Human-Derived Corneal Epithelial Cells Expressing Cell Cycle Regulators as a New Resource for in vitro Ocular Toxicity Testing

Human-Derived Corneal Epithelial Cells Expressing Cell Cycle Regulators as a New Resource for in vitro Ocular Toxicity Testing
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DOI:
10.3389/fgene.2019.00587
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发表时间:
2019-07-16
影响因子:
3.7
通讯作者:
Kiyono, Tohru
Kiyono, Tohru
中科院分区:
生物学3区
文献类型:
--
作者:
Fukuda, Tomokazu;Gouko, Ryo;Kiyono, Tohru

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自20世纪60年代以来,Draze测试一直在兔子身上使用,以评估化妆品或美发产品等产品中商业化学品造成的刺激性。然而,自2003年以来,包括化妆品德雷兹测试在内的此类测试在欧洲国家被禁止,因为它们被认为对动物福利有问题。因此,用体外方法替代体内方法已成为一个重要的目标。在这项研究中,我们建立了一种共表达突变的细胞周期蛋白依赖性激酶4(CDK4)、细胞周期蛋白D1和端粒酶逆转录酶(TERT)的角膜上皮细胞系。建立的细胞系保持了原有的形态,并有较高的增殖率。此外,在使用乙醇酸和苯扎氯铵的刺激试验中,细胞的存活率显示出显著的剂量依赖性下降。这些细胞现在可以与毒理学科学家共享,应该有助于提高体外化学测试的重复性。
The Draize test has been used on rabbits since the 1960s to evaluate the irritation caused by commercial chemicals in products such as cosmetics or hairdressing products. However, since 2003, such tests, including the Draize test for cosmetics, have been prohibited in European countries because they are considered problematic to animal welfare. For this reason, replacement of in vivo methods with the alternative in vitro methods has become an important goal. In this study, we established a corneal epithelial cell line co-expressing a mutant cyclin-dependent kinase 4 (CDK4), Cyclin D1, and telomerase reverse transcriptase (TERT). The established cell line maintained its original morphology and had an enhanced proliferation rate. Furthermore, the cells showed a significant, dose-dependent decrease in viability in an irritation test using glycolic acid and Benzalkonium chloride. These cells can now be shared with toxicology scientists and should contribute to increasing the reproducibility of chemical testing in vitro.