High-Content Cytotoxicity Screening by iPSC-Derived Hepatocytes

4 High-Content Cytotoxicity Screening by iPSC-Derived Hepatocytes 

As mentioned above, cytotoxicity evaluation is one of the applications on iPSC-derived disease models [104]. With the use of a high-content assay, a series of readouts, such as cell viability, nuclear shape, average and integrated cell area, mitochondrial membrane potential, phospholipid accumulation, cytoskeleton integrity, and apoptosis, have been examined as a general and mechanism-specific hepatotoxicity. In this particular application, the cell model for the assay 

Besides multiple staining protocols, a mitochondria potential assay was applied to further assess the toxicity, which was able to rapidly measure the effect of compound on mitochondria potential. After cells were treated with compounds for 60 min, the mitochondria-active dye JC-10 was added for 15-30 min incubation with reagents. In addition, the assay was able to test the effects on inducing autophagy and phospholipidosis after treating the cell with compounds for 24 and 48 h, respectively. The method is compatible for screening of hundreds of compounds within 72 h. 

1 Hopkins, AX. and Groom, C.R. (2002) The druggable genome. Nature Reviews Drug Discovery, 1, 727-730. 

Paslay, J.W., Schopfer, U., and Sittampalam, G.S. (2011) Impact of high-throughput screening in biomedical research. Nature Reviews Drug Discovery, 10, 188-195. 

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