title: Steatotic liver: a suitable source for the isolation of hepatic progenitor cells.
abstract: BACKGROUND
  Alternative and/or complementary sources of cells such as hepatic progenitor cells (HPC) are under investigation for hepatic cell therapy purposes. Steatotic livers are those most commonly rejected for clinical transplantation and are also unsuitable for good quality hepatocyte isolation.
  
  
  OBJECTIVE
  Taken together these two facts, our aim was to investigate whether they could represent a suitable source for the isolation of progenitor cells.
  
  
  METHODS
  Rats fed for 7 weeks with methionine-choline deficient diets showing proved steatotic signs (i.e. increase in hepatic lipids; macrovesicular steatosis) and steatotic and normal human liver samples were used to study the expression of HPC markers and to isolate these cells.
  
  
  RESULTS
  In the liver of the steatotic rats there was a significant increase in HPC (known as oval cells in rodents) markers such as Thy-1, epithelial cell adhesion molecule (EpCAM) and OV-6 (2-, 3- and 5-fold increase respectively). Additionally, there was an increase in the yield of isolated oval cells compared to control rats. Similarly, studies using human livers clearly confirmed an increase in the expression of HPC markers in the steatotic tissue and a significant rise in the number of isolated progenitor cells (EpCAM+, Thy-1+, OV-6+) (10, 12 and 11.6 × 10(4)  cells/g of tissue respectively).
  
  
  CONCLUSIONS
  These data suggest that steatotic livers, discarded for orthotopic liver transplantation and hepatocyte isolation, could be a suitable source for large scale isolation of HPC which might be potential candidates in liver cell therapy.
authors.affiliation: Unidad de Hepatología Experimental, Centro de Investigación, Hospital La Fe, Valencia, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Tolosa
authors.forename: Ana
authors.initials: A
authors.lastname: Bonora-Centelles
authors.forename: M
authors.initials: M
authors.lastname: Teresa Donato
authors.forename: Eugenia
authors.initials: E
authors.lastname: Pareja
authors.forename: Alejandro
authors.initials: A
authors.lastname: Negro
authors.forename: Silvia
authors.initials: S
authors.lastname: López
authors.forename: José V
authors.initials: JV
authors.lastname: Castell
authors.forename: M
authors.initials: M
authors.lastname: José Gómez-Lechón
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D002796:Choline Deficiency / Q000150:complications; D004195:Disease Models, Animal; D000071858:Epithelial Cell Adhesion Molecule; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008715:Methionine / Q000172:deficiency; D051381:Rats; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D018800:Thy-1 Antigens / Q000378:metabolism; D013997:Time Factors
chemical_list: D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D015415:Biomarkers; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D018800:Thy-1 Antigens; C115011:oval cell marker OV-6; D008715:Methionine