[Cell culture model for hepatocyte culture in bioreactors for metabolic utilization in hybrid liver support system]

Hybrid systems with hepatocyte cultures in bioreactors are in development for therapeutical liver assistance. Here, a culture model with a special bioreactor construction was developed: Capillary membrane systems create a three dimensional artificial framework for hepatocyte adhesion, aggregation and reorganization of tissue structures. Many of small parallel capillary membrane units perfuse a few hepatocytes. Different capillary materials enable different functions. Cell perfusion between independent plasma inflow and outflow capillaries, independent oxygen supply and carbon dioxide removal as well as a co- culture with sinusoidal endothelial cells are possible. An in vitro study with bioreactors (n = 9), containing 2.5 x 10(9) pig hepatocytes was performed, measuring external metabolism of the cells: cytochrome P450-activity (midazolam metabolism, lidocaine/MEGX-test), synthesis (albumin), liver function test (galactose elimination) and cell alteration (LDH, GOT, GLDH, GPT, gamma GT) were investigated. The results demonstrate that external function of primary hepatocytes can be maintained over a period of at least three weeks.