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Recombinant Human Hepatocyte Growth Factor Facilitates Biliary Transport After Hepatocyte Transplantation in Eisai Hyperbilirubinemic Rats

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Abstract

Hepatocyte transplantation may offer anattractive treatment for inborn errors of livermetabolism. However, factor(s) are required as stimulito induce proliferation of the limited number ofhepatocytes transplanted. The Eisai hyperbilirubinemic rat(EHBR) is a SpragueDawley (SD) mutant rat withconjugated hyperbilirubinemia. EHBRs have impairedcanalicular excretory transport of organic anions, bileacid glucuronide, and sulfate. Recombinant humanhepatocyte growth factor (rhHGF) (100 μg/kg) wasinjected intravenously at 2-hr intervals for 10 hr,immediately and 35 days following the intraportalinjection of 1 × 107 wild-type SD rathepatocytes. Serum bilirubin concentrations decreasedsignificantly within 35 days and were maintained atsignificantly reduced levels for 120 days followingtransplantation. Biliary excretion was demonstrated by the biliarytransport of indocyanine green and sulfobromophthaleinsodium into the bile. These results indicate thathepatic transport of bile acid conjugates in EHBRs can be restored by hepatocyte transplantationcombined with repeated administration of exogenousrhHGF, in conjunction with functioning of therecipient's excretory biliary system.

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Authors
  1. Yasuo Yamaguchi
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  2. Hiromitsu Hamaguchi
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  3. Shinwa Yamada
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  4. Kenji Fujiwara
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  5. Kanji Higashio
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  6. Nobutomo Miyanari
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  7. Osamu Ichiguchi
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  8. Mataro Goto
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  9. Katsutaka Mori
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  10. Michio Ogawa
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Yamaguchi, Y., Hamaguchi, H., Yamada, S. et al. Recombinant Human Hepatocyte Growth Factor Facilitates Biliary Transport After Hepatocyte Transplantation in Eisai Hyperbilirubinemic Rats. Dig Dis Sci 42, 522–528 (1997). https://doi.org/10.1023/A:1018886707487

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