Low-dose recombinant human hepatocyte growth factor enhances effect of hepatocyte transplantation in rats treated with retrorsine.
OBJECTIVE
The aim of this study was to regenerate transplanted hepatocytes selectively in a recipient using retrorsine and recombinant human hepatocyte growth factor (rhHGF).


METHODS
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.


CONCLUSIONS
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.
Hamada
Takayuki
T
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Eguchi
Susumu
S
Takatsuki
Mitsuhisa
M
Yamanouchi
Kosho
K
Sugiyama
Nozomu
N
Kawashita
Yujo
Y
Okudaira
Sadayuki
S
Tajima
Yoshitsugu
Y
Ishii
Takehisa
T
Kanematsu
Takashi
T
D000818:Animals; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000494:pharmacology*; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D008297:Male; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012709:Serum Albumin / Q000032:analysis
D011763:Pyrrolizidine Alkaloids; D011994:Recombinant Proteins; D012709:Serum Albumin; D017228:Hepatocyte Growth Factor; C003300:retrorsine