目前，缺乏合适的研究模型是科学家们研究唐氏综合征面临的最大挑战之一，现有的动物模型和细胞系模型在模拟人类疾病方面有很大的局限性，研究结果并不能很好地转化到病人群体。幸运的是，用干细胞作为研究工具可以弥补这一缺陷，因为它可以直接将病人自体细胞诱导为各种细胞类型来支持研究。但是干细胞的收集过程比较复杂且具有侵入性，对象为儿童或者存在智力障碍的病人时难以通过相关审核。

　　日前，来自凯斯西储大学医学院的研究人员首次实现了直接从尿液中收集细胞并将其诱导成用于唐氏综合征研究的干细胞，克服了之前收集干细胞需要面对的伦理挑战。“我们首次利用唐氏综合征病人尿液中的细胞构建诱导多能干细胞，未来可以用这种方法筛选能够改善唐氏综合征病人生命质量的新药物。”文章作者Alberto Costa教授这样说道。

　　研究人员从尿液样本中提取了可能源自肾脏上皮组织的上皮细胞，通过无累加游离基因载体技术成功构造诱导干细胞（T21-iPSCs），且经过20代次后依然能保持T21染色体稳定性，其蛋白毒性敏感性也优于整倍体iPSCs。另外，T21-iPSCs也表现出比皮肤活检组织诱导干细胞更稳定的细胞状态，这可能是因为皮肤细胞经常暴露于阳光下存在DNA损伤，而利用这种新方法生成的干细胞不存在这样的情况。该研究还表明获得的T21-iPSCs可以分化成与唐氏综合征研究相关的多种细胞类型，如神经元和心肌细胞。总的来说，这种新模型提供了一种伦理健全、临床相关并且可高度转化的方法用于研究唐氏综合征。

推荐阅读原文：

Generation of Integration-Free Induced Pluripotent Stem Cells from Urine-Derived Cells Isolated from Individuals with Down Syndrome.

Down syndrome (DS) is a genetic disorder caused by trisomy 21 (T21). Over the past two decades, the use of mouse models has led to significant advances in the understanding of mechanisms underlying various phenotypic features and comorbidities secondary to T21 and even informed the design of clinical trials aimed at enhancing the cognitive abilities of persons with DS. In spite of its success, this approach has been plagued by all the typical limitations of rodent modeling of human disorders and diseases. Recently, several laboratories have succeeded in producing T21 human induced pluripotent stem cells (T21-iPSCs) from individuals with DS, which is emerging as a promising complementary tool for the study of DS. Here, we describe the method by which we generated 10 T21-iPSC lines from epithelial cells in urine samples, presumably from kidney epithelial origin, using nonintegrating episomal vectors. We also show that these iPSCs maintain chromosomal stability for well over 20 passages and are more sensitive to proteotoxic stress than euploid iPSCs. Furthermore, these iPSC lines can be differentiated into glutamatergic neurons and cardiomyocytes. By culturing urine-derived cells and maximizing the efficiency of episomal vector transfection, we have been able to generate iPSCs noninvasively and effectively from participants with DS in an ongoing clinical trial, and thus address most shortcomings of previously generated T21-iPSC lines. These techniques should extend the application of iPSCs in modeling DS and other neurodevelopmental and neurodegenerative disorders, and may lead to future human cell-based platforms for high-throughput drug screening.