Recreating fetal development in vitro to identify drugs that may cause birth defects

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Researchers from the Institute of Bioengineering and Nanotechnology (IBM) in Singapore have successfully identified and recreated two key processes that underpin embryonic development in vitro, which could potentially enable toxicity testing of teratogenic compounds on fetal cells.

Published in Scientific Reports, the team were able to control the differentiation of embryonic stem cells into a given cell type but more importantly, they were also able to demonstrate the migration of these transformed cells, which has remained elusive until now. With this, an improved embryonic development model can be established in order to evaluate and identify the impact and mechanisms of certain drugs that can cause birth defects or miscarriages.

Embryonic stem cells

“Our breakthrough is a major step toward identifying such compounds and understanding how they affect embryonic growth, and we hope that it will eventually help to mitigate the risk of fetal exposure to these destructive agents.” – Professor Jackie Y. Ying, IBN Executive Director.

The current model for testing the effects of teratogens, compounds causing malformation in embryos, involves animal testing. These have proven ineffective due to cost, time-constraints and low reliability. Human pluripotent stem cells (hPSCs) present an alternative option that could alleviate the constraints presented by animal testing.

Utilizing their approach to control and restrict cell migration, the IBN researchers were able to generate a circular ring structure of mesoendoderm cells. The effects of teratogens can be ascertained by observing any changes to this ring structure. IBN Group Leader Professor Yu described the technique as “a reliable starting point and straightforward indicator for measuring drug-induced effects”.

Through image processing and statistical algorithms, the researchers were able to quantify and classify the teratogenic potential of different compounds. Using their micropatterned hPSC model, they have successfully distinguished between teratogenic compounds and non-teratogenic compounds as well as potentially measuring dose-dependent effects, which is essential for identifying a teratogenic agent’s clinically relevant dose.

The team hope to further develop and validate their technology through clinical and industrial partnerships.

– Mudith Jayawardana

Source: Recreating embryonic development ‘in a dish’ to study drugs that cause birth defects. Press Release
J. Xing, Y.-C. Toh, S. Xu and H. Yu. A method for human teratogenic detection by geometrically confined cell differentiation and migration. Scientific Reports, 5 (2015) 10038. DOI