An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells
Summary: 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 ma...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-08-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117302734 |
| _version_ | 1818020865140326400 |
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| author | Yuta Koui Taketomo Kido Toshimasa Ito Hiroki Oyama Shin-Wei Chen Yuki Katou Katsuhiko Shirahige Atsushi Miyajima |
| author_facet | Yuta Koui Taketomo Kido Toshimasa Ito Hiroki Oyama Shin-Wei Chen Yuki Katou Katsuhiko Shirahige Atsushi Miyajima |
| author_sort | Yuta Koui |
| collection | DOAJ |
| description | Summary: 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 β 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. : Koui et al. developed efficient methods for generating LSEC and HSC from human iPS cells. These cells exhibit distinctive phenotypes and promote proliferation and differentiation of LPCs. They are useful for generation of functional liver tissue that can be utilized in drug discovery, toxicology, and disease modeling in vitro. Keywords: liver bud, liver sinusoidal endothelial cells, hepatic stellate cells, liver progenitor cells, liver development, pluripotent stem cells |
| first_indexed | 2024-04-14T08:11:09Z |
| format | Article |
| id | doaj.art-99d9ec9455df420abea6bef012ae3488 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-14T08:11:09Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-99d9ec9455df420abea6bef012ae34882022-12-22T02:04:33ZengElsevierStem Cell Reports2213-67112017-08-0192490498An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal CellsYuta Koui0Taketomo Kido1Toshimasa Ito2Hiroki Oyama3Shin-Wei Chen4Yuki Katou5Katsuhiko Shirahige6Atsushi Miyajima7Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, JapanLaboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan; Corresponding authorLaboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, JapanLaboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, JapanLaboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, JapanLaboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, JapanLaboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, JapanLaboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan; Corresponding authorSummary: 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 β 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. : Koui et al. developed efficient methods for generating LSEC and HSC from human iPS cells. These cells exhibit distinctive phenotypes and promote proliferation and differentiation of LPCs. They are useful for generation of functional liver tissue that can be utilized in drug discovery, toxicology, and disease modeling in vitro. Keywords: liver bud, liver sinusoidal endothelial cells, hepatic stellate cells, liver progenitor cells, liver development, pluripotent stem cellshttp://www.sciencedirect.com/science/article/pii/S2213671117302734 |
| spellingShingle | Yuta Koui Taketomo Kido Toshimasa Ito Hiroki Oyama Shin-Wei Chen Yuki Katou Katsuhiko Shirahige Atsushi Miyajima An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells Stem Cell Reports |
| title | An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells |
| title_full | An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells |
| title_fullStr | An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells |
| title_full_unstemmed | An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells |
| title_short | An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells |
| title_sort | in vitro human liver model by ipsc derived parenchymal and non parenchymal cells |
| url | http://www.sciencedirect.com/science/article/pii/S2213671117302734 |
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