title: Identification of proliferating human hepatic cells from human induced pluripotent stem cells.
abstract: Mass-scale production of hepatocytes from human induced pluripotent stem cells (iPSCs) with functional properties of primary hepatocytes is of great value in clinical transplantation for liver failure as well as in facilitating drug development by predicting humanized drug metabolism profiles. In this report, we generated human hepatocyte-like cells from human iPSCs with the use of a stepwise protocol. Aiming at future clinical and industrial application, it is important to determine the suitable stage of iPSC-derived hepatic cells that possess high proliferative capacity to intensively expand the hepatic cells. Ki67 immunostaining showed that human iPSC-derived hepatic endoderm cells contained Ki67(+) cells at the highest level in the middle stage of hepatic differentiation, suggesting that the abundance of proliferating hepatic progenitor cells exists in this stage. Extensive expansion and differentiation of human iPSC-derived hepatic progenitors will provide future perspectives in transplantation therapy and drug development.
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Advanced Medical Research Center, Yokohama City University, Yokohama, Japan; PRESTO, Japan Science and Technology Agency, Kawaguchi, Japan. Electronic address: ttakebe@yokohama-cu.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Takebe
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sekine
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Koike
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Advanced Medical Research Center, Yokohama City University, Yokohama, Japan. Electronic address: rtanigu@yokohama-cu.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Taniguchi
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology*; D019394:Ki-67 Antigen / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D015415:Biomarkers; D019394:Ki-67 Antigen