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Related Concept Videos

Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore called induced pluripotent stem...

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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
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A novel human pluripotent stem cell-based assay to predict developmental toxicity.

Karin Lauschke1,2, Anna Kjerstine Rosenmai1, Ina Meiser3

  • 1National Food Institute, Technical University of Denmark, Kemitorvet, 2800, Kongens Lyngby, Denmark.

Archives of Toxicology
|July 24, 2020
PubMed
Summary

A new PluriBeat assay using human stem cells predicts developmental toxicity. This in vitro method detects chemical effects on early embryonic development, offering a safer alternative for toxicity testing.

Keywords:
Developmental toxicityEmbryonic stem cell testEpoxiconazoleHuman-induced pluripotent stem cellsThalidomideValproic acid

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Area of Science:

  • Toxicology
  • Stem Cell Biology
  • Developmental Biology

Background:

  • There is a critical need for advanced in vitro methods to predict human developmental toxicity, aligning with the 3R principles and enhancing human safety.
  • Human-induced pluripotent stem cells (hiPSC) are valuable for developing such assays due to their differentiation potential and ease of acquisition.
  • Three-dimensional (3D) cultures, specifically embryoid bodies (EBs), derived from hiPSCs effectively mimic early embryonic development.

Purpose of the Study:

  • To develop and validate a novel human in vitro toxicity assay, termed the PluriBeat assay, for predicting chemical-induced developmental toxicity.
  • To utilize hiPSC-derived embryoid bodies (EBs) to model early human embryonic development and assess chemical teratogenicity.
  • To establish a quantitative readout for the assay based on cardiomyocyte contraction within EBs.

Main Methods:

  • Three distinct hiPSC lines from male and female donors were used to generate EBs via a microtiter plate-based method.
  • EBs were differentiated into cardiomyocytes, and their contractions were quantitatively assessed on day 7 as a primary assay readout.
  • The assay was validated by testing known developmental toxicants: thalidomide, valproic acid, and epoxiconazole at specified concentrations.

Main Results:

  • The PluriBeat assay successfully detected the human-specific teratogenicity of thalidomide.
  • Epoxiconazole, a known rodent toxicant, demonstrated higher potency than thalidomide in the PluriBeat assay.
  • The assay provided quantitative data on the effects of tested compounds on EB beating and size.

Conclusions:

  • The PluriBeat assay represents a novel and effective in vitro method for predicting chemical adverse effects on embryonic development.
  • This assay holds promise for improving the prediction of human developmental toxicity, contributing to enhanced safety assessments.
  • The use of hiPSC-derived EBs offers a robust model for studying chemical impacts on early human development.