Citations : High-Content Assay Multiplexing for Muscle Toxicity Screening in Human-Induced Pluripotent Stem Cell-Derived Skeletal Myoblasts

Dated: Sep 01, 2018

Publication Name: Assay and Drug Development Technologies

This study set out to develop a high-throughput multiplexed assay using iPSC-derived skeletal myoblasts that can be used as a first-pass screen to assess the potential for chemicals to affect skeletal muscle. We found that cytotoxicity and cytoskeletal integrity are most useful and reproducible assays for the skeletal myoblasts when evaluating overall cellular health or gauging disruptions in actin polymerization following 24 h of exposure. Both assays are based on high-content imaging and quantitative image processing to derive quantitative phenotypes. Both assays showed good to excellent assay robustness and reproducibility measured by interplate and interday replicability, coefficients of variation of negative controls, and Z′-factors for positive control chemicals. Concentration response assessment of muscle-related toxicants showed specificity of the observed effects compared to the general cytotoxicity. Overall, this study establishes a high-throughput multiplexed assay using skeletal myoblasts that may be used for screening and prioritization of chemicals for more complex tissue chip-based and in vivo evaluation.

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Contributors: William D. Klaren and Ivan Rusyn