Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
Biomedical Center for Animal Resource and Development, Seoul National University College of Medicine, Seoul, Republic of Korea.
Regul Toxicol Pharmacol. 2019 Jul;105:15-29. doi: 10.1016/j.yrtph.2019.03.016. Epub 2019 Mar 28.
Despite a major role of experimental animals in development of biomedical research, there has been historical controversy surrounding animal research. Along with a strategy of 3Rs, various in vitro methods have been suggested to replace potentially painful animal experiments. In this review, we summarize the use of stem cells as an alternative of animal experimentation in predictive toxicology. There have been continuing researches on stem cells and stem cell-derived tissue-specific cells to develop alternative methods/biomarkers for animal toxicity testing including developmental toxicity, genotoxicity, and tissue-specific toxicity. Along with unique abilities of stem cells including self-renewal, infinite proliferation, and differentiation into multiple lineages, human stem cell-based in vitro systems have been proven valuable to increase predictive power of toxicology through providing with better scientific information related to toxic risks in humans without inter-species variability. In particular, stem cells including induced pluripotent stem cell-based system for personalized toxicological assessment could be a better option as an in vitro model system in comparison with immortalized cells with abnormal phenotype or primary cells with small quantity and batch-to-batch variation. This review will be useful for understanding the current status and future direction in using stem cells as an alternative non-animal method for predictive toxicology.
尽管实验动物在生物医学研究的发展中起着重要作用,但动物研究一直存在历史争议。除了 3R 策略外,还提出了各种体外方法来替代潜在痛苦的动物实验。在这篇综述中,我们总结了将干细胞用作动物实验替代物在预测毒理学中的应用。人们一直在研究干细胞和干细胞衍生的组织特异性细胞,以开发替代方法/生物标志物,用于动物毒性测试,包括发育毒性、遗传毒性和组织特异性毒性。干细胞具有自我更新、无限增殖和分化为多个谱系的独特能力,基于人干细胞的体外系统已被证明通过提供与人类毒性风险相关的更好的科学信息而增加毒理学的预测能力,而没有种间变异性。特别是,基于诱导多能干细胞的个性化毒理学评估的干细胞系统可能是一种更好的选择,因为与具有异常表型的永生化细胞或数量小、批次间变化大的原代细胞相比,它是一种更好的体外模型系统。这篇综述将有助于了解使用干细胞作为预测毒理学替代非动物方法的现状和未来方向。