title: Adult-derived human liver mesenchymal-like cells as a potential progenitor reservoir of hepatocytes?
abstract: It is currently accepted that adult tissues may develop and maintain their own stem cell pools. Because of their higher safety profile, adult stem cells may represent an ideal candidate cell source to be used for liver cell therapies. We therefore evaluated the differentiation potential of mesenchymal-like cells isolated from adult human livers. Mesenchymal-like cells were isolated from enzymatically digested adult human liver and expanded in vitro. Cell characterization was performed using flow cytometry, RT-PCR, and immunofluorescence, whereas the differentiation potential was evaluated both in vitro after incubation with specific media and in vivo after intrasplenic transplantation of uPA(+/+)-SCID and SCID mice. Adult-derived human liver mesenchymal-like cells expressed both hepatic and mesenchymal markers among which albumin, CYP3A4, vimentin, and alpha-smooth muscle actin. In vitro differentiation studies demonstrated that these mesenchymal-like cells are preferentially determined to differentiate into hepatocyte-like cells. Ten weeks following intrasplenic transplantation into uPA(+/+)-SCID mice, recipient livers showed the presence of human hepatocytic cell nodules positive for human albumin, prealbumin, and alpha-fetoprotein. In SCID transplanted liver mice, human hepatocyte-like cells were mostly found near vascular structures 56 days posttransplantation. In conclusion, the ability of isolated adult-derived liver mesenchymal stem-like cells to proliferate and differentiate into hepatocyte-like cells both in vitro and in vivo leads to propose them as an attractive expandable cell source for stem cell therapy in human liver diseases.
authors.affiliation: Université catholique de Louvain, Laboratory of Pediatric Hepatology & Cell Therapy, B-1200 Brussels, Belgium. mustapha.najimi@pedi.ucl.ac.be
authors.forename: Mustapha
authors.initials: M
authors.lastname: Najimi
authors.forename: Dung Ngoc
authors.initials: DN
authors.lastname: Khuu
authors.forename: Philippe Antoine
authors.initials: PA
authors.lastname: Lysy
authors.forename: Nawal
authors.initials: N
authors.lastname: Jazouli
authors.forename: Jorge
authors.initials: J
authors.lastname: Abarca
authors.forename: Christine
authors.initials: C
authors.lastname: Sempoux
authors.forename: Etienne Marc
authors.initials: EM
authors.lastname: Sokal
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D048430:Cell Shape; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous
chemical_list: D015415:Biomarkers