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2015 | Online First | Chapter

Generation and In Vitro Expansion of Hepatic Progenitor Cells from Human iPS Cells

Authors : Ayaka Yanagida, Hiromitsu Nakauchi, Akihide Kamiya, Ph.D.

Published in: Methods in Molecular Biology™

Publisher: Springer New York

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Abstract

Stem cells have the unique properties of self-renewal and multipotency (producing progeny belonging to two or more lineages). Induced pluripotent stem (iPS) cells can be generated from somatic cells by simultaneous expression of pluripotent factors (Oct3/4, Klf4, Sox2, and c-Myc). They share the same properties as embryonic stem (ES) cells and can differentiate into several tissue cells, i.e., neurons, hematopoietic cells, and liver cells. Therefore, iPS cells are suitable candidate cells for regenerative medicine and analyses of disease mechanisms.
The liver is the major organ that regulates a multitude of metabolic functions. Hepatocytes are the major cell type populating the liver parenchyma and express several metabolic enzymes that are necessary for liver functions. Although hepatocytes are essential for maintaining homeostasis, it is difficult to alter artificial and transplanted cells because of their multifunctionality, donor shortage, and immunorejection risk. During liver development, hepatic progenitor cells in the fetal liver differentiate into both mature hepatocytes and cholangiocytes. As hepatic progenitor cells have bipotency and high proliferation ability, they could present a potential source for generating transplantable cells or as a liver study model. Here we describe the induction and purification of hepatic progenitor cells derived from human iPS cells. These cells can proliferate for a long term under suitable culture conditions.
Literature
1.
go back to reference Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872PubMedCrossRef Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872PubMedCrossRef
2.
go back to reference Nakagawa M, Koyanagi M, Tanabe K et al (2007) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26:101–106PubMedCrossRef Nakagawa M, Koyanagi M, Tanabe K et al (2007) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26:101–106PubMedCrossRef
3.
go back to reference Gerbal-Chaloin S, Funakoshi N, Caillaud A et al (2014) Human induced pluripotent stem cells in hepatology. Am J Pathol 184:332–347PubMedCrossRef Gerbal-Chaloin S, Funakoshi N, Caillaud A et al (2014) Human induced pluripotent stem cells in hepatology. Am J Pathol 184:332–347PubMedCrossRef
4.
go back to reference Lemaigre FP (2009) Mechanisms of liver development: concepts for understanding liver disorders and design of novel therapies. Gastroenterology 137:62–79PubMedCrossRef Lemaigre FP (2009) Mechanisms of liver development: concepts for understanding liver disorders and design of novel therapies. Gastroenterology 137:62–79PubMedCrossRef
5.
go back to reference Si-Tayeb K, Lemaigre FP, Duncan SA (2010) Organogenesis and development of the liver. Dev Cell 18:175–189PubMedCrossRef Si-Tayeb K, Lemaigre FP, Duncan SA (2010) Organogenesis and development of the liver. Dev Cell 18:175–189PubMedCrossRef
6.
go back to reference Rossi JM (2001) Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. Gene Dev 15:1998–2009PubMedPubMedCentralCrossRef Rossi JM (2001) Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. Gene Dev 15:1998–2009PubMedPubMedCentralCrossRef
7.
go back to reference Jung J (1999) Initiation of mammalian liver development from endoderm by fibroblast growth factors. Science 284:1998–2003PubMedCrossRef Jung J (1999) Initiation of mammalian liver development from endoderm by fibroblast growth factors. Science 284:1998–2003PubMedCrossRef
8.
go back to reference Tanimizu N (2003) Isolation of hepatoblasts based on the expression of Dlk/Pref-1. J Cell Sci 116:1775–1786PubMedCrossRef Tanimizu N (2003) Isolation of hepatoblasts based on the expression of Dlk/Pref-1. J Cell Sci 116:1775–1786PubMedCrossRef
9.
go back to reference Watanabe T, Nakagawa K, Ohata S et al (2002) SEK1/MKK4-mediated SAPK/JNK signaling participates in embryonic hepatoblast proliferation via a pathway different from NF-κB-induced anti-apoptosis. Dev Biol 250:332–347PubMedCrossRef Watanabe T, Nakagawa K, Ohata S et al (2002) SEK1/MKK4-mediated SAPK/JNK signaling participates in embryonic hepatoblast proliferation via a pathway different from NF-κB-induced anti-apoptosis. Dev Biol 250:332–347PubMedCrossRef
10.
go back to reference Kakinuma S, Ohta H, Kamiya A et al (2009) Analyses of cell surface molecules on hepatic stem/progenitor cells in mouse fetal liver. J Hepatol 51:127–138PubMedCrossRef Kakinuma S, Ohta H, Kamiya A et al (2009) Analyses of cell surface molecules on hepatic stem/progenitor cells in mouse fetal liver. J Hepatol 51:127–138PubMedCrossRef
11.
go back to reference Okada K, Kamiya A, Ito K et al (2012) Prospective isolation and characterization of bipotent progenitor cells in early mouse liver development. Stem Cell Dev 21:1124–1133CrossRef Okada K, Kamiya A, Ito K et al (2012) Prospective isolation and characterization of bipotent progenitor cells in early mouse liver development. Stem Cell Dev 21:1124–1133CrossRef
12.
go back to reference Yanagida A, Ito K, Chikada H et al (2013) An in vitro expansion system for generation of human iPS cell-derived hepatic progenitor-like cells exhibiting a bipotent differentiation potential. PloS One 8:e67541PubMedPubMedCentralCrossRef Yanagida A, Ito K, Chikada H et al (2013) An in vitro expansion system for generation of human iPS cell-derived hepatic progenitor-like cells exhibiting a bipotent differentiation potential. PloS One 8:e67541PubMedPubMedCentralCrossRef
13.
go back to reference Takayama N, Nishimura S, Nakamura S et al (2010) Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells. J Exp Med 207:2817–2830PubMedPubMedCentralCrossRef Takayama N, Nishimura S, Nakamura S et al (2010) Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells. J Exp Med 207:2817–2830PubMedPubMedCentralCrossRef
14.
go back to reference Fujioka T, Yasuchika K, Nakamura Y et al (2004) A simple and efficient cryopreservation method for primate embryonic stem cells. Int J Dev Biol 48(10):1149–1154PubMedCrossRef Fujioka T, Yasuchika K, Nakamura Y et al (2004) A simple and efficient cryopreservation method for primate embryonic stem cells. Int J Dev Biol 48(10):1149–1154PubMedCrossRef
15.
go back to reference Si-Tayeb K, Noto FK, Nagaoka M et al (2009) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51:297–305CrossRef Si-Tayeb K, Noto FK, Nagaoka M et al (2009) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51:297–305CrossRef
16.
go back to reference Kamiya A, Kinoshita T, Ito Y et al (1999) Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer. EMBO J 18:2127–2136PubMedPubMedCentralCrossRef Kamiya A, Kinoshita T, Ito Y et al (1999) Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer. EMBO J 18:2127–2136PubMedPubMedCentralCrossRef
Metadata
Title
Generation and In Vitro Expansion of Hepatic Progenitor Cells from Human iPS Cells
Authors
Ayaka Yanagida
Hiromitsu Nakauchi
Akihide Kamiya, Ph.D.
Copyright Year
2015
Publisher
Springer New York
DOI
https://doi.org/10.1007/7651_2015_199