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Comparison of hepatic properties and transplantation of Thy‐1 + and Thy‐1 − cells isolated from embryonic day 14 rat fetal liver
Author(s) -
Oertel Michael,
Menthena Anuradha,
Chen YuanQing,
Shafritz David A.
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21775
Subject(s) - progenitor cell , embryonic stem cell , biology , fetus , liver cytology , transplantation , stem cell , haematopoiesis , stromal cell , andrology , microbiology and biotechnology , pathology , medicine , endocrinology , cancer research , pregnancy , biochemistry , genetics , liver metabolism , gene
Thy‐1, a marker of hematopoietic progenitor cells, is also expressed in activated oval cells of rat liver. Thy‐1 + cells are also in rat fetal liver and exhibit properties of bipotent hepatic epithelial progenitor cells in culture. However, no information is available concerning liver repopulation by Thy‐1 + fetal liver cells. Therefore, we isolated Thy‐1 + and Thy‐1 − cells from embryonic day (ED) 14 fetal liver and compared their gene expression characteristics in vitro and proliferative and differentiation potential after transplantation into adult rat liver. Fetal liver cells selected for Thy‐1 expression using immunomagnetic microbeads were enriched from 5.2%‐87.2% Thy‐1 + . The vast majority of alpha fetoprotein + , albumin + , cytokine‐19 + , and E‐cadherin + cells were found in cultured Thy‐1 − cells, whereas nearly all CD45 + cells were in the Thy‐1 + fraction. In normal rat liver, transplanted Thy‐1 + cells produced only rare, small DPPIV + cell clusters, very few of which exhibited a hepatocytic phenotype. In retrorsine‐treated liver, transplanted Thy‐1 + fetal liver cells achieved a 4.6%‐23.5% repopulation. In contrast, Thy‐1 − fetal liver cells substantially repopulated normal adult liver and totally repopulated retrorsine‐treated liver. Regarding the stromal cell–derived factor (SDF)–1/chemokine (C‐X‐C motif) receptor 4 (CXCR4) axis for stem cell homing, Thy‐1 + and Thy‐1 − fetal hepatic epithelial cells equally expressed CXCR4. However, SDF‐1α expression was augmented in bile ducts and oval cells in retrorsine/partial hepatectomy–treated liver, and this correlated with liver repopulation by Thy‐1 + cells. Conclusion: Highly enriched Thy‐1 + ED14 fetal liver cells proliferate and repopulate the liver only after extensive liver injury and represent a fetal hepatic progenitor cell population distinct from Thy‐1 − stem/progenitor cells, which repopulate the normal adult liver. (H EPATOLOGY 2007.)