title: Perivascular mesenchymal progenitors in human fetal and adult liver.
abstract: The presence of mesenchymal stem cells (MSCs) has been described in various organs. Pericytes possess a multilineage differentiation potential and have been suggested to be one of the developmental sources for MSCs. In human liver, pericytes have not been defined. Here, we describe the identification, purification, and characterization of pericytes in human adult and fetal liver. Flow cytometry sorting revealed that human adult and fetal liver contains 0.56%±0.81% and 0.45%±0.39% of CD146(+)CD45(-)CD56(-)CD34(-) pericytes, respectively. Of these, 41% (adult) and 30% (fetal) were alkaline phosphatase-positive (ALP(+)). In situ, pericytes were localized around periportal blood vessels and were positive for NG2 and vimentin. Purified pericytes could be cultured extensively and had low population doubling times. Immunofluorescence of cultures demonstrated that cells were positive for pericyte and mesenchymal cell markers CD146, NG2, CD90, CD140b, and vimentin, and negative for endothelial, hematopoietic, stellate, muscle, or liver epithelial cell markers von Willebrand factor, CD31, CD34, CD45, CD144, CD326, CK19, albumin, α-fetoprotein, CYP3A7, glial fibrillary acid protein, MYF5, and Pax7 by gene expression; myogenin and alpha-smooth muscle actin expression were variable. Fluorescence-activated cell sorting analysis of cultures confirmed surface expression of CD146, CD73, CD90, CD10, CD13, CD44, CD105, and ALP and absence of human leukocyte antigen-DR. In vitro differentiation assays demonstrated that cells possessed robust osteogenic and myogenic, but low adipogenic and low chondrogenic differentiation potentials. In functional in vitro assays, cells had typical mesenchymal strong migratory and invasive activity. In conclusion, human adult and fetal livers harbor pericytes that are similar to those found in other organs and are distinct from hepatic stellate cells.
authors.affiliation: Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Gerlach
authors.forename: Patrick
authors.initials: P
authors.lastname: Over
authors.forename: Morris E
authors.initials: ME
authors.lastname: Turner
authors.forename: Robert L
authors.initials: RL
authors.lastname: Thompson
authors.forename: Hubert G
authors.initials: HG
authors.lastname: Foka
authors.forename: William C W
authors.initials: WC
authors.lastname: Chen
authors.forename: Bruno
authors.initials: B
authors.lastname: Péault
authors.forename: Bruno
authors.initials: B
authors.lastname: Gridelli
authors.forename: Eva
authors.initials: E
authors.lastname: Schmelzer
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000941:Antigens / Q000378:metabolism; D051929:CD146 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002469:Cell Separation; D005333:Fetus / Q000166:cytology*; D020869:Gene Expression Profiling; D055166:Hepatic Stellate Cells; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000196:embryology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D020286:Pericytes / Q000166:cytology*; D011509:Proteoglycans / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000469:Alkaline Phosphatase; D000941:Antigens; D051929:CD146 Antigen; D011509:Proteoglycans; D020797:Receptor, Platelet-Derived Growth Factor beta; D018800:Thy-1 Antigens; D014746:Vimentin; D000099216:Chondroitin Sulfate Proteoglycan 4