Expansion of transplanted hepatocytes during liver regeneration

Background. Successful clinical application of hepatocyte transplantation has been limited by poor engraftment of the recipient liver by transplanted hepatocytes. Methods. To address the hypothesis that liver regeneration induced by an acute hepatotoxic injury promotes expansion of transplanted hepatocytes, we injected β-galactosidase-labeled hepatocytes intrasplenically into mice 24 hr after treatment with carbon tetrachloride (CCl₄) and into untreated controls. Results. Macroscopic examination of whole liver segments identified clusters of transplanted hepatocytes uniformly spread on the capsular surface of the recipient liver and in the liver core following the distribution pattern of portal vein branches. Frozen sections showed that although the degree of initial engraftment of transplanted hepatocytes was similar in CCl₄ treated and control livers, there was a fourfold increase of engrafted hepatocytes in CCl₄-treated livers 10 days after transplantation which persisted to 28 days. Conclusions. We conclude that the number of transplanted hepatocytes increases in response to regeneration signal triggered by an acute hepatocyte-specific liver injury.