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

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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.