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Hematopoietic mobilization in mice increases the presence of bone marrow–derived hepatocytes via in vivo cell fusion
Author(s) -
QuintanaBustamante Oscar,
AlvarezBarrientos Alberto,
Kofman Alexander V.,
Fabregat Isabel,
Bueren Juan A.,
Theise Neil D.,
Segovia José C.
Publication year - 2006
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.21005
Subject(s) - haematopoiesis , bone marrow , in vivo , biology , pathology , stem cell , immunology , medicine , microbiology and biotechnology
Abstract The mechanisms for in vivo production of bone marrow–derived hepatocytes (BMDHs) remain largely unclear. We investigated whether granulocyte colony–stimulating factor (G‐CSF)–mediated mobilization of hematopoietic cells increases the phenomenon. Recurrent liver injury in mice expressing green fluorescent protein (EGFP) in all hematopoietic‐derived cells was produced by 3 months of carbon tetrachloride (CCL 4 ) injections. Histologically, there were necrotic foci with histiocyte‐rich infiltrates, but little oval cell proliferation. Subsequently, some animals were mobilized with G‐CSF for 1, 2, or 3 weeks. Animals were sacrificed 1 month after growth factor treatment. BMDH percentages were lower than previously reported, though G‐CSF mobilization significantly augmented BMDH production in injured livers. BMDHs originating from in vivo fusion were evaluated by transplanting female EGFP + cells into male mice. Binucleated, EGFP + hepatocytes with one Y chromosome, indicating fusion, were identified. In conclusion , (1) mobilization of hematopoietic cells increases BMDH production and (2) as with the FAH‐null model, the first model demonstrating hematopoietic/hepatocyte fusion, recurring CCl 4 ‐induced injury has macrophage‐rich infiltrates, a blunted oval cell response, and a predominantly in vivo fusion process for circulating cell engraftment into the liver. These findings open the possibility of using hematopoietic growth factors to treat nonhematopoietic degenerative diseases. (H EPATOLOGY 2006;43:108–116.)