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Springerplus. 2013 Sep 8;2:446. doi: 10.1186/2193-1801-2-446. eCollection 2013.

Contribution of extrahepatic small cells resembling small hepatocyte-like progenitor cells to liver mass maintenance in transplantation model of retrorsine-pretreated liver.

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  • 1Department of Surgery, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research 771, Baltimore, MD 21205 USA ; Department of Surgery and Cancer Treatment Center, Kochi Medical School, Kohasu Oko-cho, Nankoku-city, Kochi, 783-8505 Japan.



Retrorsine selectively inhibits hepatocyte proliferation and following liver injury evokes small hepatocyte-like progenitor cells. The aim of this study is to find out whether endogenous extrahepatic cells contribute to small hepatocyte-like progenitor cells after retrorsine treatment.


Wild-type Lewis rat liver exposed to retrorsine was transplanted into GFP transgenic Lewis rat. GFP positive, albumin-producing polygonal cells were expected as reciepient-derived hepatocyte-like cells.


Four weeks after transplantation of 50% volume of retrorsine-pretreated liver, the rate of GFP positive hepatocyte-like cells was 0.02365%. Majority of these cells resided as single cells and their cell size was significantly larger than that of normal hepatocytes (mean cell size; 799.4 um(2) vs. 451.3 um(2), p<0.0001). At eight weeks, clusters of GFP positive small-size albumin-producing cells appeared and occupied 0.00759% of hepatocytes. The morphology of these cells was similar to that of small hepatocyte-like progenitor cells, 12.5% of them were Ki67 positive, majority of them were negative for CYP1A2 staining, and some clusters contained larger cells indicating further maturation.


Endogenous extrahepatic cells can form a cluster of small cells resembling small hepatocyte-like progenitor cells in a transplanted retrorsine-pretreated liver. The contribution of extrahepatic cells to liver mass maintenance is quite low and its importance is unclear.


GFP; Liver transplantation; Retrorsine; SHPC

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