Thrombopoietin is a growth factor for rat hepatic progenitors.
OBJECTIVE
The liver is the primary site of hematopoiesis during fetal development; it has been shown that thrombopoietin (TPO) produced by the liver during fetal development is a major regulator of megakaryocytopoiesis. As maximum liver growth and hematopoiesis occur simultaneously, we hypothesized that TPO may act as a growth factor for hepatic progenitors. Therefore, the influence of TPO on the proliferation of fetal hepatic progenitors in vitro compared with that of adult hepatocytes was analyzed. The expression of the TPO receptor, c-mpl, was investigated in fetal and adult liver.


METHODS
Cell proliferation was measured by bromodeoxyuridine incorporation and total cell counts. TPO and c-mpl gene expression was investigated by reverse transcription polymerase chain reaction. The cell surface expression of c-mpl was analyzed in fetal and adult human liver by immunohistochemistry.


RESULTS
Hepatic progenitors of fetal and adult liver but not hepatocytes expressed the TPO receptor, c-mpl, on the cell surface. Fetal hepatic progenitors expressed mRNA for TPO and its receptor. TPO stimulated cell proliferation and increased cell numbers of cultured rat fetal hepatic progenitors but not adult hepatocytes.


CONCLUSIONS
We conclude that TPO acts in addition to its known role in megakaryocytopoiesis as a growth factor for hepatic progenitors but not hepatocytes in vitro; thus, TPO represents a growth factor for hepatic progenitors during fetal liver development.
Schmelzer
Eva
E
Department of Cell Culture and Stem Cell Biology, Biomedical Biotechnical Center, University of Leipzig, Leipzig, Germany. eva.schmelzer@bbz.uni-leipzig.de
Deiwick
Andrea
A
Bruns
Helge
H
Fiegel
Henning C
HC
Bader
Augustinus
A
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D053686:Fetal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D006133:Growth Substances / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000196:embryology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013926:Thrombopoietin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D006133:Growth Substances; D012333:RNA, Messenger; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin