A novel human pluripotent stem cell-based assay to predict developmental toxicity.

Content Provider	Europe PMC
Author	Lauschke, Karin Rosenmai, Anna Kjerstine Meiser, Ina Neubauer, Julia Christiane Schmidt, Katharina Rasmussen, Mikkel Aabech Holst, Bjørn Taxvig, Camilla Emnéus, Jenny Katarina Vinggaard, Anne Marie
Abstract	There is a great need for novel in vitro methods to predict human developmental toxicity to comply with the 3R principles and to improve human safety. Human-induced pluripotent stem cells (hiPSC) are ideal for the development of such methods, because they are easy to retrieve by conversion of adult somatic cells and can differentiate into most cell types of the body. Advanced three-dimensional (3D) cultures of these cells, so-called embryoid bodies (EBs), moreover mimic the early developing embryo. We took advantage of this to develop a novel human toxicity assay to predict chemically induced developmental toxicity, which we termed the PluriBeat assay. We employed three different hiPSC lines from male and female donors and a robust microtiter plate-based method to produce EBs. We differentiated the cells into cardiomyocytes and introduced a scoring system for a quantitative readout of the assay—cardiomyocyte contractions in the EBs observed on day 7. Finally, we tested the three compounds thalidomide (2.3–36 µM), valproic acid (25–300 µM), and epoxiconazole (1.3–20 µM) on beating and size of the EBs. We were able to detect the human-specific teratogenicity of thalidomide and found the rodent toxicant epoxiconazole as more potent than thalidomide in our assay. We conclude that the PluriBeat assay is a novel method for predicting chemicals’ adverse effects on embryonic development.Electronic supplementary materialThe online version of this article (10.1007/s00204-020-02856-6) contains supplementary material, which is available to authorized users.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7603451&blobtype=pdf
ISSN	03405761
Journal	Archives of Toxicology [Arch Toxicol]
Volume Number	94
DOI	10.1007/s00204-020-02856-6
PubMed Central reference number	PMC7603451
Issue Number	11
PubMed reference number	32700165
e-ISSN	14320738
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2020-07-22
Publisher Place	Berlin/Heidelberg
Access Restriction	Open
Rights License	Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2020
Subject Keyword	Human-induced pluripotent stem cells Embryonic stem cell test Developmental toxicity Thalidomide Epoxiconazole Valproic acid
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Medicine Toxicology