美国科学家使用一个患有脊髓性肌萎缩症(SMA)儿童的皮肤细胞,制造了诱导多能干细胞(iPS细胞),利用这些iPS细胞培育出包含导致SMA疾病遗传缺陷的运动神经细胞,以观察该疾病怎样发展,并试图找到治疗该疾病的方法。发表在12月21日《自然》杂志上的该项研究,朝着利用iPS细胞来治疗疾病的目标又迈出了重要的一步。
美国威斯康辛大学麦迪逊分校的克莱夫·斯文德森团队使用一个患有SMA的儿童的皮肤细胞制造了iPS细胞,iPS在能够发育为任何器官或组织的能力上与胚胎干细胞类似。然后,研究人员诱导这些细胞变成运动神经细胞,因为身体内的每个细胞包含同样的遗传指令,使用这个儿童的皮肤细胞制造的运动神经细胞也携带该遗传疾病。同时,研究团队也使用该儿童健康母亲的细胞制造了运动神经细胞。
利用该儿童皮肤制造的运动神经细胞在2个月后开始死亡,而利用其母亲细胞制造的神经细胞则正常生长。由于iPS细胞能在实验室里生长几个月甚至几年,因此该实验可多次重复进行。斯文德森将其比作汽车事故的视频,可以反复播放,并找到原因。斯文德森说,该发现可使制药者对潜在的治疗方案进行测试以预防SMA中的神经死亡。
斯文德森实验室并非使用iPS细胞作为研究疾病新型工具的第一家。今年7月底,哈佛干细胞研究所的凯文·埃根使用患有肌萎缩性侧索硬化症的病人的皮肤细胞制造了iPS细胞,这是第一次将来自慢性病患者的皮肤细胞重组为iPS细胞,然后再诱变成理解和治疗疾病所需的特殊细胞类型。
SMA是一种遗传疾病,它会攻击脊髓中的运动神经细胞,人体内缺乏SMN蛋白(SMN蛋白是运动神经元生存蛋白,能够使肌肉活动)时会引发该疾病。患有该疾病的婴儿出生6个月后,该疾病就会慢慢发展,接着肌肉出现萎缩,无法控制运动,直至完全瘫痪,2岁左右就会死亡。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature,doi:10.1038/nature07677,Allison D. Ebert,Clive N. Svendsen
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.