Kugler Josephine, Huhse Bettina, Tralau Tewes, Luch Andreas
a Department of Chemical & Product Safety , German Federal Institute for Risk Assessment (BfR) , Berlin , Germany.
Expert Opin Drug Metab Toxicol. 2017 Aug;13(8):833-841. doi: 10.1080/17425255.2017.1351548. Epub 2017 Jul 12.
The advent of stem cell technology has seen the establishment of embryonic stem cells (ESCs) as molecular model systems and screening tools. Although ESCs are nowadays widely used in research, regulatory implementation for developmental toxicity testing is pending. Areas Covered: This review evaluates the performance of current ESC, including human (h)ESC testing systems, trying to elucidate their potential for developmental toxicity testing. It shall discuss defining parameters and mechanisms, their relevance and contemplate what can realistically be expected. Crucially this includes the question of how to ascertain the quality of currently employed cell lines and tests based thereon. Finally, the use of hESCs will raise ethical concerns which should be addressed early on. Expert Opinion: While the suitability of (h)ESCs as tools for research and development goes undisputed, any routine use for developmental toxicity testing currently still seems premature. The reasons for this comprise inherent biological deficiencies as well as cell line quality and system validation. Overcoming these issues will require collaboration of scientists, test developers and regulators. Also, validation needs to be made worthwhile for academia. Finally we have to continuously rethink existing strategies, making room for improved testing and innovative approaches.
干细胞技术的出现见证了胚胎干细胞（ESC）作为分子模型系统和筛选工具的确立。尽管如今ESC在研究中被广泛使用，但用于发育毒性测试的监管实施仍在等待中。涵盖领域：本综述评估了当前ESC的性能，包括人类（h）ESC测试系统，试图阐明它们在发育毒性测试中的潜力。它将讨论定义参数和机制、它们的相关性，并思考实际可以期待什么。至关重要的是，这包括如何确定当前使用的细胞系的质量以及基于此的测试。最后，hESC的使用将引发伦理问题，应尽早解决。专家意见：虽然（h）ESC作为研发工具的适用性无可争议，但目前将其用于发育毒性测试的任何常规用途似乎仍为时过早。其原因包括固有的生物学缺陷以及细胞系质量和系统验证。克服这些问题将需要科学家、测试开发者和监管机构的合作。此外，验证需要对学术界有价值。最后，我们必须不断重新思考现有策略，为改进测试和创新方法留出空间。
