The Rise of Stem Cell Toxicology

摘要

The field of environmental toxicology has been challenged in the last few decades by the exponential discovery of novel persistent pollutants and the relative lack of knowledge of their hazardousness to human health. At the same time, there has been increasing awareness of the urgency and necessity of innovative, validated, and comprehensive assays to collect toxicity data more relevant to humans. Since the onset of toxicology science, we have heavily relied on animal tests. Although these in vivo experiments have been refined in recent years, they are still expensive, labor intensive, time-consuming, and accompanied by ethical issues. More importantly, Russell and Burch's "high fidelity fallacy" theory postulates that toxicity assays with animals are not always applicable to human health due to interspecies variations, even when primates are used. A prototypical example is the case of the drug thalidomide, proven to be highly teratogenic in humans even though it had passed all animal tests. This led to the introduction of in vitro tests as alternatives to in vivo animal experiments (reviewed in ref 2). In particular, the culture of human cells for toxicity tests, more directly relevant to human health, has been the primary solution to the obvious fact that humans cannot be used for in vivo studies. However, the direct derivation of some types of primary human cells, can be extremely invasive or simply impossible, and even if successful, the ability of primary cells to be cultured and expanded in vitro is limited. Conversely, immortalized or cancer cell lines can be readily grown and amplified in dishes; nevertheless, they may no longer be representative of the cells of origin because of accumulating mutations or altered cell functions, for example. Collectively, these issues can greatly affect the generation and interpretation of toxicity data. However, as described below, new stem cell technologies for the in vitro analyses of pollutants' potential hazardousness, allow scientists to move past these problems.