Cytochrome P450 mRNA expressions along with in vitro differentiation of hepatocyte precursor cells from fetal, young and old rats.
Non-differentiated cells are attractive targets for cell therapy. During liver regeneration oval cells intensively proliferate and differentiate extending their metabolic activity. Hepatic cytochromes P450 (CYPs) can be linked either with metabolic activation of toxic compounds or drug metabolism. We investigated the differentiation and biotransformative potential of non-differentiated cells in primary cell cultures isolated from livers of fetuses (16-days-old), young (4-months-old) and old (20-months-old) rats. Under the conditions of experimental hepatocarcinogenesis, adult rats were fed for three weeks with CDE diet. Liver cells were cultured and precursor cells were differentiated to hepatocytes following induction with sodium butyrate (SB) or dimethyl sulphoxide (DMSO) in culture on MesenCult medium. We identified a number of cells expressing Thy-1, CD34, alpha-fetoprotein, cytokeratines--CK18 or CK19 and glutathione transferases--GSTpi or GSTalpha. In vitro differentiation of these cells, isolated from CDE-treated rats begun earlier as compared to non-treated ones. Age-dependent changes in the cell differentiation sequence, as well as CYPmRNA expression sequence accompanying precursor cells differentiation, were also observed. mRNA expression of CYP1A2, CYP2B1/2 and CYP3A1 was higher in the cells of young rats, but in the case of CYP2E1--in the cells of old rats. It was concluded that both proliferation and differentiation potential of oval cells, decreased with age.
Czekaj
Piotr
P
Department of Histology, Medical University of Silesia, Katowice, Poland. pcz@sum.edu.pl
Bryzek
Aleksandra
A
Czekaj
Tomasz M
TM
Koryciak-Komarska
Halina
H
Wiaderkiewicz
Anna
A
Plewka
Danuta
D
Sieroń
Aleksander L
AL
D000375:Aging / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D005333:Fetus / Q000166:cytology / Q000201:enzymology*; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000166:cytology* / Q000201:enzymology; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology*; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D003577:Cytochrome P-450 Enzyme System