Adult Stem Cell Research Center, Laboratory for Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Sillim-Dong, Seoul 151-742, Korea.
Toxicol Sci. 2011 Mar;120 Suppl 1:S269-89. doi: 10.1093/toxsci/kfq370. Epub 2010 Dec 16.
This "Commentary" has examined the use of human stem cells for detection of toxicities of physical, chemical, and biological toxins/toxicants in response to the challenge posed by the NRC Report, "Toxicity Testing in the 21st Century: A vision and Strategy." Before widespread application of the use of human embryonic, pluripotent, "iPS," or adult stem cells be considered, the basic characterization of stem cell biology should be undertaken. Because no in vitro system can mimic all factors that influence cells in vivo (individual genetic, gender, developmental, immunological and diurnal states; niche conditions; complex intercellular interactions between stem, progenitor, terminal differentiated cells, and the signaling from extracellular matrices, oxygen tensions, etc.), attempts should be made to use both embryonic and adult stem cells, grown in three dimension under "niche-like" conditions. Because many toxins and toxicants work by "epigenetic" mechanisms and that epigenetic mechanisms play important roles in regulating gene expression and in the pathogenesis of many human diseases, epigenetic toxicity must be incorporated in toxicity testing. Because modulation of gap junctional intercellular communication by epigenetic agents plays a major role in homeostatic regulation of both stem and progenitor cells in normal tissues, the modulation of this biological process by both endogenous and endogenous chemicals should be incorporated as an end point to monitor for potential toxicities or chemo-preventive attributes. In addition, modulation of quantity, as well as the quality, of stem cells should be considered as potential source of a chemical's toxic potential in affecting any stem cell-based pathology, such as cancer.
本“评论”考察了人类干细胞在检测物理、化学和生物毒素/毒物毒性方面的应用，以应对 NRC 报告“21 世纪的毒性测试：愿景与策略”所提出的挑战。在广泛应用人类胚胎、多能性、“iPS”或成体干细胞之前，应该对干细胞生物学的基本特征进行研究。由于没有体外系统可以模拟所有影响体内细胞的因素（个体遗传、性别、发育、免疫和昼夜状态；生态位条件；干细胞、祖细胞、终末分化细胞之间的复杂细胞间相互作用，以及来自细胞外基质、氧张力等的信号），应该尝试使用胚胎和成体干细胞，在类似于生态位的条件下进行三维培养。由于许多毒素和毒物通过“表观遗传”机制起作用，并且表观遗传机制在调节基因表达和许多人类疾病的发病机制中起着重要作用，因此必须将表观遗传毒性纳入毒性测试中。由于表观遗传剂对细胞间隙通讯的调节在正常组织中干细胞和祖细胞的稳态调节中起着重要作用，因此应该将这种生物过程的调节纳入监测潜在毒性或化学预防属性的终点。此外，应该考虑干细胞数量和质量的调节，作为化学物质毒性潜力的潜在来源，以影响任何基于干细胞的病理学，如癌症。
