Oval cell proliferation in cirrhosis in rats. An experimental study.
OBJECTIVE
Oval cells are liver stem cells involved in liver regeneration following liver damage. Previous studies have shown that pretreatment with a hepatocyte inhibitor is required to allow full oval cell activation. This study investigates whether oval cells develop and proliferate in a model of experimental liver fibrosis without pretreatment with a known hepatocyte inhibitor.


METHODS
The study comprised 66 male Wistar rats divided into two groups: A (n = 6): controls; and B (n = 60): CCl(4) injection (intraperitoneally 2 mL/kg bodyweight 1:1 volume in corn oil twice weekly). Rats were sacrificed at four, eight and 12 weeks. Liver tissues were evaluated for the degree of fibrosis (Masson's trichrome), cell proliferation (Ki67 antigen), expression of alpha-fetoprotein (AFP) mRNA (RT-PCR and in situ hybridization), AFP protein (Western blot) and cytokeratin-19. Cells with morphologic features of oval cells that were cytokeratin 19 (CK19)+ and AFP mRNA+ were scored in morphometric analysis.


RESULTS
Oval cells were present in all 66 specimens; their percentage was higher in group B compared to group A (P < 0.001). AFP mRNA and protein expression increased as fibrosis advanced. Similarly, the numbers of CK19+, AFP mRNA+ and Ki67+ oval cells were higher in advanced fibrosis stages.


CONCLUSIONS
This study demonstrates that oval cells develop and proliferate in a model of experimental liver fibrosis without pretreatment with a known hepatocytic inhibitor. However, further research is warranted in order to identify the exact molecular mechanisms involved in this process.
Tsamandas
Athanassios C
AC
Department of Pathology, University of Patras, School of Medicine, Patras, Greece.
Antonacopoulou
Anna
A
Kalogeropoulou
Christine
C
Tsota
Irene
I
Zabakis
Peter
P
Giannopoulou
Efstathia
E
Liava
Anna
A
Tzelepi
Vassiliki
V
Tepetes
Konstantinos
K
Petsas
Theodore
T
Kardamakis
Dimitrios
D
Kalofonos
Haralabos P
HP