title: Successful isolation of liver progenitor cells by aldehyde dehydrogenase activity in naïve mice.
abstract: The role of progenitor cells in liver repair and fibrosis has been extensively described, but their purification remains a challenge, hampering their characterization and use in regenerative medicine. To address this issue, we developed an easy and reproducible liver progenitor cell (LPC) isolation strategy based on aldehyde dehydrogenase (ALDH) activity, a common feature shared by many progenitor cells. We demonstrate that a subset of nonparenchymal mouse liver cells displays high levels of ALDH activity, allowing the isolation of these cells by fluorescence-activated cell sorting. Immunocytochemistry and qPCR analyses on freshly isolated ALDH(+) cells reveal an enrichment in cells expressing liver stem cell markers such as EpCAM, CK19, CD133, and Sox9. In culture, the ALDH(+) population can give rise to functional hepatocyte-like cells as illustrated by albumin and urea secretion and cytochrome P450 activity. ALDH1A1 expression can be detected in canals of Hering and bile duct epithelial cells and is increased on liver injury. Finally, we showed that the isolation and differentiation toward hepatocyte-like cells of LPCs with high ALDH activity is also successfully applicable to human liver samples.
  
  
  CONCLUSIONS
  High ALDH activity is a feature of LPCs that can be taken advantage of to isolate these cells from untreated mouse as well as human liver tissues. This novel protocol is practically relevant, because it provides an easy and nontoxic method to isolate liver stem cells from normal tissue for potential therapeutic purposes.
authors.affiliation: Liver Cell Biology Laboratory, Vrije Universiteit Brussels, Brussels, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Dollé
authors.forename: Jan
authors.initials: J
authors.lastname: Best
authors.forename: Christophe
authors.initials: C
authors.lastname: Empsen
authors.forename: Jie
authors.initials: J
authors.lastname: Mei
authors.forename: Elke
authors.initials: E
authors.lastname: Van Rossen
authors.forename: Philip
authors.initials: P
authors.lastname: Roelandt
authors.forename: Sarah
authors.initials: S
authors.lastname: Snykers
authors.forename: Mustapha
authors.initials: M
authors.lastname: Najimi
authors.forename: Feras
authors.initials: F
authors.lastname: Al Battah
authors.forename: Neil D
authors.initials: ND
authors.lastname: Theise
authors.forename: Konrad
authors.initials: K
authors.lastname: Streetz
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
authors.forename: Isabelle A
authors.initials: IA
authors.lastname: Leclercq
authors.forename: Catherine
authors.initials: C
authors.lastname: Verfaillie
authors.forename: Vera
authors.initials: V
authors.lastname: Rogiers
authors.forename: Albert
authors.initials: A
authors.lastname: Geerts
authors.forename: Leo A
authors.initials: LA
authors.lastname: van Grunsven
mesh_terms: D000071916:AC133 Antigen; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D053539:Keratin-19 / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D051379:Mice; D010455:Peptides / Q000378:metabolism; D050697:Retinal Dehydrogenase; D055758:SOX9 Transcription Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; D053539:Keratin-19; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase