Developmental Neurotoxicity Risk Assessment Using iPSC-Derived 3D NPC Spheroids

OECD Developmental Neurotoxicity (DNT) work group designed a cell migration assay using neuroprecursor cell (NPC) differentiation. Through differentiating into glial cells, multiple parameters are extracted to assess DNT risk. Here we demonstrate our hands-on results for DNT risk assessment to pesticide compounds.

3D spheroids were formed from iPSC-derived NPCs as shown above.

Quantitative parameters were extracted from these immunocyte chemistry images.

This barchart shows responses of area sizes of spheroids to pesticides as well as positive and negative compounds

All parameters were extracted and summarized as heatmaps above.

The heatmap parameters are used to create a principal component analysis (PCA) above. Medium risk is detected with 1~2x of the SD of negative controls. High risk is detected with 2x of the SD.

Unpublished data

References:

• "Initial Recommendations on Evaluation of Data from the Developmental Neurotoxicity (DNT) In-Vitro Testing Battery" approved by WNT in April 2023 and published on the 4th of July 2023  (https://one.oecd.org/document/ENV/CBC/MON(2023)13/en/pdf）

• OECD DNT website (https://www.oecd.org/en/topics/sub-issues/testing-of-chemicals/in-vitro-assays-for-developmental-neurotoxicity.html)