Genomic and functional characterization of stellate cells isolated from human cirrhotic livers.
OBJECTIVE
Hepatic stellate cells (HSCs) are believed to participate in liver fibrogenesis and portal hypertension. Knowledge on human HSCs is based on studies using HSCs isolated from normal livers. We investigated the phenotypic, genomic and functional characteristics of HSCs from human cirrhotic livers.


METHODS
HSC were obtained from normal and cirrhotic human livers. Cells were characterized by immunocytochemistry and gene microarray analysis. Cell proliferation, Ca(2+) changes and cell contraction were assessed by 3H-thymidine incorporation and by using an epifluorescence microscope.


RESULTS
HSCs freshly isolated from human cirrhotic livers showed phenotypical features of myofibroblasts. These features were absent in HSCs freshly isolated from normal human livers and become prominent after prolonged culture. HSCs from cirrhotic human livers markedly express genes involved in fibrogensis, inflammation and apoptosis. HSCs from normal livers after prolonged culture preferntially expressed genes related to fibrogenesis and contractility. Agonists induced proliferation, Ca(2+) increase and cell contraction in HSCs isolated from human cirrhotic livers. Response to agonists was more marked in culture-activated HSCs and was not observed in HSCs freshly isolated from normal livers.


CONCLUSIONS
HSCs from human cirrhotic livers show fibrogenic and contractile features. However, the current model of HSCs activated in culture does not exactly reproduce the activated phenotype found in cirrhotic human livers.
Sancho-Bru
Pau
P
Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalonia, Spain.
Bataller
Ramón
R
Gasull
Xavier
X
Colmenero
Jordi
J
Khurdayan
Valeriya
V
Gual
Arcadi
A
Nicolás
Josep M
JM
Arroyo
Vicente
V
Ginès
Pere
P
D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000235:genetics*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000502:physiology*; D016678:Genome; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*
D012313:RNA; D004247:DNA; D002118:Calcium