title: CD133+ hepatic stellate cells are progenitor cells.
abstract: Hepatic stellate cells (HSC) play an important role in the development of liver fibrosis. Here, we report that HSC express the stem/progenitor cell marker CD133 and exhibit properties of progenitor cells. CD133+ HSC of rats were selected by specific antibodies and magnetic cell sorting. Selected cells displayed typical markers of HSC, endothelial progenitor cells (EPC), and monocytes. In cell culture, CD133+ HSC transformed into alpha-smooth muscle actin positive myofibroblast-like cells, whereas application of cytokines known to facilitate EPC differentiation into endothelial cells led to the formation of branched tube-like structures and induced expression of the endothelial cell markers endothelial nitric oxide synthase and vascular-endothelial cadherin. Moreover, cytokines that guide stem cells to develop hepatocytes led to the appearance of rotund cells and expression of the hepatocyte markers alpha-fetoprotein and albumin. It is concluded that CD133+ HSC are a not yet recognized progenitor cell compartment with characteristics of early EPC. Their potential to differentiate into endothelial or hepatocyte lineages suggests important functions of CD133+ HSC during liver regeneration.
authors.affiliation: Clinic of Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany. Claus.Kordes@t-online.de
authors.forename: Claus
authors.initials: C
authors.lastname: Kordes
authors.forename: Iris
authors.initials: I
authors.lastname: Sawitza
authors.forename: Alexis
authors.initials: A
authors.lastname: Müller-Marbach
authors.forename: Niloofar
authors.initials: N
authors.lastname: Ale-Agha
authors.forename: Verena
authors.initials: V
authors.lastname: Keitel
authors.forename: Hanne
authors.initials: H
authors.lastname: Klonowski-Stumpe
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D006023:Glycoproteins / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; C000606025:Prom1 protein, rat