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Updated: Jun 12, 2025

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation

Published on: June 17, 2015

Morphometric-Assisted Prediction of Developmental Toxicity Using Stem Cell-Based Embryo Models in Microwells.

Vinidhra Shankar¹, Athanasia Zoi Pappa¹, Clemens van Blitterswijk¹

¹MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology-Inspired Tissue Engineering (cBITE), Maastricht University, Maastricht, 6229ET, The Netherlands.

Advanced Healthcare Materials

|May 10, 2025

Summary

This study introduces a novel stem cell model and automated platform to assess developmental toxicity. It reveals that certain compounds disrupt embryonic development by causing "morphotoxicity," even without impacting cell viability.

Keywords:

developmental and reproductive toxicity (DART)high throughput screening microwells stem cell‐based embryo models teratogens

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Last Updated: Jun 12, 2025

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Published on: June 17, 2015

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In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

Published on: May 11, 2021

Area of Science:

Developmental toxicology
Stem cell biology
High-throughput screening

Background:

Congenital abnormalities contribute significantly to fetal defects and mortality.
Animal studies face ethical and logistical constraints, driving the need for alternative models.
Existing in vitro models often lack complexity, automation, or real-time readouts.

Purpose of the Study:

To develop a scalable, automated platform for assessing chemical effects on early embryogenesis.
To introduce a novel embryo model, XEn/EpiCs, mimicking peri-implantation development.
To evaluate "morphotoxicity" as a complementary endpoint to cytotoxicity in developmental toxicity testing.

Main Methods:

Generation of a microwell-based embryo model (XEn/EpiCs) for co-development of extraembryonic endoderm and epiblast.
Utilizing a scalable, automated platform for imaging and quantifying morphological features.
Screening a library of 38 compounds to assess both cytotoxicity and morphotoxicity.

Main Results:

High doses of retinoic acid, caffeine, ampyrone, and dexamethasone significantly disrupted XEn/EpiC development.
Observed morphotoxic effects occurred independently of direct cytotoxicity in some cases.
The platform successfully quantified morphological changes indicative of developmental disruption.

Conclusions:

Morphotoxicity assessment provides crucial insights beyond traditional cytotoxicity assays.
This approach enhances the prediction of teratogenic risks from chemical exposures.
The developed platform and model offer a promising tool for developmental toxicity screening.