Stem cell properties and repopulation of the rat liver by fetal liver epithelial progenitor cells

The potential of embryonal day (ED) 14 fetal liver epithelial progenitor (F LEP) cells from Fischer (F)344 rats to repopulate the normal and retrorsine -treated liver was studied throughout a 6-month period in syngeneic dipepti dyl peptidase IV (DPPIV-) mutant F344 rats. in normal liver, FLEP cells for med: 1) hepatocytic clusters ranging in size up to similar to 800 to 1000 c ells, 2) bile duct structures connected to pre-existing host bile ducts; an d 3) mixed clusters containing both hepatocytes. and bile duct epithelial c ells. Liver repopulation after 6 months was moderate (5 to 10%). In retrors ine-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 t ransplanted into normal liver was compared to adult hepatocytes, three impo rtant differences were noted: 1) FLEP cells continued to proliferate at 6 m onths after transplantation, whereas adult hepatocytes ceased proliferation within the first month; 2) both the number and size of clusters derived fr om 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 ep ithelial cells when engrafted in the vicinity of the host bile ducts, where as adult hepatocytes did not form bile duct structures. Finally, after tran splantation of ED 14 FLEP cells, new dusters of DPPIV+ cells appeared after 4 to 6 months, suggesting reseeding of the liver by transplanted cells. Th is study represents the first report with an isolated fetal liver epithelia l cell fraction in which the cells exhibit properties of tissue-determined stem cells after their transplantation into normal adult liver; namely, bip otency and continued proliferation long after their transplantation.