Rohwedel J, Guan K, Hegert C, Wobus A M
Dept of Medical Molecular Biology, University of Lübeck, D-23538, Lübeck, Germany.
Toxicol In Vitro. 2001 Dec;15(6):741-53. doi: 10.1016/s0887-2333(01)00074-1.
Primary cultures or established cell lines of vertebrates are commonly used to analyse the mutagenic, embryotoxic or teratogenic potential of environmental factors, drugs and xenobiotics in vitro. However, these cellular systems do not include developmental processes from early embryonic stages up to terminally differentiated cell types. An alternative approach has been offered by permanent lines of pluripotent stem cells of embryonic origin, such as embryonic carcinoma (EC), embryonic stem (ES) and embryonic germ (EG) cells. The undifferentiated stem cell lines are characterized by nearly unlimited self-renewal capacity and have been shown to differentiate in vitro into cells of all three primary germ layers. Pluripotent embryonic stem cell lines recapitulate cellular developmental processes and gene expression patterns of early embryogenesis during in vitro differentiation, data which are summarized in this review. In addition, recent studies are presented which investigated mutagenic, cytotoxic and embryotoxic effects of chemical substances using in vitro systems of pluripotent embryonic stem cells. Furthermore, an outlook is given on future molecular technologies using embryonic stem cells in developmental toxicology and embryotoxicology.
脊椎动物的原代培养物或已建立的细胞系通常用于在体外分析环境因素、药物和异生物素的致突变性、胚胎毒性或致畸性。然而，这些细胞系统并不包括从早期胚胎阶段到终末分化细胞类型的发育过程。胚胎来源的多能干细胞的永久系，如胚胎癌（EC）、胚胎干细胞（ES）和胚胎生殖（EG）细胞，提供了另一种方法。未分化的干细胞系的特点是具有几乎无限的自我更新能力，并且已被证明在体外可分化为所有三个原始胚层的细胞。多能胚胎干细胞系在体外分化过程中概括了早期胚胎发生的细胞发育过程和基因表达模式，本文综述了这些数据。此外，还介绍了最近利用多能胚胎干细胞体外系统研究化学物质的致突变、细胞毒性和胚胎毒性作用的研究。此外，还展望了未来在发育毒理学和胚胎毒理学中使用胚胎干细胞的分子技术。
