Stem Cell Toxicology Group, National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Toxicol Sci. 2018 Sep 1;165(1):31-39. doi: 10.1093/toxsci/kfy174.
Millions of children are born each year with a birth defect. Many of these defects are caused by environmental factors, although the underlying etiology is often unknown. In vivo mammalian models are frequently used to determine if a chemical poses a risk to the developing fetus. However, there are over 80 000 chemicals registered for use in the United States, many of which have undergone little safety testing, necessitating the need for higher-throughput methods to assess developmental toxicity. Pluripotent stem cells (PSCs) are an ideal in vitro model to investigate developmental toxicity as they possess the capacity to differentiate into nearly any cell type in the human body. Indeed, a burst of research has occurred in the field of stem cell toxicology over the past decade, which has resulted in numerous methodological advances that utilize both mouse and human PSCs, as well as cutting-edge technology in the fields of metabolomics, transcriptomics, transgenics, and high-throughput imaging. Here, we review the wide array of approaches used to detect developmental toxicants, suggest areas for further research, and highlight critical aspects of stem cell biology that should be considered when utilizing PSCs in developmental toxicity testing.
每年都有数百万儿童出生时带有出生缺陷。这些缺陷中有许多是由环境因素引起的，尽管其根本病因通常未知。体内哺乳动物模型常用于确定一种化学物质是否对发育中的胎儿构成风险。然而，在美国有超过 80000 种化学品注册用于使用，其中许多化学品几乎没有经过安全性测试，这就需要采用高通量方法来评估发育毒性。多能干细胞（PSCs）是一种理想的体外模型，可用于研究发育毒性，因为它们具有分化为人体内几乎任何细胞类型的能力。事实上，过去十年间，干细胞毒理学领域发生了大量研究，从而导致了许多利用小鼠和人 PSCs 的方法学进展，以及代谢组学、转录组学、转基因和高通量成像等领域的尖端技术。在这里，我们回顾了用于检测发育毒物的广泛方法，提出了进一步研究的领域，并强调了在利用 PSCs 进行发育毒性测试时应考虑的干细胞生物学的关键方面。
