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Identification of adult rat hepatic progenitor cells that can reconstitute the liver
Author(s) -
Yovchev Mladen,
Grozdanov Petar,
Zhou Hongchao,
Guha Chandan,
Dabeva Mariana
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a70
Subject(s) - cd90 , cd34 , progenitor cell , pathology , transplantation , liver transplantation , chemistry , cd44 , microbiology and biotechnology , biology , stem cell , medicine , cell , biochemistry
In recent years there is extensive search for identification of intrahepatic and extrahepatic cells that can restore liver mass and function. Liver reconstitution by adult rat hepatic progenitor/oval cells (AHPC) has not been reported yet. In this work we identified the AHPC capable of reconstituting the injured liver. AHPC were activated in F344 rats: D‐galactosamine‐treated or 2‐AAF‐treated and subjected to partial hepatectomy. The recipient animals were DPP4 − , F344 normal or treated with retrorsine rats subjected to partial hepatectomy (Rs/PH). Liver repopulation by transplanted cells was evaluated by scanning the liver section after histochemical staining for DPP4. Transplantation of AHPC enriched fractions (2 x 10 7 , of which 40 % were CK‐19 + , a marker of oval cells), reconstituted completely in four weeks the liver of Rs/PH treated animals: megalocytes disappeared and the liver regained its normal lobular structure. Although not frequently, bile ducts composed of donor cells were also present. To identify precisely the AHPC that repopulate the injured liver we purified the oval cells using the surface antigen Ep‐CAM and magnetic beads. The Ep‐CAM + cells (65–95% purity) engrafted, proliferated and differentiated forming multiple clusters in the Rs/PH donor livers. RT/PCR and immunofluorescent analyses of the Ep‐CAM + cells confirmed our previous data (Yovchev et al ., Hepatology, in press). Thus, the AHPC capable of reconstituting the liver are epithelial cells expressing Ep‐CAM, AFP, CK‐19, GGT, DLK‐1, DPP4, CD44, CD34, CD133, vimentin but not CD90. Supported by NIH grant R01 DK59321