BioProject

Primary hepatocytes have been widely explored as cell sources for the study of in vitro drug metabolism and pharmacokinetics (DMPK). More...

Primary hepatocytes have been widely explored as cell sources for the study of in vitro drug metabolism and pharmacokinetics (DMPK). Aiming toward establishing an in vitro drug screening method, the current study illustrated a comprehensive increase in the DMPK-related gene expression of nanopillar (NP)-cultured 3D-spheroid. To examine the expressional changes in DMPK-related genes under four different conditions, namely, NP-, sandwich (SW)-, monolayer (ML)-cultured rat hepatocytes, and freshly isolated hepatocytes, genome-wide gene-expression analysis using a DNA microarray was performed. Among the DMPK-related genes, cytochrome P450, UDP-glucuronosyltransferase, and transporter genes were focused on. Principal component analysis showed that the global gene expression profile in sample from NP culture is closer to that from freshly isolated hepatocytes than that from SW culture. The expressions of almost all Cyp 1 to 3 and Ugt genes of NP-cultured 3-D spheroid were higher than those of ML and SW. The expression of Abcc2 gene whose translation product has a critical role in excretion of metabolized bile acids in hepatocyte to bile canaliculi was three times higher in NP than in ML. From these results, 3-D spheroid formed by the NP culture was suggested to possess higher ability of metabolism and excretion than conventional 2-D monolayer culture. The NP culture has a potential as an alternative culturing technique for evaluating metabolism and toxicity toward the development of new drugs. Overall design: Gene expression in rat hepatocyte was measured under four different conditions, namely, Nanopillar (NP)-, sandwich (SW)-, monolayer (ML)-cultured rat hepatocytes, and freshly isolated hepatocytes. Three independent experiments were performed at 95 hours of post-seeding. Less...