Extracorporeal liver system

Patients with fulminant hepatic failure waiting for liver transplantation would benefit greatly if they could receive liver support for the time it takes for a donor liver to arrive. Reported attempts to establish extracorporeal liver support have been based on bioreactors made up of only hepatocytes. Until now none of these reported models of liver bioreactors have been able to support animals with fulminant hepatic failure with satisfactorily results. Our knowledge about the function of the different types of liver cells dictates that the hepatocytes are mainly responsible for the biosynthesis of macromolecules and bile constituents, whereas sinusoidal cells like Kupffer cells and SEC monitor the blood and eliminate waste material. Therefore, to fullfill these tasks a bioreactor must contain both hepatocytes and sinusoidal cells. Kupffer cells are easily activated to produce reactive molecules that are toxic to other cells. Such metabolites are generated by SEC to a significantly lower degree. On this background we are currently working to establish a liver bioreactor consisting of hepatocytes and SEC. We have succeeded in establishing pure cultures of these cell types from piglet liver, and are currently working out optimal conditions to maintain the physiologic functions of the cells in vitro. The next step will be to bring isolated hepatocytes and sinusoidal SEC together into a specially designed container through which blood from experimental animals can be conducted.