title: Effects of plasma from patients with fulminant hepatic failure on function of primary rat hepatocytes in three-dimensional culture.
abstract: OBJECTIVE
  As biotechnology continues to advance, a bioartificial liver is expected to be developed for the treatment of patients with fulminant hepatic failure (FHF) whose liver dysfunction is potentially reversible or for providing liver support as a bridge to liver transplantation. While monolayer-cultured hepatocytes rapidly lose their capacity to express many liver-specific functions over time when cultured, spherical-shaped hepatocytes in three-dimensional culture with the use of extracellular matrix components sustain long-term survival by maintaining differentiated hepatocyte functions. The aim of this study was to investigate whether sufficient functions of viable spherical-shaped hepatocytes could be maintained in plasma of patients with FHF in order to use these cells in an extracorporeal system.
  
  
  METHODS
  Hepatocyte functions were evaluated under monolayer or three-dimensional culture in FHF plasma.
  
  
  RESULTS
  Primary rat hepatocytes on poly-N-p-vinylbenzyl-D-lactonamide (PVLA) formed spheroids even in FHF plasma and maintained their spherical shapes in FHF plasma as long as in medium. Spherical-shaped hepatocytes on PVLA cultured in FHF plasma showed higher activity in albumin secretion, urea formation, and gluconeogenesis than those in normal human plasma or medium. As being cultured in medium, hepatocytes on PVLA cultured in plasma were also superior to cells on collagen in regard to albumin secretion, amino acid metabolism, and gluconeogenesis.
  
  
  CONCLUSIONS
  These findings demonstrated that FHF plasma is not toxic to rat hepatocyte spheroids and that hepatocyte spheroids have potential use in the development of a bioartificial liver.
authors.affiliation: First Department of Internal Medicine, Gifu University School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan. mnagaki@cc.gifu-u.ac.jp
authors.forename: Masahito
authors.initials: M
authors.lastname: Nagaki
authors.forename: Tomoo
authors.initials: T
authors.lastname: Naito
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akaike
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Muto
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
mesh_terms: D000418:Albumins / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005943:Gluconeogenesis; D022781:Hepatocytes / Q000502:physiology*; D017114:Liver Failure, Acute / Q000097:blood*; D008297:Male; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000378:metabolism
chemical_list: D000418:Albumins; D000596:Amino Acids; D014508:Urea