Hepatocyte Spheroids in Polyurethane Foams: Functional Analysis and Application for a Hybrid Artificial Liver

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Abstract
Spherical multicellular aggregates (spheroids) of adult rat hepatocytes were spontaneously formed in the pores of polyurethane foam (PUF) as a culture substratum. Highly differentiated functions of hepatocytes, that is, albumin secretion, urea synthesis, and drug metabolism, were maintained in the spheroid culture using PUF. These spheroids were partly attached and immobilized in the pores of PUF. Then, we designed a PUF/spheroids packed-bed module as a hybrid artificial liver and developed an artificial liver support system, including an extracorporeal circulation line for recovery of a hepatic failure rat induced by D-galactosamine. Consequently, increases in blood ammonia concentrations in hepatic failure rats were suppressed below the hepatic coma level by the artificial liver support system, and 80% of these rats recovered from hepatic failure. From these results, it was suggested that hepatocytes/spheroid culture seemed to provide a promising culture system as a hybrid artificial liver.