Assessment of the bioartificial liver support system that consisted of encapsulated multicellular spheroids of rat hepatocyte and a hollow fiber cartridge

We designed the hollow fiber type bio-artificial liver support system in which encapsulated multicellular spheroids were utilized as a bioreactor. Multicellular spheroids of rat hepatocyte were encapsulated into microdroplets of agarose. The microdroplets containing 9x10⁷ rat hepatocyte were packed into the extra capillary space of a hollow fiber cartridge. Hormonal defined medium, 150ml including reservoir volume, was circulated in a closed circuit in which the cartridge was inserted. The levels of dissolved oxygen and pH were monitored and were automatically regulated to maintain at a constant range for 7Z hours. Albumin was accumulated in the circuit at a rate of 2.0 mg/l/hour and transferrin was at a rate of 0.84 mg/l/hour until 24 hours. The spheroids were 86% viable after the circulating culture period. These results indicate that the system described in this paper is one of useful prototype modules to develop a bio-artificial liver support.