Recombinant human hepatocyte growth factor facilitates biliary transport after hepatocyte transplantation in Eisai hyperbilirubinemic rats.
Hepatocyte transplantation may offer an attractive treatment for inborn errors of liver metabolism. However, factor(s) are required as stimuli to induce proliferation of the limited number of hepatocytes transplanted. The Eisai hyperbilirubinemic rat (EHBR) is a Sprague-Dawley (SD) mutant rat with conjugated hyperbilirubinemia. EHBRs have impaired canalicular excretory transport of organic anions, bile acid glucuronide, and sulfate. Recombinant human hepatocyte growth factor (rhHGF) (100 microg/kg) was injected intravenously at 2-hr intervals for 10 hr, immediately and 35 days following the intraportal injection of 1 x 10(7) wild-type SD rat hepatocytes. Serum bilirubin concentrations decreased significantly within 35 days and were maintained at significantly reduced levels for 120 days following transplantation. Biliary excretion was demonstrated by the biliary transport of indocyanine green and sulfobromophthalein sodium into the bile. These results indicate that hepatic transport of bile acid conjugates in EHBRs can be restored by hepatocyte transplantation combined with repeated administration of exogenous rhHGF, in conjunction with functioning of the recipient's excretory biliary system.
Yamaguchi
Y
Y
Department of Surgery II, Kumamoto University Medical School, Japan.
Hamaguchi
H
H
Yamada
S
S
Fujiwara
K
K
Higashio
K
K
Miyanari
N
N
Ichiguchi
O
O
Goto
M
M
Mori
K
K
Ogawa
M
M
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D001692:Biological Transport / Q000187:drug effects; D004396:Coloring Agents / Q000493:pharmacokinetics; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006932:Hyperbilirubinemia / Q000378:metabolism*; D007202:Indicators and Reagents; D007208:Indocyanine Green / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D016031:Liver Transplantation / Q000379:methods / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013448:Sulfobromophthalein / Q000493:pharmacokinetics; D013997:Time Factors
D004396:Coloring Agents; D007202:Indicators and Reagents; D011994:Recombinant Proteins; D013448:Sulfobromophthalein; D017228:Hepatocyte Growth Factor; D007208:Indocyanine Green; D001663:Bilirubin