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

Hiromichi Maeda, Yoshihiro Ota, Yongchung Wang, Kalyani Ramachandran, Robert A. Montgomery, George Melville Williams, Zhaoli Sun

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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. Methods: 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. Results: 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 um2 vs. 451.3 um2, 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. Conclusion: 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.

Original languageEnglish (US)
Article number446
Pages (from-to)1-11
Number of pages11
JournalSpringerPlus
Volume2
Issue number1
DOIs
StatePublished - 2013

Keywords

  • GFP
  • Liver transplantation
  • Retrorsine
  • SHPC

ASJC Scopus subject areas

  • General

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