Flow and nitric oxide increase hepatic function in co-culturing hepatocytes with hepatic stellate cells and endothelial cells

Abstract

It is necessary to develop the way how researchers culture hepatocytes (HC) for showing high levels of hepatic functions in vitro, because functions of HC in vitro is only 2-hundredth part of the functions in vivo. Hepatic function increased when HC were cultured within endothelial cells (EC) and hepatic stellate cells (HSC). Nitric oxide (NO) also increased hepatic function. However no study has described the effects of media flow load on a co-culture model of HC, HSC and EC. Furthermore there was no research on NO in co-culture model. Therefore, we developed co-culture models that include three of these cell types, and assayed their hepatic functions under flow. We also measured the NO concentration in each models. All models under load of flow exhibited high hepatic function than in static culture. Under load of flow, HC+HSC model and HC+HSC+EC model showed the highest hepatic function. In almost models NO concentration exhibited the same tendency to increase along with hepatic function. We suggested co-culture and flow influenced hepatic function, and NO related to the improvement of hepatic function. Furthermore, we thought HSC caused other elements of the improvement.