Regenerative Medicine (2003) / Chapter Skim
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12 The origin and liver repopulating capacity of murine oval cells
12 The origin and liver repopulating capacity of murine oval cells
Pages 65-72
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From page 65... ...
The liver repopulating cells in these secondary transplant recipients lacked the genetic markers of the original bone marrow donor. We conclude that hepatic oval cells do not originate in bone marrow but in the liver itself, and that they have valuable properties for therapeutic liver repopulation.
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From page 66... ...
Several antibodies were used to determine the properties of cells involved in the oval cell/atypical duct proliferation. The mouse hepatic oval cell marker A6 (37)
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From page 67... ...
To further characterize the DDC-induced oval cells/atypical duct cells, we enriched them on a discontinuous Nycodenz density gradient (254. Nonparenchymal liver cells were isolated from mice after DDC treatment for 3-4 weeks and from controls.
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From page 68... ...
Next, we asked whether the oval/atypical duct cells observed in DDC-treated animals were of hepatocellular origin in viva. To determine whether oval cells originated from hepatocytes, animals with chimeric livers were generated, in which the hepatocytes and nonparenchymal cells were genetically distinct.
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From page 69... ...
This result suggested that DDC-induced oval cells were able to differentiate into fully functional hepatocytes and repopulate the Fah - / - liver. On the other hand, similar sized nonparenchymal cells from untreated normal liver were not capable of liver repopulation.
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From page 70... ...
The experiments showed that the oval cells induced by chronic administration of DDC neither derived from mature hepatocytes nor originated in significant proportions from progenitors in the bone marrow. Thus, our observations were most consistent with the classic model where preexisting intrahepatic stem cells/progenitors residing in the portal region are induced to become oval cells that then differentiate into hepatocytes.
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From page 71... ...
Surprisingly, however, no reports on liver repopulation by oval cells or functional rescue of a liver disease by oval cell transplantation have been reported (55~. It was therefore unclear whether the reported differentiation of adult oval cells into "hepatocytes" was functionally relevant and whether oval cells could serve as a source of transplantable, therapeutically effective hepatocyte precursors.
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From page 72... ...
23. Shafritz, D
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