Hepatocytes buried in the cirrhotic livers of patients with biliary atresia proliferate and function in the livers of urokinase-type plasminogen activator–NOG mice

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書誌事項

公開日
2014-09
資源種別
journal article
権利情報
  • http://creativecommons.org/licenses/by-nc-nd/3.0/
  • http://doi.wiley.com/10.1002/tdm_license_1.1
DOI
  • 10.1002/lt.23916
公開者
Ovid Technologies (Wolters Kluwer Health)

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説明

<jats:sec> <jats:title/> <jats:p>The pathogenesis of biliary atresia (BA), which leads to end-stage cirrhosis in most patients, has been thought to inflame and obstruct the intrahepatic and extrahepatic bile ducts. BA is not believed to be caused by abnormalities in parenchymal hepatocytes. However, there has been no report of a detailed analysis of hepatocytes buried in the cirrhotic livers of patients with BA. Therefore, we evaluated the proliferative potential of these hepatocytes in immunodeficient, liver-injured mice [the urokinase-type plasminogen activator (uPA) transgenic NOD/Shi-scid IL2rγnull (NOG); uPA-NOG strain]. We succeeded in isolating viable hepatocytes from the livers of patients with BA who had various degrees of fibrosis. The isolated hepatocytes were intrasplenically transplanted into the livers of uPA-NOG mice. The hepatocytes of only 3 of the 9 BA patients secreted detectable amounts of human albumin in sera when they were transplanted into mice. However, human leukocyte antigen–positive hepatocyte colonies were detected in 7 of the 9 mice with hepatocyte transplants from patients with BA. We demonstrated that hepatocytes buried in the cirrhotic livers of patients with BA retained their proliferative potential. A liver that was reconstituted with hepatocytes from patients with BA was shown to be a functioning human liver with a drug-metabolizing enzyme gene expression pattern that was representative of mature human liver and biliary function, as ascertained by fluorescent dye excretion into the bile canaliculi. These results imply that removing the primary etiology via an earlier portoenterostomy may increase the quantity of functionally intact hepatocytes remaining in a cirrhotic liver and may contribute to improved outcomes. <jats:italic toggle="yes">Liver Transpl 20:1127–1137, 2014</jats:italic>. © 2014 AASLD.</jats:p> </jats:sec>

収録刊行物

  • Liver Transplantation

    Liver Transplantation 20 (9), 1127-1137, 2014-09

    Ovid Technologies (Wolters Kluwer Health)

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