MULTICELLULAR HEPATOCYTE SPHEROIDS FOR DEVELOPMENT OF BIOARTIFICIAL LIVER SUPPORT SYSTEM AND DRUG METABOLISM STUDIES

A collagen entrapment hollow fiber bioreactor employing xenogeneic hepatocytes has been developed as a short term extracorporeal bioartificialliver (BAL) support for patients in acute liver failure. Scaling up the system requires large quantities of viable and highly active cells. Hepatocytes grown as spheroids manifest higher metabolic activities for longer time periods as compared to hepatocytes cultivated as single cell cultures. A method was developed for preparation of hepatocyte spheroids on a large scale. Porcine hepatocytes when cultured under stirred conditions, form multicellular spheroids in hormonally defmed culture medium within 24 hr with an efficiency of 8090%. Morphological studies show a resemblance between cells in the spheroids and in the liver in vivo. Specific liver functions of hepatocyte spheroids such as ureagenesis, albumin production and drug metabolism were enhanced for longer culture periods as