A pure population of ectodermal cells derived from human embryonic stem cells

A pure population of ectodermal cells derived from human embryonic stem cells
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DOI:
10.1634/stemcells.2007-0588
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发表时间:
2008-02-01
期刊:
影响因子:
5.2
通讯作者:
Aberdam, Daniel
Aberdam, Daniel
中科院分区:
医学2区
文献类型:
--
作者:
Aberdam, Edith;Barak, Efrat;Aberdam, Daniel

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胚胎干细胞是一种独特的细胞模型,可以概括体外胚胎发育的早期步骤,是许多疾病治疗的无限细胞来源,也是药物发现和毒理学筛选的靶标。尽管先前的研究已经报道了小鼠和人类胚胎干细胞(huES)的表皮分化,但由此产生的细胞培养的异质性损害了对分化细胞进行细胞治疗的评估。我们在此报告了从人类胚胎干细胞中可重复性地分离出同质外胚层细胞群IT1。像原代细胞一样,IT1细胞在15代传代中保持同质性,扩增到60倍,然后因衰老而死亡。因此,IT1细胞在裸鼠体内表现出正常的核型和体细胞周期动力学,不产生畸胎瘤。由p63表达驱动的表达k14的上皮细胞的产生增强了IT1细胞的外胚层性质。由于IT1可以从不同色系的es细胞系中分离出来,它可能为毒理学细胞模型、新药筛选策略和细胞治疗移植的发展提供一个现成的外胚层祖细胞来源。
Embryonic stem (ES) cells represent a unique cellular model to recapitulate in vitro early steps of embryonic development and an unlimited cellular source in therapy for many diseases, as well as targets for drug discovery and toxicology screens. Although previous studies have reported epidermal differentiation of mouse and human embryonic stem (huES) cells, the heterogeneity of the resulting cell culture impairs the evaluation of differentiated cells for cell therapy. We report here the reproducible isolation of a homogenous ectodermal cell population, IT1 from human ES cells. Like primary cells, IT1 cells remain homogenous over 15 passages, expand up to 60 population doublings, and then die through senescence. Accordingly, IT1 cells display a normal karyotype and a somatic cell cycle kinetics and do not produce teratoma in nude mice. The production of K14-expressing epithelial cells driven by p63 expression strengthens the ectodermal nature of IT1 cells. Since IT1 can be isolated from different huES cell lines, it may provide a ready source of ectodermal progenitors for the development of a toxicology cell model, new-drug-screening strategies, and cell therapy transplantation.