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Development of a bioartificial liver: Properties and function of a hollow‐fiber module inoculated with liver cells
Author(s) -
Rozga Jacek,
Williams Frederick,
Ro ManSoo,
Neuzil Daniel F.,
Giorgio Todd D.,
Backfisch Gisela,
Moscioni Albert D.,
Hakim Raymond,
Demetriou Achilles A.
Publication year - 1993
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840170216
Subject(s) - bioartificial liver device , in vivo , microcarrier , collagenase , liver function , medicine , chemistry , in vitro , cell , biology , hepatocyte , biochemistry , enzyme , microbiology and biotechnology
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%. (H EPATOLOGY 1993;17:258–265.)