Hepatocyte transplantation using biodegradable matrices in ascorbic acid-deficient rats: comparison with heterotopically transplanted liver grafts.
BACKGROUND
Hepatocyte transplantation using polymeric matrices is under investigation as an alternative therapy for metabolic liver diseases. Long-term engraftment of hepatocytes in polymers has been demonstrated. However, the metabolic activity of hepatocytes in such devices has never been assessed in direct comparison with liver grafts.


METHODS
Hepatocyte and partial liver transplantation were evaluated in the scurvy-prone osteogenic disorder Shionogi rat model. Biodegradable poly glycolic acid matrices seeded with hepatocytes equivalent to 20% of the recipient's liver mass, or 20% liver grafts were heterotopically transplanted into ascorbic acid- (AsA) deficient recipients. Recipients of cell-free matrices or AsA-deficient liver grafts served as controls. Recipients were set on AsA-free diet after transplantation. Plasma AsA levels, AsA concentrations in liver and adrenal gland tissue, and body weight ratios were assessed and H&E histology was performed.


RESULTS
Recipients from the control groups showed symptoms of scurvy at 1 month after cessation of AsA supply. Hepatocyte transplantation and auxiliary liver transplantation prevented symptoms of scurvy and increased plasma and tissue AsA levels and body weight ratios. AsA levels in recipients of 20% liver grafts were comparable to normal control animals.


CONCLUSIONS
Hepatocytes transplanted in polymeric matrices are able to compensate for liver-based metabolic deficiencies. Hepatocyte transplantation improves plasma AsA levels in AsA-deficient recipients. However, auxiliary liver grafts are superior to hepatocyte grafts in improving metabolic parameters. Further research work is needed to increase the efficiency of liver cell transplantation with regard to a clinical application.
Uyama
S
S
Department of Hepatobiliary Surgery, University of Hamburg Medical Center, Germany.
Kaufmann
P M
PM
Kneser
U
U
Fiegel
H C
HC
Pollok
J M
JM
Kluth
D
D
Vacanti
J P
JP
Rogiers
X
X
D000818:Animals; D001206:Ascorbic Acid Deficiency / Q000378:metabolism; D001672:Biocompatible Materials / Q000008:administration & dosage; D001673:Biodegradation, Environmental; D022781:Hepatocytes / Q000637:transplantation*; D016031:Liver Transplantation; D008297:Male; D023421:Models, Animal; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D016042:Transplantation, Heterotopic
D001672:Biocompatible Materials