Long term human primary hepatocyte cultures in a microfluidic liver biochip show maintenance of mRNA levels and higher drugs metabolisms when compared to Petri cultures

Abstract We have cultivated, for 13 days, human primary hepatocytes in a microfluidic bioreactor and in Petri. mRNA kinetics have shown in biochips an increase of the levels of CYP2B6, CYP2C19, CYP2C8, CYP3A4, CYP1A2, CYP2D6, HNF4a, SULT1A1, UGT1A1 mRNA related genes when compared to post extraction levels. In addition, comparison with Petri have shown a higher levels of CYP2B6, CYP2C19, CYP2C8, CYP3A4, CYP1A2, CYP2D6 related genes at the end of cultures. Functional assays illustrated a higher urea and albumin production over the period of culture in biochips. Bioreactor drug metabolism (midazolam and phenacetin) was not superior to Petri one after 2 days of culture. Then CYP3A4 midazolam metabolism was maintained in biochip after 13 days of culture whereas it was almost not detected in Petri. This leads to reach up to 5000‐fold higher value in biochip of our metabolic ratio. CYP1A2 phenacetin metabolism was found higher in biochips after 5, 9 and 13 days of culture. Thus, a 100‐fold higher metabolic ratio of APAP in biochips was measured after 13 days of perfusion. These results demonstrated functional primary human hepatocyte cultures in the bioreactor in the case of long‐term culture.
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: Original Paper Source Type: research