Extrahepatic Cells Contribute to the Progenitor/Stem Cell Response Following Reduced-Size Liver Transplantation in Mice

Abstract

The extent to which extrahepatic cells participate in liver regeneration following transplantation is not known. Either full-size or reduced-size livers from wild-type mice were implanted into green fluorescent protein–positive (GFP⁺) transgenic recipient mice to determine whether regenerated liver contained host-derived GFP⁺ hepatic cells. After reduced-size liver transplantation, GFP⁺ cells were localized to the portal zone of the liver lobule. Interestingly, GFP⁺ cells stained for CD117, a marker for progenitor cells, beginning 2 days after transplantation. A significant number of GFP⁺ CD117⁺ cells were identified in donor livers after 28 days. GFP⁺ cells comprised nearly 9% of the donor liver 28 days after reduced-size liver transplant. Moreover, GFP⁺ cells also expressed the hepatic progenitor cell marker A6 and novel marker hepatic-specific antigen (HSA), as well as stem cell antigen-1 (Sca-1). Interestingly, some GFP⁻ cells also were stained for CD117 and A6, suggesting that both extrahepatic and intrahepatic stem cells were present and may have contributed to the regenerative response under these conditions. Reduced-size liver transplantation using GFP⁺ transgenic mice supports the hypothesis that recipient-derived progenitor cells are present and may contribute to liver regeneration following transplantation.