PMID- 28757162 OWN - NLM STAT- MEDLINE DCOM- 20180423 LR - 20181113 IS - 2213-6711 (Electronic) IS - 2213-6711 (Linking) VI - 9 IP - 2 DP - 2017 Aug 8 TI - An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells. PG - 490-498 LID - S2213-6711(17)30273-4 [pii] LID - 10.1016/j.stemcr.2017.06.010 [doi] AB - During liver development, hepatoblasts and liver non-parenchymal cells (NPCs) such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) constitute the liver bud where they proliferate and differentiate. Accordingly, we reasoned that liver NPCs would support the maturation of hepatocytes derived from human induced pluripotent stem cells (hiPSCs), which usually exhibit limited functions. We found that the transforming growth factor beta and Rho signaling pathways, respectively, regulated the proliferation and maturation of LSEC and HSC progenitors isolated from mouse fetal livers. Based on these results, we have established culture systems to generate LSECs and HSCs from hiPSCs. These hiPSC-derived NPCs exhibited distinctive phenotypes and promoted self-renewal of hiPSC-derived liver progenitor cells (LPCs) over the long term in the two-dimensional culture system without exogenous cytokines and hepatic maturation of hiPSC-derived LPCs. Thus, a functional human liver model can be constructed in vitro from the LPCs, LSECs, and HSCs derived from hiPSCs. CI - Copyright (c) 2017 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Koui, Yuta AU - Koui Y AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. FAU - Kido, Taketomo AU - Kido T AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. Electronic address: kido@iam.u-tokyo.ac.jp. FAU - Ito, Toshimasa AU - Ito T AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. FAU - Oyama, Hiroki AU - Oyama H AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. FAU - Chen, Shin-Wei AU - Chen SW AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. FAU - Katou, Yuki AU - Katou Y AD - Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. FAU - Shirahige, Katsuhiko AU - Shirahige K AD - Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. FAU - Miyajima, Atsushi AU - Miyajima A AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. Electronic address: miyajima@iam.u-tokyo.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170727 PL - United States TA - Stem Cell Reports JT - Stem cell reports JID - 101611300 RN - 0 (Activated-Leukocyte Cell Adhesion Molecule) RN - 0 (Biomarkers) SB - IM MH - Activated-Leukocyte Cell Adhesion Molecule/metabolism MH - Animals MH - Biomarkers MH - *Cell Differentiation/genetics MH - Cells, Cultured MH - Coculture Techniques MH - Endothelial Cells/cytology/metabolism MH - Fetus MH - Gene Expression Profiling MH - Hepatic Stellate Cells/cytology/metabolism MH - Hepatocytes/cytology/metabolism MH - Humans MH - Immunophenotyping MH - Induced Pluripotent Stem Cells/*cytology MH - Liver/*cytology/metabolism MH - Liver Regeneration MH - Mice MH - Phenotype PMC - PMC5549957 OTO - NOTNLM OT - hepatic stellate cells OT - liver bud OT - liver development OT - liver progenitor cells OT - liver sinusoidal endothelial cells OT - pluripotent stem cells EDAT- 2017/08/02 06:00 MHDA- 2018/04/24 06:00 PMCR- 2017/07/27 CRDT- 2017/08/01 06:00 PHST- 2017/01/14 00:00 [received] PHST- 2017/06/22 00:00 [revised] PHST- 2017/06/23 00:00 [accepted] PHST- 2017/08/02 06:00 [pubmed] PHST- 2018/04/24 06:00 [medline] PHST- 2017/08/01 06:00 [entrez] PHST- 2017/07/27 00:00 [pmc-release] AID - S2213-6711(17)30273-4 [pii] AID - 10.1016/j.stemcr.2017.06.010 [doi] PST - ppublish SO - Stem Cell Reports. 2017 Aug 8;9(2):490-498. doi: 10.1016/j.stemcr.2017.06.010. Epub 2017 Jul 27.