Development of a bioartificial liver: Properties and function of a hollow-fiber module inoculated with liver cells

TLDR

The study developed a mathematical model of mass transport in a hollow‑fiber bioartificial liver module across different plasma flow rates and configurations. Liver cells were isolated via portal‑vein perfusion with EDTA or EDTA/collagenase, cultured in a hollow‑fiber bioreactor, and the system was tested in a reproducible large‑animal model of acute ischemic liver failure, with a mass‑transport mathematical model developed for various flow rates and configurations. In vitro and in vivo studies demonstrated that the bioartificial liver performed differentiated metabolic functions, isolated cyclosporine and testosterone metabolites, lowered serum ammonia and lactate, raised glucose and systolic blood pressure, and maintained >90 % cell viability after 6 h treatment. Published in Hepatology 1993;17:258‑265.

Abstract

We have developed a bioartificial liver support system utilizing hollow-fiber bioreactor, plasmapheresis and microcarrier cell culture technologies. Liver cells were obtained through portal vein perfusion with ethylenediaminetetraacetate or ethylenediaminetetraacetate/collagenase. A mathematical model of mass transport in a hollow-fiber module, at various plasma flow velocities and system configurations, was developed. The bioartificial liver's ability to carry out specific differentiated metabolic liver functions was tested in vitro and in vivo . A reproducible large-animal model of acute ischemic liver failure was developed. Most major first-generation cyclosporine and 19- nor terstosterone metabolites were isolated after substrate addition to the bioartificial liver in vitro . After bioartificial liver treatment for 6 hr (with dog or pig liver cells), dogs with acute liver failure had significantly lower serum ammonia and lactate levels and significantly higher serum glucose levels than did control animals treated with a bioartificial liver system inoculated with microcarriers alone. In addition, bioartificial liver-treated animals had significantly higher mean systolic blood pressures than did controls. Liver cell viability at the end of the 6-hr in vivo experiment was greater than 90%. (Hepatology 1993;17:258-265.)