. Marsala;O. Isacson

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肌萎缩性侧索硬化症(ALS)、脊髓延髓肌萎缩症(或肯尼迪病)、脊髓性肌萎缩症和脊髓性肌萎缩症伴呼吸窘迫1是主要影响运动神经元的神经退行性疾病,目前缺乏有效的治疗方法。最近在ALS的动物模型以及原代和胚胎干细胞模型中的研究,利用突变形式的Cu/Zn超氧化物歧化酶1的过表达,表明这些模型中的运动神经元变性部分是非细胞自主事件,并且通过提供遗传上未受损的支持细胞,如小胶质细胞或生长因子分泌细胞,可以延迟发作并增加存活率。使用急性运动神经元损伤的模型,已经表明植入脊髓中的胚胎干细胞衍生的运动神经元可以支配肌肉靶点并改善功能恢复。因此,在运动神经元疾病中开发旨在保护和/或替代丢失的运动神经元、中间神经元以及非神经元细胞的细胞疗法存在基本原理。这篇综述评估了运动神经元疾病动物模型中使用的方法及其治疗意义。
Amyotrophic lateral sclerosis (ALS), spinal bulbar muscular atrophy (or Kennedy's disease), spinal muscular atrophy and spinal muscular atrophy with respiratory distress 1 are neurodegenerative disorders mainly affecting motor neurons and which currently lack effective therapies. Recent studies in animal models as well as primary and embryonic stem cell models of ALS, utilizing over‐expression of mutated forms of Cu/Zn superoxide dismutase 1, have shown that motor neuron degeneration in these models is in part a non cell‐autonomous event and that by providing genetically non‐compromised supporting cells such as microglia or growth factor‐excreting cells, onset can be delayed and survival increased. Using models of acute motor neuron injury it has been shown that embryonic stem cell‐derived motor neurons implanted into the spinal cord can innervate muscle targets and improve functional recovery. Thus, a rationale exists for the development of cell therapies in motor neuron diseases aimed at either protecting and/or replacing lost motor neurons, interneurons as well as non‐neuronal cells. This review evaluates approaches used in animal models of motor neuron disorders and their therapeutic relevance.
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