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Microarray bioprinting technology has been explored to create miniaturized 3D cell cultures on a 384-pillar plate, which were combined with drug metabolizing enzymes (DMEs) and test compounds in a 384-well plate for metabolism-induced toxicity assays. Our goal in this study was to demonstrate rapid assessment of metabolism- induced toxicity on the 384-pillar plate and obtain reliable and highly predictive information on compound's hepatotoxicity in vivo. Briefly, human cells including Hep3B human hepatoma cell line as well as human embryonic kidney 293 (HEK 293) cell were encapsulated in alginate-Matrigel on the 384-pillar plate. Test compounds and six different DMEs including cytochromes P450 (CYP450) and UDP-glucuronosyltransferase (UGT) were dispensed in the 384-well plate. By sandwiching the 384-pillar plate onto the 384-well plate, human cells were exposed to the compounds and their metabolites generated by DMEs. The cells were stained with luminescent and fluorescent dyes and IC50 values were calculated using the luminescence and fluorescence obtained. In summary, our approach allowed us to assess mechanisms of metabolism-induced toxicity in high throughput. Thus, the 384- pillar plate could be used as a high-throughput, early stage, microscale alternative to conventional in vitro multi-well plate platforms and provide a rapid and inexpensive assessment of metabolism-induced toxicity at early phases of drug development.
Washkewicz College of Engineering
Chem & Biom Eng
Sickar, Yana; Kang, Soo-Yeon; Joshi, Pranav; and Yu, Kyeong-Nam, "P1: Assessment of Metabolism-Induced Hepatotoxicity on a 384-Pillar Plate" (2017). Undergraduate Research Posters 2017. 54.