Department of Cell Biology and Neuroscience, University of California, Riverside, CA 92521, USA.
Curr Top Med Chem. 2011;11(13):1638-52. doi: 10.2174/156802611796117621.
Given the vast number of chemicals that are released into the environment each year, it is imperative that we develop new predictive models to identify toxicants before unavoidable exposure harms the health of humans and other organisms. In vitro models are especially attractive in predictive toxicology as they can greatly reduce assay costs and animal usage while identifying those chemicals that may require further in vivo evaluation. With the derivation of both mouse and human embryonic stem cells, new opportunities have developed that could revolutionize the field of predictive toxicology. Stem cells themselves can be used to model earliest stages of development, or they can be differentiated to study later aspects of development and thereby model post-implantation. Because embryos and fetuses are usually more sensitive to environmental toxicants than adults, stem cells provide an unique tool for studying the prenatal phase in our life cycle. The embryonic stem cell test (EST), which has been validated for use with mouse ESC (mESC), is an accurate predictor of embryotoxic compounds, particularly those that are highly embryotoxic. Human embryonic stem cells (hESCs), although not yet incorporated into a validated test, are a particularly attractive platform for toxicological testing as they can give us direct information on humans and avoid concerns about species variation in response. This review discusses toxicological studies and strategies that have been used with embryonic stem cells during the past five years and possible directions that could lead to improvements in the development of predictive assays in the future.
鉴于每年有大量的化学物质释放到环境中，我们必须开发新的预测模型，以便在不可避免的暴露对人类和其他生物的健康造成危害之前识别出有毒物质。在预测毒理学中，体外模型特别有吸引力，因为它们可以大大降低检测成本和动物使用量，同时识别出那些可能需要进一步体内评估的化学物质。随着小鼠和人类胚胎干细胞的衍生，新的机会已经出现，这可能会彻底改变预测毒理学领域。干细胞本身可用于模拟发育的最早阶段，也可分化为研究发育的后期阶段，从而模拟植入后阶段。由于胚胎和胎儿通常比成人对环境有毒物质更敏感，因此干细胞为研究我们生命周期中的产前阶段提供了独特的工具。已经验证可用于小鼠 ESC（mESC）的胚胎干细胞测试（EST）是胚胎毒性化合物的准确预测因子，特别是那些高度胚胎毒性的化合物。人胚胎干细胞（hESC）虽然尚未纳入验证测试，但作为毒理学测试的一个特别有吸引力的平台，因为它们可以为我们提供有关人类的直接信息，并避免对物种差异反应的担忧。这篇综述讨论了过去五年中使用胚胎干细胞进行的毒理学研究和策略，以及可能导致未来预测性检测方法发展改进的可能方向。
