Drug-induced cytotoxicity prediction in muscle cells, an application of the Cell Painting assay

Roman Lambert ^1,2, Eva Serrano Candelas ², Pablo Aparicio ³

⁰University of Galway, School of Medicine, Pharmacology & Therapeutics, Galway, Ireland.

Plos One +

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March 31, 2025

View abstract on PubMed

Summary

This study uses Cell Painting with myoblast cells to predict chemical toxicity. Novel cell-based descriptors accurately forecast cellular viability and drug responses, reducing animal testing needs.

Area Of Science

Toxicology and computational biology
Cellular imaging and high-content screening

Background

In silico toxicity prediction aims to reduce animal testing by integrating experimental data with computational methods.
Cell Painting is a promising technique for toxicity prediction, but often uses cancer cells, limiting relevance for certain toxicological endpoints.
Developing more relevant cell models is crucial for improving the accuracy of computational toxicology.

Purpose Of The Study

To develop and validate a novel in silico toxicity prediction approach using a myoblast cell line.
To characterize cellular responses to known myotoxicants using Cell Painting.
To establish cell-based descriptors for predicting cytotoxicity and drug responses in muscle cells.

Main Methods

Utilized Cell Painting assay on a myoblast cell line (C2C12) exposed to 30 known myotoxicants.
Generated feature fingerprints describing cellular perturbations based on intensity, shape, and texture.
Employed computational analysis to correlate these descriptors with cellular viability and fate.

Main Results

Cell-based descriptors effectively predicted cellular viability and fate in both myoblasts and differentiated myotubes.
The approach enabled clustering of drugs based on their cytotoxicity profiles.
Demonstrated the utility of non-cancerous cell models for toxicity prediction.

Conclusions

Cell Painting combined with novel feature descriptors provides a robust method for in silico toxicity prediction in myoblasts.
This approach enhances the relevance of Cell Painting for myotoxicity assessment and reduces reliance on animal models.
The developed descriptors offer valuable insights into chemical-induced cellular responses and drug classification.