Pre-validation study of alternative developmental toxicity test using mouse embryonic stem cell-derived embryoid bodies

Pluripotent stem cell assays: Modalities and applications for predictive developmental toxicity

“…One exception is an observed effective concentration at 4.4 µg/ml ( West et al, 2010 ). In other cell types the effective concentrations were equal to the effective concentration in PSC, with one exception ( Lee et al, 2019 ) in which fibroblasts were less sensitive. Without the consideration of plasma concentrations in humans, the in vitro results would be as equivocal as the in vivo results are interpreted.…”

“…The results of the intra- and inter-laboratory tests had an accuracy above 80% when substances were classified using the predictive model. In this report, EBT can accurately classify various embryotoxicants in a short time with less effort and greater validation to reflect ‘growth retardation and embryo mortality’ ( Lee et al, 2019 ). Therefore, the EBT may be most sensitive to chemicals that exhibit cytotoxicity toward the cells (which may lead to a negative developmental outcome) raising question as to the sensitivity of EBT to detect chemicals that truly elicit a developmental inhibition in the absence of generalized alterations on EB mass.…”

“…EB growth can be monitored using high-content imaging (HCI) devices. Recently, a pre-validation study of the EBT was conducted in Korea ( Lee et al, 2019 ). This pre-validation study evaluated the predictive accuracy of the EBT using 26 coded test substances by two steps: intra-laboratory and inter-laboratory reproducibility tests.…”

“… Legend to table 1: ESC embryonic stem cells; IPSC induced pluripotent stem cells; CM cardiomyocytes; EB embryoid bodies. References to Table 1 : ( Laschinski et al, 1991 , Newall and Beedles, 1996 , Genschow et al, 2004 , Paquette et al, 2008 , West et al, 2010 , Kleinstreuer et al, 2011 , Suzuki et al, 2011 , Palmer et al, 2013 , Panzica-Kelly et al, 2013 , Kameoka et al, 2014 , Cheng et al, 2016 , Nagahori et al, 2016 , Lee et al, 2019 , Kawamura et al, 2019 , Zang et al, 2019 , Aikawa, 2020 , Marikawa et al, 2020 , Zurlinden et al, 2020 , Lee et al, 2020 , van Oostrom et al, 2020 ). …”

“…7 ). Murine ESCs in the included publications used additional endpoints in combination with the cell viability: the size of embryoid bodies ( Lee et al, 2020 ) and mRNA expression analyses ( Panzica-Kelly et al, 2013 ). However, both murine ESC studies were not able to predict the teratogenic potential correctly, testing up to the maximum soluble concentration.…”