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¶
From the Marion Bessin Liver Research Center,*
the
Division of Gastroenterology, Hepatology, and
Nutrition,
and the Departments of
Medicine,
Cell
Biology,
and Pathology,¶
Albert Einstein College of Medicine, Bronx, New York
The potential of embryonal day (ED) 14 fetal liver epithelial
progenitor (FLEP) cells from Fischer (F)344 rats to repopulate the
normal and retrorsine-treated liver was studied throughout a 6-month
period in syngeneic dipeptidyl peptidase IV (DPPIV-)
mutant F344 rats. In normal liver, FLEP cells formed: 1)
hepatocytic clusters ranging in size up to 
800 to 1000 cells; 2)
bile duct structures connected to pre-existing host bile ducts; and 3)
mixed clusters containing both hepatocytes and bile duct epithelial
cells. Liver repopulation after 6 months was moderate (5 to 10%). In
retrorsine-treated liver, transplanted cells formed large
multilobular structures containing both parenchymal and bile duct cells
and liver repopulation was extensive (60 to 80%). When the
repopulating capacity of ED 14 FLEP cells transplanted into normal
liver was compared to adult hepatocytes, three important
differences were noted: 1) FLEP cells continued to proliferate at
6 months after transplantation, whereas adult hepatocytes
ceased proliferation within the first month; 2) both the number and
size of clusters derived from FLEP cells gradually increased throughout
time but decreased throughout time with transplanted mature
hepatocytes; and 3) FLEP cells differentiated into hepatocytes when
engrafted into the liver parenchyma and into bile epithelial cells when
engrafted in the vicinity of the host bile ducts, whereas adult
hepatocytes did not form bile duct structures. Finally, after
transplantation of ED 14 FLEP cells, new clusters of
DPPIV+ cells appeared after 4 to 6 months,
suggesting reseeding of the liver by transplanted cells. This study
represents the first report with an isolated fetal liver epithelial
cell fraction in which the cells exhibit properties of
tissue-determined stem cells after their transplantation into normal
adult liver; namely, bipotency and continued proliferation long
after their transplantation.
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