Hybrid Artificial Liver with Polyurethane Foam / Spheroid Culture for Treatment of Acute Liver Failure

Abstract

We developed a new hybrid artificial liver (HAL) module including hepatocyte spheroids that formed in pores of polyurethane foam (PUF). The efficacy of our HAL was evaluated by applying to the liver failure pig in preclinical experiments. We designed a multi-capillary PUF (MC-PUF) module containing 1 x 10¹⁰ porcine hepatocytes. In a preclinical study, the PUF module was applied to a pig of 25 kg pig warm ischemic liver failure (HAL group, n=3). The same system without hepatocyte in the module was also applied to the liver failure pig as control (Control group, n=3).In the control group, the blood ammonia rapidly increased up to 1028 N-µg / dl in 12 h. On the other hand the increase in blood ammonia was suppressed below the hepatic coma level of 200 N-µg / dl in the HAL group. Curative effects such as maintenance of the fisher's ratio, blood gluconeogenesis, suppression of the increase of blood lactic acid, stabilization of the vital signs and urinary excretion were also observed in the HAL group. The average survival time in the HAL group was extended to 19.3 h from 8.9 h of that in the control group. In conclusion, we successfully developed the original HAL to be applicable to a treatment of a liver failure patient.