Stem Cells in Toxicology: Fundamental Biology and Practical Considerations
Stem Cells in Toxicology: Fundamental Biology and Practical Considerations
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DOI：
10.1093/toxsci/kfq370
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发表时间：
2011-03-01
影响因子：
3.8
通讯作者：
Trosko, James E.
中科院分区：
文献类型：
--
作者：
Kang, Kyung-Sun;Trosko, James E.
这篇“评论”研究了利用人类干细胞检测物理、化学和生物毒素/毒物的毒性，以应对NRC报告“21世纪的毒性测试：愿景和战略”提出的挑战。在考虑广泛应用人类胚胎干细胞、多能干细胞、“iPS”干细胞或成体干细胞之前，应先进行干细胞生物学的基本鉴定。因为没有体外系统可以模拟体内影响细胞的所有因素（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的信号传导、氧张力等），应当尝试使用在“类小生境”条件下三维生长的胚胎干细胞和成体干细胞。由于许多毒素和毒物通过“表观遗传”机制发挥作用，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发挥重要作用，因此必须将表观遗传毒性纳入毒性测试。由于调节间隙连接细胞间通讯的表观遗传剂在正常组织中的干细胞和祖细胞的稳态调节中起着重要作用，内源性和内源性化学物质对这一生物过程的调节应作为监测潜在毒性或化学预防属性的终点。此外，干细胞数量和质量的调节应被视为化学品在影响任何基于干细胞的病理学（如癌症）方面的潜在毒性来源。
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.