Effect of Flow Load on Hepatic Function in Co-Culture of Hepatocytes with Hepatic Stellate Cells and Endothelial Cells: Relationship between Hepatic Function and Nitric Oxide Concentration in vitro

Abstract

To date, no study has described the effects of media flow load on a co-culture model of hepatocytes (HC), hepatic stellate cells (HSC) and endothelial cells (EC). Furthermore, no research has been reported regarding the influence of nitric oxide (NO) concentration in such a co-culture model. Therefore, we developed co-culture models that include two or three of these cell types, and assayed their hepatic functions both in static culture and under flow load. We also measured the NO concentration in each models and inhibited NO production of cells. In static culture, the HC+HSC and HC+HSC+EC models demonstrated higher hepatic function than in the model containing HC alone. Under flow load, all models exhibited higher hepatic function than in static culture. The HC+HSC and HC+HSC+EC models under flow demonstrated the highest hepatic function observed under any condition. In almost all models, NO concentration exhibited the same tendency to increase along with hepatic function, and NO improved hepatic function in vitro without in HC+HSC model under flow load. Inhibition of NO production decreased small levels of hepatic function in HC+HSC and HC+HSC+EC models under flow load. We conclude that co-culture and flow load positively impact hepatic function, and that HSC and NO are related to improvements in hepatic function. Furthermore, we consider that the presence of HSC is responsible for other aspects of improvement in hepatic function.

Keywords

• hepatocytes
• hepatic stellate cells
• endothelial cells
• co-culture
• flow load
• nitric oxide