Hepatocyte transplantation using biodegradable matrices in ascorbic acid-deficient rats: Comparison with heterotopically transplanted liver grafts

Background Hepatocyte transplantation using polymeric matrices is under inv estigation as an alternative therapy for metabolic liver diseases. Long-ter m engraftment of hepatocytes in polymers has been demonstrated. However, th e 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 gl ycolic acid matrices seeded with hepatocytes equivalent to 20% of the recip ient's liver mass, or 20% liver grafts were heterotopically transplanted in to ascorbic acid- (AsA) deficient recipients. Recipients of cell-free matri ces or AsA-deficient liver grafts served as controls. Recipients were set o n AsA-free diet after transplantation. Plasma AsA levels, AsA concentration s in liver and adrenal gland tissue, and body weight ratios were assessed a nd 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 auxilia ry liver transplantation prevented symptoms of scurvy and increased plasma and tissue AsA levels and body weight ratios. AsA levels in recipients of 2 0% liver grafts were comparable to normal control animals, Conclusions. Hepatocytes transplanted in polymeric matrices are able to com pensate 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 param eters. Further research work is needed to increase the efficiency of liver cell transplantation with regard to a clinical application.