遗传性疾病“脊髓性肌萎缩”（SMA）是造成儿童死亡的最常见神经失调症状之一，由SMN1基因两个版本同时发生的突变引起。人们对SMA病理知之甚少，部分原因是，这种疾病是人类独有的，人类有该基因的两个版本——SMN1和 SMN2，而啮齿类和其他实验模型动物只有一个版本。
现在，研究人员已经设计出一种新方法，该方法能生成在细胞层次上研究SMA疾病病理的一种工具。来自一个患有SMA的儿童的皮肤成纤维细胞（同时为了对比也取了来自其未受该疾病影响的母亲的这种细胞）被用来生成“诱导的多能干细胞”（iPS）细胞系。它们形成神经前体细胞培养，该培养可产生保持该疾病表现型的分化的神经组织和运动神经元。该培养还对已知能提升与该疾病相关的突变蛋白水平的药物有反应。类似的iPS技术对于如亨廷顿疾病等其他遗传疾病的研究也许有使用价值。
Nature 457, 277-280 (15 January 2009) | doi:10.1038/nature07677
Induced pluripotent stem cells from a spinal muscular atrophy patient
Allison D. Ebert1,2, Junying Yu3, Ferrill F. Rose, Jr4, Virginia B. Mattis4, Christian L. Lorson4, James A. Thomson2,3,5 & Clive N. Svendsen1,2,5,6
1 The Waisman Center, and,
2 The Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, Wisconsin 53705, USA
3 The Genome Center and Wisconsin National Primate Research Center, University of Wisconsin-Madison, 425 Henry Mall, Madison, Wisconsin 53706, USA
4 Department of Veterinary Pathobiology, Bond Life Sciences Center, University of Missouri, 1201 Rollins Road, Columbia, Missouri 65211, USA
5 Department of Anatomy, University of Wisconsin-Madison, 1300 University Avenue Madison, Wisconsin 53706, USA
6 Department of Neurology, University of Wisconsin-Madison, 600 North Highland Avenue, Madison, Wisconsin 53792, USA
Spinal muscular atrophy is one of the most common inherited forms of neurological disease leading to infant mortality. Patients have selective loss of lower motor neurons resulting in muscle weakness, paralysis and often death. Although patient fibroblasts have been used extensively to study spinal muscular atrophy, motor neurons have a unique anatomy and physiology which may underlie their vulnerability to the disease process. Here we report the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy. These cells expanded robustly in culture, maintained the disease genotype and generated motor neurons that showed selective deficits compared to those derived from the child's unaffected mother. This is the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen new drug compounds and develop new therapies.
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