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ORIGINAL RESEARCH ARTICLE

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

Lars O. Conzelmann^*, Ian N. Hines^*,1, Michael Kremer^*, Ashley W. Perry^*, John J. Lemasters^*, and Michael D. Wheeler^*,,

^* Center for Alcohol Studies, Department of Cell Biology and Anatomy, Department of Nutrition, and Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599

To whom requests for reprints should be addressed at ¹ Laboratory of Hepatobiology and Toxicology, Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail: ihines{at}med.unc.edu

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.

Key Words: GFP⁺ transgenic mice • regeneration • CD117 • biliary epithelia • -fetoprotein • Sca-1

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