新华社东京5月9日电 （记者蓝建中）日本京都大学一个研究小组在美国《干细胞转化医学》杂志上发表论文说，他们利用人类胚胎干细胞成功制作出具有肌萎缩侧索硬化症（渐冻症）特征的细胞，这将有助于弄清该病的机制并开发治疗药物。
肌萎缩侧索硬化症俗称渐冻症，是由于运动神经出现障碍，导致全身肌肉逐渐变得无力的一种疾病。渐冻症患者约有10％属于遗传性患病。由于不清楚详细的致病原因，医学界一直没有找到根治此病的方法。
在遗传性渐冻症患者中，约有20％是由于“SOD1”基因变异所致。研究小组将变异“SOD1”基因导入人类胚胎干细胞，使其分化成运动神经细胞等。结果在这些分化后的运动神经细胞中再现了渐冻症患者细胞的一些形状、性质特征，比如神经突形状大小多变、细胞易坏死等。
研究小组负责人中辻宪夫说，有报告显示，非遗传性的渐冻症也与“SOD1”基因有关，期待本次开发的细胞模型在渐冻症治疗中发挥重大作用。(生物谷：Bioon.com)
doi: 10.5966/sctm.2011-0061
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Amyotrophic Lateral Sclerosis Model Derived from Human Embryonic Stem Cells Overexpressing Mutant Superoxide Dismutase 1
Tamaki Wadaa, Sravan K. Goparajub, Norie Tooib, Haruhisa Inouec, Ryosuke Takahashid, Norio Nakatsujib,e and Kazuhiro Aibaa,b
The generation of amyotrophic lateral sclerosis (ALS) disease models is an important subject for investigating disease mechanisms and pharmaceutical applications. In transgenic mice, expression of a mutant form of superoxide dismutase 1 (SOD1) can lead to the development of ALS that closely mimics the familial type of ALS (FALS). Although SOD1 mutant mice show phenotypes similar to FALS, dissimilar drug responses and size differences limit their usefulness to study the disease mechanism(s) and identify potential therapeutic compounds. Development of an in vitro model system for ALS is expected to help in obtaining novel insights into disease mechanisms and discovery of therapeutics. We report the establishment of an in vitro FALS model from human embryonic stem cells overexpressing either a wild-type (WT) or a mutant SOD1 (G93A) gene and the evaluation of the phenotypes and survival of the spinal motor neurons (sMNs), which are the neurons affected in ALS patients. The in vitro FALS model that we developed mimics the in vivo human ALS disease in terms of the following: (a) selective degeneration of sMNs expressing the G93A SOD1 but not those expressing the WT gene; (b) susceptibility of G93A SOD1-derived sMNs to form ubiquitinated inclusions; (c) astrocyte-derived factor(s) in the selective degeneration of G93A SOD1 sMNs; and (d) cell-autonomous, as well as non-cell-autonomous, dependent sMN degeneration. Thus, this model is expected to help unravel the disease mechanisms involved in the development of FALS and also lead to potential drug discoveries based on the prevention of neurodegeneration.
