Low-dose recombinant human hepatocyte growth factor enhances effect of hepatocyte transplantation in rats treated with retrorsine

Hepatogastroenterology. 2009 Sep-Oct;56(94-95):1466-70.

Abstract

Background/aims: The aim of this study was to regenerate transplanted hepatocytes selectively in a recipient using retrorsine and recombinant human hepatocyte growth factor (rhHGF).

Methodology: Nagase analbuminemic rats (NARs) received pretreatment with retrosine and were divided into three experimental groups. Group1: Hepatocyte transplantation (HcTx) + 50 microg/kg/day rhHGF. Group2: HcTx + 250 microg/kg/day rhHGF. Group3: HcTx + normal saline. The serum levels of albumin and the albumin-positive hepatocytes in the liver were investigated. The rat endogenous HGF of the rats given only retrorsine was measured.

Results: The serum albumin levels of Group11 were higher than those of Group2, while there was no significant difference between Group2 and GroupS. Histological examination of Group1 and 3 showed the presence of a large number of albumin-positive hepatocytes, which frequently consisted of large clusters and occupied 53.90 +/- 2.31% and 31.25 +/- 5.36% of host liver, respectively. The liver sections of Group2 showed numerous albumin-positive hepatocyte, which were not seen as clusters. The rat endogenous HGF concentration was extremely high.

Conclusion: Low-dose rhHGF enhances the effect of HcTx under the suppressive state of proliferation of host hepatocytes. Because of the high endogenous HGF, the administration of a high concentration of rhHGF suppressed the regenerative activity of the transplanted hepatocytes.

MeSH terms

  • Animals
  • Hepatocyte Growth Factor / blood
  • Hepatocyte Growth Factor / pharmacology*
  • Hepatocytes / transplantation*
  • Humans
  • Male
  • Pyrrolizidine Alkaloids / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Serum Albumin / analysis

Substances

  • Pyrrolizidine Alkaloids
  • Recombinant Proteins
  • Serum Albumin
  • Hepatocyte Growth Factor
  • retrorsine