Brigida Anna Lisa, Siniscalco Dario
Department of Experimental Medicine, Second University of Naples, 80138 Napoli, Italy.
J Stem Cells Regen Med. 2016 Nov 29;12(2):54-60. doi: 10.46582/jsrm.1202009. eCollection 2016.
Down Syndrome (DS), or Trisomy 21 Syndrome, is one of the most common genetic diseases. It is a chromosomal abnormality caused by a duplication of chromosome 21. DS patients show the presence of a third copy (or a partial third copy) of chromosome 21 (trisomy), as result of meiotic errors. These patients suffer of many health problems, such as intellectual disability, congenital heart disease, duodenal stenosis, Alzheimer's disease, leukemia, immune system deficiencies, muscle hypotonia and motor disorders. About one in 1000 babies born each year are affected by DS. Alterations in the dosage of genes located on chromosome 21 (also called HSA21) are responsible for the DS phenotype. However, the molecular pathogenic mechanisms of DS triggering are still not understood; newest evidences suggest the involvement of epigenetic mechanisms. For obvious ethical reasons, studies performed on DS patients, as well as on human trisomic tissues are limited. Some authors have proposed mouse models of this syndrome. However, not all the features of the syndrome are represented. Stem cells are considered the future of molecular and regenerative medicine. Several types of stem cells could provide a valid approach to offer a potential treatment for some untreatable human diseases. Stem cells also represent a valid system to develop new cell-based drugs and/or a model to study molecular disease pathways. Among stem cell types, patient-derived induced pluripotent stem (iPS) cells offer some advantages for cell and tissue replacement, engineering and studying: self-renewal capacity, pluripotency and ease of accessibility to donor tissues. These cells can be reprogrammed into completely different cellular types. They are derived from adult somatic cells via reprogramming with ectopic expression of four transcription factors (Oct3/4, Sox2, c-Myc and Klf4; or, Oct3/4, Sox2, Nanog, and Lin28). By reprogramming cells from DS patients, it is possible to obtain new tissue with the same genetic background, offering a valuable tool for studying this genetic disease and to design customized patient-specific stem cell therapies.
唐氏综合征（DS），即21三体综合征，是最常见的遗传疾病之一。它是由21号染色体重复导致的染色体异常。由于减数分裂错误，DS患者表现出21号染色体有第三个拷贝（或部分第三个拷贝）（三体性）。这些患者患有许多健康问题，如智力残疾、先天性心脏病、十二指肠狭窄、阿尔茨海默病、白血病、免疫系统缺陷、肌张力减退和运动障碍。每年出生的婴儿中约有千分之一受DS影响。位于21号染色体（也称为HSA21）上的基因剂量改变是DS表型的原因。然而，DS引发的分子致病机制仍不清楚；最新证据表明表观遗传机制参与其中。出于明显的伦理原因，对DS患者以及人类三体组织进行的研究有限。一些作者提出了该综合征的小鼠模型。然而，该综合征的所有特征并未都得到体现。干细胞被认为是分子和再生医学的未来。几种类型的干细胞可以提供一种有效的方法，为一些无法治疗的人类疾病提供潜在治疗。干细胞也是开发新的基于细胞的药物和/或研究分子疾病途径模型的有效系统。在干细胞类型中，患者来源的诱导多能干细胞（iPS细胞）在细胞和组织替代、工程和研究方面具有一些优势：自我更新能力、多能性以及获取供体组织的便利性。这些细胞可以重新编程为完全不同的细胞类型。它们是通过异位表达四种转录因子（Oct3/4、Sox2、c-Myc和Klf4；或者Oct3/4、Sox2、Nanog和Lin28）从成体细胞重新编程而来。通过对DS患者的细胞进行重新编程，可以获得具有相同遗传背景的新组织，为研究这种遗传疾病和设计定制的患者特异性干细胞疗法提供了有价值的工具。
