IMPROVEMENT OF SERUM AMINO-ACID PROFILE IN HEPATIC-FAILURE WITH THE BIOARTIFICIAL LIVER USING MULTICELLULAR HEPATOCYTE SPHEROIDS

We designed a bioartificial liver support system in which encapsulated multicellular spheroids of rat hepatocytes were utilized as a bioreac tor in a hollow fiber cartridge. The spheroids, formed in a positively charged polystyrene dish that contained hormonally defined medium, we re encapsulated into microdroplets of agarose that contained about 9 x 10(7) rat hepatocytes. The medium, including 150 mt reservoir volume, was circulated in a closed circuit in which the cartridge was inserte d. The pH and levels of dissolved oxygen were monitored and automatica lly regulated so that they were maintained within a constant range for 72 h. Albumin accumulated in the circuit at the rate of 2.0 mg/L/h in this system. When the bioreactor cells in the system were replaced wi th Hep G2 cells, a human hepatoblastoma cell line, albumin accumulated at the rate of 0.15 mg/L/h. The spheroids of primary culture hepatocy tes had 13 times higher albumin-producing capacity than the aggregates of Hep G2. The serum of a patient with fulminant hepatic failure was circulated in this system with the spheroids of primary culture hepato cytes. The concentration of branched amino acid (BCAA) in the circuit significantly increased during the 48 h circulation, while the concent ration of aromatic amino acid (AAA) and methionine decreased. The rati o of BCAA/AAA increased from 0.640 to 0.772, indicating that the hepat ocyte spheroids had improved the imbalance of the amino acid profile i n the serum. These findings indicate that this system may be a useful model for an artificial liver support. (C) 1996 John Wiley & Sons, Inc .