RECOMBINANT HUMAN HEPATOCYTE GROWTH-FACTOR FACILITATES BILIARY TRANSPORT AFTER HEPATOCYTE TRANSPLANTATION IN EISAI HYPERBILIRUBINEMIC RATS

Hepatocyte transplantation may offer an attractive treatment for inbor n errors of liver metabolism. However, factor(s) are required as stimu li to induce proliferation of the limited number of hepatocytes transp lanted. The Eisai hyperbilirubinemic rat (EHBR) is a Sprague-Dawley (S D) mutant rat with conjugated hyperbilirubinemia. EHBRs have impaired canalicular excretory transport of organic anions, bile acid glucuroni de, and sulfate. Recombinant human hepatocyte growth factor (rhHGF) (1 00 mu g/kg) was injected intravenously at 2-hr intervals for 10 hr, im mediately and 35 days following the intraportal injection of 1 x 10(7) wild-type SD rat hepatocytes. Serum bilirubin concentrations decrease d significantly within 35 days and were maintained at significantly re duced levels for 120 days following transplantation. Biliary excretion was demonstrated by the biliary transport of indocyanine green and su lfobromophthalein sodium into the bile. These results indicate that he patic transport of bile acid conjugates in EHBRs can be restored by he patocyte transplantation combined with repeated administration of exog enous rhHGF, in conjunction with functioning of the recipient's excret ory biliary system.