Aberdam Edith, Barak Efrat, Rouleau Matthieu, de LaForest Stephanie, Berrih-Aknin Sonia, Suter David M, Krause Karl-Heinz, Amit Michal, Itskovitz-Eldor Joseph, Aberdam Daniel
Institut National de la Santé et de la Recherche Médicale U898, Nice, France.
Stem Cells. 2008 Feb;26(2):440-4. doi: 10.1634/stemcells.2007-0588. Epub 2007 Nov 21.
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.
胚胎干细胞(ES细胞)是一种独特的细胞模型,可在体外概括胚胎发育的早期步骤,也是治疗多种疾病的无限细胞来源,同时还是药物发现和毒理学筛选的靶点。尽管此前的研究已报道了小鼠和人胚胎干细胞(huES细胞)的表皮分化,但所得细胞培养物的异质性不利于对用于细胞治疗的分化细胞进行评估。我们在此报告了从人ES细胞中可重复分离出一种同质的外胚层细胞群体IT1。与原代细胞一样,IT1细胞在超过15次传代后仍保持同质,可扩增多达60次群体倍增,然后因衰老而死亡。因此,IT1细胞显示出正常的核型和体细胞周期动力学,且在裸鼠中不产生畸胎瘤。由p63表达驱动的表达K14的上皮细胞的产生强化了IT1细胞的外胚层性质。由于IT1可从不同的huES细胞系中分离得到,它可能为毒理学细胞模型的开发、新药筛选策略及细胞治疗移植提供现成的外胚层祖细胞来源。