SERIAL TRANSPLANTATION REVEALS THE STEM-CELL-LIKE REGENERATIVE POTENTIAL OF ADULT-MOUSE HEPATOCYTES

Previous work has shown that adult mouse hepatocytes can divide at lea st 18 times in vivo. To test whether this represents the upper limit o f their regenerative capacity, we performed serial transplantation of hepatocytes in the fumarylacetoacetate hydrolase deficiency murine mod el of liver repopulation. Hepatocytes from adult donors were serially transplanted in Limiting numbers six times and resulted in complete re population during each cycle. This corresponds to a minimal number of 69 cell doublings or a 7.3 x 10(20)-fold expansion. No evidence for ab normal liver function or altered hepatic architecture was found in rep opulated animals. We conclude that a fraction of adult mouse hepatocyt es have growth potential similar to that of hematopoietic stem cells.