Development of hybrid artificial liver support system using spheroid culture and application to warm ischemic liver failure in dog and pig as a preclinical test

Abstract

We developed a hybrid artificial liver module of multi-capillary polyurethane foam (MC-PUF) packed-bed type for large animal experiments. Primary dog and porcine hepatocytes spontaneously formed spheroids in the module within 24 h. Furthermore, we developed an extracorporeal circulation system, including artificial liver module containing 3.0×10 9 cells (one module) and 6.4×10 9 cells (two modules) which were applied to warm ischemic liver failure dogs (15 kg) and a pig (25 kg), respectively. Consequently, blood glucose concentrations in the dogs and pig were well maintained, increases of blood ammonia concentration were suppressed by use of our artificial liver support system. And survival time of the pig was extended about 4 times more than the control experiments by applying the artificial liver support system. These results indicate that the MC-PUF packed-bed module including hepatocyte spheroids seems to be promising as a hybrid artificial liver support system.