title: Isolation and characterization of portal branch ligation-stimulated Hmga2-positive bipotent hepatic progenitor cells.
abstract: Hepatic stem/progenitor cells are one of several cell sources that show promise for restoration of liver mass and function. Although hepatic progenitor cells (HPCs), including oval cells, are induced by administration of certain hepatotoxins in experimental animals, such a strategy would be inappropriate in a clinical setting. Here, we investigated the possibility of isolating HPCs in a portal branch-ligated liver model without administration of any chemical agents. A non-parenchymal cell fraction was prepared from the portal branch-ligated or non-ligated lobe, and seeded onto plates coated with laminin. Most of the cells died, but a small number were able to proliferate. These proliferating cells were cloned as portal branch ligation-stimulated hepatic cells (PBLHCs) by the limiting dilution method. The PBLHCs expressed cytokeratin19, albumin, and Hmga2. The PBLHCs exhibited metabolic functions such as detoxification of ammonium ions and synthesis of urea on Matrigel-coated plates in the presence of oncostatin M. In Matrigel mixed with type I collagen, the PBLHCs became rearranged into cystic and tubular structures. Immunohistochemical staining demonstrated the presence of Hmga2-positive cells around the interlobular bile ducts in the portal branch-ligated liver lobes. In conclusion, successful isolation of bipotent hepatic progenitor cell clones, PBLHCs, from the portal branch-ligated liver lobes of mice provides the possibility of future clinical application of portal vein ligation to induce hepatic progenitor cells.
authors.affiliation: Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakai
authors.forename: Yoh-ichi
authors.initials: Y
authors.lastname: Tagawa
authors.forename: Miho
authors.initials: M
authors.lastname: Tamai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Motoyama
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ogawa
authors.forename: Junpei
authors.initials: J
authors.lastname: Soeda
authors.forename: Takenari
authors.initials: T
authors.lastname: Nakata
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyagawa
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000254:growth & development; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D025743:HMGA2 Protein / Q000032:analysis / Q000096:biosynthesis; D022781:Hepatocytes / Q000166:cytology*; D008115:Liver Regeneration; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*
chemical_list: D025743:HMGA2 Protein