Extrahepatic cells contribute to the progenitor/stem cell response following reduced-size liver transplantation in mice.
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.
Conzelmann
Lars O
LO
Laboratory of Hepatobiology and Toxicology, Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Hines
Ian N
IN
Kremer
Michael
M
Perry
Ashley W
AW
Lemasters
John J
JJ
Wheeler
Michael D
MD
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D008115:Liver Regeneration; D016031:Liver Transplantation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D018183:Transplantation Chimera / Q000378:metabolism
D000943:Antigens, Differentiation