Cell proliferation and renewal of normal hepatocytes and bile duct cells in adult mouse liver

BACKGROUND/AIMS: The source of new cells in the normal adult liver has been controversial. Some investigators have hypothesized the streaming liver model. On the other hand, others reject this hypothesis. We examined hepatic cell kinetics by a special labeling method with 3Hthymidine. METHODS: ICR mice received 112 repeated injections of 3Hthymidine at 6 h intervals for 28 days after birth and were killed immediately thereafter, or 100, 200 or 300 days after the last injection. Immediately after killing the animals, samples of the liver were taken and autoradiography was performed. RESULTS: After continuous labeling, more than 90% of the cells in the liver were labeled. Mean grain counts of hepatocytes decreased to half over approximately 100 days. Those of bile duct cells decreased at a slower rate (50%) than hepatocytes. Mean grain counts of hepatocytes decreased over the regions, although those in perivenular region decreased more rapidly in comparison to those in periportal region. CONCLUSIONS: The present study indicated that most cells in the liver arise postnatally. The changes in labeling of cells show that there is no special zone for proliferation of hepatocytes and they renew in all regions of the hepatic lobule, suggesting (i) that hepatocytes are supplied by postnatal replication and (ii) streaming of hepatocytes from periportal to pericentral regions does not occur in the adult mouse liver. The bile duct cells renewed more rapidly than hepatocytes.