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从人尿液诱导多能干细胞中衍生和鉴定运动神经元

Derivation and Identification of Motor Neurons from Human Urine-Derived Induced Pluripotent Stem Cells.

作者信息

Yi Huan, Xie Bingbing, Liu Ben, Wang Xuan, Xu Li, Liu Jia, Li Min, Zhong Xiufeng, Peng Fuhua

机构信息

Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510600, China.

出版信息

Stem Cells Int. 2018 Jan 24;2018:3628578. doi: 10.1155/2018/3628578. eCollection 2018.

Abstract

Induced pluripotent stem cells (iPSCs) have provided new opportunities for motor neuron disease (MND) modeling, drug screening, and cellular therapeutic development. Among the various types of iPSCs, urine-derived iPSCs have become a promising source of stem cells because they can be safely and noninvasively isolated and easily reprogrammed. Here, for the first time, we differentiated urine-derived iPSCs (urine-iPSCs) into motor neurons (MNs) and compared the capacity of urine-iPSCs and cord-blood-derived iPSCs (B-iPSCs) to differentiate into MNs. With the use of small molecules, mature MNs were generated from urine-iPSCs as early as 26 days in culture. Furthermore, in coculture with muscle cells, MNs projected long axons and formed neuromuscular junctions (NMJs). Immunofluorescence and PCR confirmed the expression levels of both MN and NMJ markers. The comparison of the ratios of positive labeling for MN markers between urine-iPSCs and B-iPSCs demonstrated that the differentiation potentials of these cells were not significantly different. The abovementioned results indicate that urine-iPSCs are a new, promising source of stem cells for MND modeling and further cellular therapeutic development.

摘要

诱导多能干细胞(iPSCs)为运动神经元疾病(MND)建模、药物筛选和细胞治疗开发提供了新的机遇。在各种类型的iPSCs中,尿液来源的iPSCs已成为一种有前景的干细胞来源,因为它们可以安全、无创地分离且易于重编程。在此,我们首次将尿液来源的iPSCs(尿液-iPSCs)分化为运动神经元(MNs),并比较了尿液-iPSCs和脐带血来源的iPSCs(B-iPSCs)分化为MNs的能力。通过使用小分子,早在培养26天时就从尿液-iPSCs中生成了成熟的MNs。此外,在与肌肉细胞共培养时,MNs伸出长轴突并形成神经肌肉接头(NMJs)。免疫荧光和PCR证实了MN和NMJ标志物的表达水平。尿液-iPSCs和B-iPSCs之间MN标志物阳性标记率的比较表明,这些细胞的分化潜能没有显著差异。上述结果表明,尿液-iPSCs是用于MND建模和进一步细胞治疗开发的一种新的、有前景的干细胞来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64af/5829358/0156c22f447d/SCI2018-3628578.001.jpg

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