Assessment of Developmental Toxicants using Human Embryonic Stem Cells

Abstract

Embryonic stem (ES) cells have potential for use in evaluation of developmental toxicity because they are generated in large numbers and differentiate into three germ layers following formation of embryoid bodies (EBs). In earlier study, embryonic stem cell test (EST) was established for assessment of the embryotoxic potential of compounds. Using EBs indicating the onset of differentiation of mouse ES cells, many toxicologists have refined the developmental toxicity of a variety of compounds. However, due to some limitation of the EST method resulting from species-specific differences between humans and mouse, it is an incomplete approach. In this regard, we examined the effects of several developmental toxic chemicals on formation of EBs using human ES cells. Although human ES cells are fastidious in culture and differentiation, we concluded that the relevancy of our experimental method is more accurate than that of EST using mouse ES cells. These types of studies could extend our understanding of how human ES cells could be used for monitoring developmental toxicity and its relevance in relation to its differentiation progress. In addition, this concept will be used as a model system for screening for developmental toxicity of various chemicals. This article might update new information about the usage of embryonic stem cells in the context of their possible ability in the toxicological fields.

Re-registration Challenges of Glyphosate in the European Union

“…Moreover, Roundup Full II R exerted acute toxicity (LC 50 = 0.009 mg/ml upon 96 h of exposure) and genotoxic effects in blood, gill, and liver cells of the pacu fish (Piaractus mesopotamicus) determined in comet micronucleus and nuclear abnormalities assays (Leveroni et al, 2017). Roundup Transorb R was found mutagenic and genotoxic on gill erythrocyte cells of the guppy Poecilia reticulata (De Souza Filho et al, 2013), and a glyphosate-based herbicide at dilutions corresponding to glyphosate concentrations above 1.7 ng/ml caused significant decreases in the numbers of differentiated neuronal clusters and myotubes on primary embryonic stem cells from Drosophila melanogaster, being indicative of potential teratogenic effects (Argueta and Torres, 2017).…”

An engineered mouse embryonic stem cell model with survivin as a molecular marker and EGFP as the reporter for high throughput screening of embryotoxic chemicals in vitro

“…The gene expression profiles of mouse and human ES cells have been proven to be distinct in, for example, several differentiation markers (Liu, Yin, & Faiola, 2017;Tandon & Jyoti, 2012;Wobus & Loser, 2011), which may lead to completely different responses to the test chemicals in molecular approaches (Yamane et al, 2016). Several recent studies have thus investigated the potential application of human embryonic stem cells (hESCs), associated with a variety of molecular endpoints, to predict the developmental toxicity in vitro (Ehashi, Suzuki, Ando, Sumida, & Saito, 2014;Hong & Jeung, 2013;Jung et al, 2014;Sandstrom et al, 2017). However, in addition to ethical issues, using hESCs for drug screening not only requires complex culturing conditions but also is costly and difficult to implement in the HT manner (Fang, Zhi, Yu, Lynch, & Jia, 2018;Rezvanfar, Hodjat, & Abdollahi, 2016).…”

Cell-based in vitro models in environmental toxicology: a review

“…More consistent results were obtained using embryonic stem cells to evaluate the effects of toxins on either the progress of differentiation or to compare their sensitivity (viability) to cells from matured tissue [141][142][143][144]. These cells can be cultured in form of aggregates or micromass cultures where cell functions like adhesion, movement, communication and division are kept intact at a basal level [145].…”