help button home button Am J Pathol JNCI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dabeva, M. D.
Right arrow Articles by Shafritz, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dabeva, M. D.
Right arrow Articles by Shafritz, D. A.
(American Journal of Pathology. 2000;156:2017-2031.)
© 2000 American Society for Investigative Pathology

Regular Articles

Proliferation and Differentiation of Fetal Liver Epithelial Progenitor Cells after Transplantation into Adult Rat Liver

Mariana D. Dabeva*{dagger}{ddagger}, Petko M. Petkov*{dagger}{ddagger}, Jaswinder Sandhu*{dagger}{ddagger}, Ran Oren||, Ezio Laconi**, Ethel Hurston*{dagger}{ddagger} and David A. Shafritz*{dagger}{ddagger}§¶

From the Marion Bessin Liver Research Center,*
the Division of Gastroenterology, Hepatology and Nutrition,{dagger}
and the Departments of Medicine,{ddagger}
Cell Biology,§
and Pathology,
Albert Einstein College of Medicine, Bronx, New York; the Department of Gastroenterology,||
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; and the Istituto di Patologia Sperimentale,**
Ospedale Oncologico "A Businco", University of Cagliari, Cagliari, Italy

To identify cells that have the ability to proliferate and differentiate into all epithelial components of the liver lobule, we isolated fetal liver epithelial cells (FLEC) from ED 14 Fischer (F) 344 rats and transplanted these cells in conjunction with two-thirds partial hepatectomy into the liver of normal and retrorsine (Rs) treated syngeneic dipeptidyl peptidase IV mutant (DPPIV-) F344 rats. Using dual label immunohistochemistry/in situ hybridization, three subpopulations of FLEC were identified: cells expressing both {alpha}-fetoprotein (AFP) and albumin, but not CK-19; cells expressing CK-19, but not AFP or albumin, and cells expressing AFP, albumin, and cytokeratins-19 (CK-19). Proliferation, differentiation, and expansion of transplanted FLEC differed significantly in the two models. In normal liver, 1 to 2 weeks after transplantation, mainly cells with a single phenotype, hepatocytic (expressing AFP and albumin) or bile ductular (expressing only CK-19), had proliferated. In Rs-treated rats, in which the proliferative capacity of endogenous hepatocytes is impaired, transplanted cells showed mainly a dual phenotype (expressing both AFP/albumin and CK-19). One month after transplantation, DPPIV+ FLEC engrafted into the parenchyma exhibited an hepatocytic phenotype and generated new hepatic cord structures. FLEC, localized in the vicinity of bile ducts, exhibited a biliary epithelial phenotype and formed new bile duct structures or were incorporated into pre-existing bile ducts. In the absence of a proliferative stimulus, ED 14 FLEC did not proliferate or differentiate. Our results demonstrate that 14-day fetal liver contains lineage committed (unipotential) and uncommitted (bipotential) progenitor cells exerting different repopulating capacities, which are affected by the proliferative status of the recipient liver and the host site within the liver where the transplanted cells become engrafted. These findings have important implications in future studies directed toward liver repopulation and ex vivo gene therapy.




This article has been cited by other articles:


Home page
 DevelopmentHome page
R. Simper-Ronan, K. Brilliant, D. Flanagan, M. Carreiro, H. Callanan, E. Sabo, and D. C. Hixson
Cholangiocyte marker-positive and -negative fetal liver cells differ significantly in their ability to regenerate the livers of adult rats exposed to retrorsine
Development, November 1, 2006; 133(21): 4269 - 4279.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
M. Oertel, A. Menthena, Y.-Q. Chen, and D. A. Shafritz
Properties of Cryopreserved Fetal Liver Stem/Progenitor Cells That Exhibit Long-Term Repopulation of the Normal Rat Liver
Stem Cells, October 1, 2006; 24(10): 2244 - 2251.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
M. H. Walkup and D. A. Gerber
Hepatic Stem Cells: In Search of
Stem Cells, August 1, 2006; 24(8): 1833 - 1840.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
A. Menthena, N. Deb, M. Oertel, P. N. Grozdanov, J. Sandhu, S. Shah, C. Guha, D. A. Shafritz, and M. D. Dabeva
Bone Marrow Progenitors Are Not the Source of Expanding Oval Cells in Injured Liver
Stem Cells, November 1, 2004; 22(6): 1049 - 1061.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Strick-Marchand, S. Morosan, P. Charneau, D. Kremsdorf, and M. C. Weiss
Bipotential mouse embryonic liver stem cell lines contribute to liver regeneration and differentiate as bile ducts and hepatocytes
PNAS, June 1, 2004; 101(22): 8360 - 8365.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
BASL abstracts
Gut, May 1, 2003; 52(5): e1 - 31.
[Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
T. Cantz, D. M. Zuckerman, M. R. Burda, M. Dandri, B. Goricke, S. Thalhammer, W. M. Heckl, M. P. Manns, J. Petersen, and M. Ott
Quantitative Gene Expression Analysis Reveals Transition of Fetal Liver Progenitor Cells to Mature Hepatocytes after Transplantation in uPA/RAG-2 Mice
Am. J. Pathol., January 1, 2003; 162(1): 37 - 45.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J.-E. Allain, I. Dagher, D. Mahieu-Caputo, N. Loux, M. Andreoletti, K. Westerman, P. Briand, D. Franco, P. Leboulch, and A. Weber
Immortalization of a primate bipotent epithelial liver stem cell
PNAS, March 19, 2002; 99(6): 3639 - 3644.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
R. SUSICK, N. MOSS, H. KUBOTA, E. LECLUYSE, G. HAMILTON, T. LUNTZ, J. LUDLOW, J. FAIR, D. GERBER, K. BERGSTRAND, et al.
Hepatic Progenitors and Strategies for Liver Cell Therapies
Ann. N.Y. Acad. Sci., November 1, 2001; 944(1): 398 - 419.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. S. Sandhu, P. M. Petkov, M. D. Dabeva, and D. A. Shafritz
Stem Cell Properties and Repopulation of the Rat Liver by Fetal Liver Epithelial Progenitor Cells
Am. J. Pathol., October 1, 2001; 159(4): 1323 - 1334.
[Abstract] [Full Text]

Home page
 Cell Growth Differ.Home page
M. L. Dumble, B. Knight, E. A. Quail, and G. C. T. Yeoh
Hepatoblast-like Cells Populate the Adult p53 Knockout Mouse Liver: Evidence for a Hyperproliferative Maturation-arrested Stem Cell Compartment
Cell Growth Differ., May 1, 2001; 12(5): 223 - 231.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
H. Zulewski, E. J. Abraham, M. J. Gerlach, P. B. Daniel, W. Moritz, B. Müller, M. Vallejo, M. K. Thomas, and J. F. Habener
Multipotential Nestin-Positive Stem Cells Isolated From Adult Pancreatic Islets Differentiate Ex Vivo Into Pancreatic Endocrine, Exocrine, and Hepatic Phenotypes
Diabetes, March 1, 2001; 50(3): 521 - 533.
[Abstract] [Full Text]

Home page
 J. Cell Biol.Home page
A. Suzuki, Y.-w. Zheng, S. Kaneko, M. Onodera, K. Fukao, H. Nakauchi, and H. Taniguchi
Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver
J. Cell Biol., January 7, 2002; 156(1): 173 - 184.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2000 by the American Society for Investigative Pathology.