Hepatocyte transplantation has been successful in a number of animal models, raising hopes that their use could overcome the shortage of donor livers and surgical issues, but the procedure has not been as successful in patients. Scientists at the Martin Luther University Hale-Wittenberg, Germany, may have determined why. Although donor age is not a factor, it seems that recipient age may make the difference. The German study found that older rats had a repopulation rate of only 2%, 10 times less than that observed in younger ones. Furthermore, the transplanted cells worked equally well in the old and young animals, as measured by glycogen storage, but the younger animals had significantly higher levels of insulin-like growth factor (IGF)-1 needed for proliferation. The new study is the first to offer a possible mechanism for the failure of transplanted hepatocytes to proliferate in many human patients, and the first to suggest a way to compensate for the problem, said Dr Peggy Stock, a postdoctoral fellow in the laboratory of Dr Bruno Christ. She reported the study April 19 at Experimental Biology 2009 in New Orleans. The presentation was part of the scientific program of the American Society for Investigative Pathology. The researchers isolated hepatocytes from both 4-week-old rats and animals >35 weeks old. These healthy liver cells were then implanted into the livers of young animals (10 weeks, the equivalent of young adulthood) and “senescent” rats (>35 weeks). After 6 weeks, the amount of hepatocyte proliferation was determined by an assay of CD26 enzyme activity. The recipient animals were CD26 knockouts, giving the researchers a way to determine which and how many hepatocytes were part of the recipient liver and which had the CD26 gene product, indicating they originated from the transplant. Repopulation of hepatocytes was 20% in young rats, whether the cells came from a young or old donor. In older rats, by contrast, repopulation was only 2%. All the transplanted and proliferated cells were functional, whether they were transplanted into old or young rats and whether they came from old or young rats. However, IGF-1 was significantly higher in the juvenile rats. The next step, say the researchers, is to inject IGF-1 in old rats and see if this pretreatment increases the proliferation levels of hepatocyte cells.