来自澳大利亚生物工程与纳米技术研究所(Australian Institute for Bioengineering and Nanotechnology, AIBN)的研究人员在理解和治疗一种被称作共济失调性毛细血管扩张症(ataxia-telangiectasia, AT)的退化性疾病的目标上更接近一步。
澳大利亚生物工程与米技术研究所副教授 Ernst Wolvetang领导的研究小组与来自澳大利亚昆士兰医学研究所(Queensland Institute of Medical Research, QIMR)和昆士兰大学临床研究中心(University of Queensland's Centre for Clinical Research, UQCCR)的研究人员合作开展研究，并且是第一次将来自患有AT的病人身上的皮肤细胞重编程为诱导性多能干细胞(induced pluripotent stem cells,iPSCs)，这样他们能够研究潜在治疗方法的有效性。
这种重编程过程涉及提取皮肤细胞，产生多能性干细胞，然后诱导它们变成脑细胞以便用于实验室研究。
患有AT的病人容易患上癌症和大脑退化性疾病，这是因为在他们体内一个用来识别和修复DNA损伤的基因存在缺陷。
副教授Wolvetang说，将来自患有AT的儿童的皮肤细胞进行重编程的能力为人们提供一种可以自我更新的细胞来源来研究这种神经退化性疾病和找到治疗它的药物。
副教授Wolvetang说，“下一步就是校正源自这些病人的诱导性多能干细胞(iPSCs)中的基因突变，然后将这些经过校正的干细胞转化为脑细胞和血细胞，并且还要证实它们能够替换导致这种疾病产生的缺陷性细胞。移植这些经过校正的细胞(仍然需要多年才可能实现)或者利用这项研究中产生的细胞而开发出的药物可能有助于治疗这种疾病。”
研究人员有望在一到两年内开始药物筛选，但是动物测试必须在它们能够用于人类治疗之前完成。
共济失调性毛细血管扩张症(AT)是一种罕见的遗传性疾病，它导致严重性残疾，包括运动和协调存在困难，免疫系统受到削弱。患有AT的病人很容易遭受感染，而且患上癌症的风险不断增加。它的发病率在1/300000到1/100000。患有这种疾病的病人在十几岁初期就经常坐在轮椅上，而且当他们到达二十多岁时，它是致命性的。
研究人员将他们的研究成果发表在Stem Cells Translational Medicine期刊上。(生物谷：Bioon.com)
doi:10.5966/sctm.2012-0024
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Induced Pluripotent Stem Cells from Ataxia-Telangiectasia Recapitulate the Cellular Phenotype
Sam Naylera,b, Magtouf Gateib, Sergei Kozlovb, Richard Gattic, Jessica C. Mard, Christine A. Wellsa, Martin Lavinb,e and Ernst Wolvetang
Pluripotent stem cells can differentiate into every cell type of the human body. Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) therefore provides an opportunity to gain insight into the molecular and cellular basis of disease. Because the cellular DNA damage response poses a barrier to reprogramming, generation of iPSCs from patients with chromosomal instability syndromes has thus far proven to be difficult. Here we demonstrate that fibroblasts from patients with ataxia-telangiectasia (A-T), a disorder characterized by chromosomal instability, progressive neurodegeneration, high risk of cancer, and immunodeficiency, can be reprogrammed to bona fide iPSCs, albeit at a reduced efficiency. A-T iPSCs display defective radiation-induced signaling, radiosensitivity, and cell cycle checkpoint defects. Bioinformatic analysis of gene expression in the A-T iPSCs identifies abnormalities in DNA damage signaling pathways, as well as changes in mitochondrial and pentose phosphate pathways. A-T iPSCs can be differentiated into functional neurons and thus represent a suitable model system to investigate A-T-associated neurodegeneration. Collectively, our data show that iPSCs can be generated from a chromosomal instability syndrome and that these cells can be used to discover early developmental consequences of ATM deficiency, such as altered mitochondrial function, that may be relevant to A-T pathogenesis and amenable to therapeutic intervention.
