Toward better assessments of developmental toxicity using stem cell-based in vitro embryogenesis models.
Toward better assessments of developmental toxicity using stem cell-based in vitro embryogenesis models.
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DOI：
10.1002/bdr2.1984
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发表时间：
2022-10-01
影响因子：
2.1
通讯作者：
Marikawa, Yusuke
中科院分区：
文献类型：
--
作者：
Marikawa, Yusuke
在过去的几十年中，多能干细胞已被探索作为非动物替代品来评估化学品的发育毒性。迄今为止，已有多种基于干细胞的检测方法被报道，据称是有效的。尽管如此，这些检测都还没有成为发育毒性评估的金标准。为什么？本文讨论了几个问题，希望能够促进干细胞检测的完善并使其被接受为预测发育毒理学的基石。每一种干细胞检测都是建立在胚胎发生的有限表征之上的，因此需要多种检测来检测各种化学物质的不同作用。为了验证和比较各个测定的优点和缺点，应建立标准化的参考化学品清单。参考列表应包括由毒代动力学数据定义的暴露，即导致胚胎死亡或畸形的母体血浆浓度，以及对控制胚胎发生的分子机制的影响。尽管不能完全取代人体或动物测试，但精心挑选的干细胞检测应作为实用且合乎道德的替代方案，以主动识别干扰胚胎发生的化学暴露。为了实现这一目标，研究界和监管界之间需要前所未有的协调和信念。
In the past few decades, pluripotent stem cells have been explored as nonanimal alternatives to assess the developmental toxicity of chemicals. To date, numerous versions of stem cell‐based assays have been reported that are allegedly effective. Nonetheless, none of the assays has become the gold standard in developmental toxicity assessment. Why? This article discusses several issues in the hope of facilitating the refinement of stem cell assays and their acceptance as the cornerstone in predictive developmental toxicology. Each stem cell assay is built on a limited representation of embryogenesis, so that multiple assays are needed to detect the diverse effects of various chemicals. To validate and compare the strengths and weaknesses of individual assays, standardized lists of reference chemicals should be established. Reference lists should consist of exposures defined by toxicokinetic data, namely maternal plasma concentrations that cause embryonic death or malformations, and also by the effects on the molecular machineries that control embryogenesis. Although not entirely replacing human or animal tests, carefully selected stem cell assays should serve as practical and ethical alternatives to proactively identify chemical exposures that disturb embryogenesis. To achieve this goal, unprecedented levels of coordination and conviction are required among research and regulatory communities.
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DOI：
10.1093/toxsci/kfab097
发表时间：
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期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
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DOI：
10.1007/978-1-61779-867-2_3
发表时间：
2012
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
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作者：
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