title: Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells.
abstract: We have derived from normal human, mouse, and rat postnatal bone marrow primitive, multipotent adult progenitor cells (MAPCs) that can differentiate into most mesodermal cells and neuroectodermal cells in vitro and into all embryonic lineages in vivo. Here, we show that MAPCs can also differentiate into hepatocyte-like cells in vitro. Human, mouse, and rat MAPCs, cultured on Matrigel with FGF-4 and HGF, differentiated into epithelioid cells that expressed hepatocyte nuclear factor-3beta (HNF-3beta), GATA4, cytokeratin 19 (CK19), transthyretin, and alpha-fetoprotein by day 7, and expressed CK18, HNF-4, and HNF-1alpha on days 14-28. Virtually all human, as well as a majority of rodent cells stained positive for albumin and CK18 on day 21; 5% (rodent) to 25% (human) cells were binucleated by day 21. These cells also acquired functional characteristics of hepatocytes: they secreted urea and albumin, had phenobarbital-inducible cytochrome p450, could take up LDL, and stored glycogen. MAPCs, which can be expanded in vitro and maintained in an undifferentiated state for more than 100 population doublings, can thus differentiate into cells with morphological, phenotypic, and functional characteristics of hepatocytes. MAPCs may therefore be an ideal cell for in vivo therapies for liver disorders or for use in bioartificial liver devices.
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis 55455, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schwartz
authors.forename: Morayma
authors.initials: M
authors.lastname: Reyes
authors.forename: Lisa
authors.initials: L
authors.lastname: Koodie
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Jiang
authors.forename: Mark
authors.initials: M
authors.lastname: Blackstad
authors.forename: Troy
authors.initials: T
authors.lastname: Lund
authors.forename: Todd
authors.initials: T
authors.lastname: Lenvik
authors.forename: Sandra
authors.initials: S
authors.lastname: Johnson
authors.forename: Wei-Shou
authors.initials: WS
authors.lastname: Hu
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D051381:Rats
chemical_list: D015415:Biomarkers