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Differentiation of Embryonic Stem Cells into Endoderm-Derived Hepatocytes

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Stem Cells and Cancer Stem Cells, Volume 6

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 6))

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Abstract

Embryonic stem (ES) cells are defined as unspecialized cells that are self-renewing pluripotent cells and have the capability to differentiate into wide variety of cell types. This potentiality represents a promising source to overcome many human diseases by providing an unlimited supply of all cell types, including cells with hepatic characteristics. Although, many efforts are currently underway to induce endoderm-derived hepatocytes from embryonic stem cells, the preparation of specific lineages at high purity remains in challenge. Thus, a major goal is to develop new culture based approaches, using advanced biomaterials, to differentiate the pluripotent cells into homogeneous population of hepatocytes, and to monitor liver developmental pathways in a precise and near-physiological fashion. Bridging of cell biological and biomaterials technologies promises to develop a variety of new applications that will advance stem-cell based approaches into regenerative medicine.

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References

  • Agarwal S, Holton KL, Lanza R (2008) Efficient differentiation of functional hepatocytes from human embryonic stem cells. Stem Cells 26:1117–1127

    Article  PubMed  CAS  Google Scholar 

  • Baharvand H, Hashemi SM, Kazemi Ashtiani S, Farrokhi A (2006) Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro. Int J Dev Biol 50:645–652

    Article  PubMed  CAS  Google Scholar 

  • Basma H, Soto-Gutierrez A, Yannam GR, Liu L, Ito R, Yamamoto T, Ellis E, Carson SD, Sato S, Chen Y, Muirhead D, Navarro-Alvarez N, Wong RJ, Roy-Chowdhury J, Platt JL, Mercer DF, Miller JD, Strom SC, Kobayashi N, Fox IJ (2009) Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology 136:990–999

    Article  PubMed  CAS  Google Scholar 

  • Cai J, Zhao Y, Liu Y, Ye F, Song Z, Qin H, Meng S, Chen Y, Zhou R, Song X, Guo Y, Ding M, Deng H (2007) Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology 45:1229–1239

    Article  PubMed  CAS  Google Scholar 

  • D’Amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE (2005) Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23:1534–1541

    Article  PubMed  Google Scholar 

  • Dasgupta A, Hughey R, Lancin P, Larue L, Moghe PV (2005) E-cadherin synergistically induces hepatospecific phenotype and maturation of embryonic stem cells in conjunction with hepatotrophic factors. Biotechnol Bioeng 92:257–266

    Article  PubMed  CAS  Google Scholar 

  • Fair JH, Cairns BA, Lapaglia M, Wang J, Meyer AA, Kim H, Hatada S, Smithies O, Pevny L (2003) Induction of hepatic differentiation in embryonic stem cells by co-culture with embryonic cardiac mesoderm. Surgery 134:189–196

    Article  PubMed  Google Scholar 

  • Gouon-Evans V, Boussemart L, Gadue P, Nierhoff D, Koehler CI, Kubo A, Shafritz DA, Keller G (2006) BMP-4 is required for hepatic specification of mouse embryonic stem cell-derived definitive endoderm. Nat Biotechnol 24:1402–1411

    Article  PubMed  CAS  Google Scholar 

  • Guertin M, Baril P, Bartkowiak J, Anderson A, Belanger L (1983) Rapid suppression of alpha 1-fetoprotein gene transcription by dexamethasone in developing rat liver. Biochemistry 22:4296–4302

    Article  PubMed  CAS  Google Scholar 

  • Haque A, Nagaoka M, Hexig B, Akaike T (2010) Artificial extracellular matrix for embryonic stem cell cultures: a new frontier of nanobiomaterials. Sci Technol Adv Mater 11:1–9

    Article  Google Scholar 

  • Haque A, Hexig B, Meng Q, Hossain S, Nagaoka M, Akaike T (2011) The effect of recombinant E-cadherin substratum on the differentiation of endoderm-derived hepatocyte-like cells from embryonic stem cells. Biomaterials 32:2032–2042

    Article  PubMed  CAS  Google Scholar 

  • Hay DC, Fletcher J, Payne C, Terrace JD, Gallagher RC, Snoeys J, Black JR, Wojtacha D, Samuel K, Hannoun Z, Pryde A, Filippi C, Currie IS, Forbes SJ, Ross JA, Newsome PN, Iredale JP (2008) Highly efficient differentiation of hESCs to functional hepatic endoderm requires Activin A and Wnt3a signaling. Proc Natl Acad Sci USA 105:12301–12306

    Article  PubMed  CAS  Google Scholar 

  • Ishizaka S, Shiroi A, Kanda S, Yoshikawa M, Tsujinoue H, Kuriyama S, Hasuma T, Nakatani K, Takahashi K (2002) Development of hepatocytes from ES cells after transfection with the HNF-3β gene. FASEB J 16:1444–1446

    PubMed  CAS  Google Scholar 

  • Kamiya A, Kinoshita T, Miyajima A (2001) Oncostatin M and hepatocyte growth factor induce hepatic maturation via distinct signaling pathways. FEBS Lett 492:90–94

    Article  PubMed  CAS  Google Scholar 

  • Kinoshita T, Miyajima A (2002) Cytokine regulation of liver development. Biochim Biophys Acta 1592:303–312

    Article  PubMed  CAS  Google Scholar 

  • Kuai XL, Cong XQ, Li XL, Xiao SD (2003) Generation of hepatocytes from cultured mouse embryonic stem cells. Liver Transpl 9:1094–1099

    Article  PubMed  Google Scholar 

  • Kubo A, Shinozaki K, Shannon JM, Kouskoff V, Kennedy M, Woo S, Fehling HJ, Keller G (2004) Development of definitive endoderm from embryonic stem cells in culture. Development 131:1651–1662

    Article  PubMed  CAS  Google Scholar 

  • Kung JW, Forbes SJ (2009) Stem cells and liver repair. Curr Opin Biotechnol 20:568–574

    Article  PubMed  CAS  Google Scholar 

  • Lee JY, Tuleuova N, Jones CN, Ramanculov E, Zern MA, Revzin A (2009) Directing hepatic differentiation of embryonic stem cells with protein microarray-based co-cultures. Integr Biol 1:460–468

    Article  CAS  Google Scholar 

  • Liu T, Zhang S, Chen X, Li G, Wang Y (2010) Hepatic differentiation of mouse embryonic stem cells in three-dimensional polymer scaffolds. Tissue Eng Part A 16:1115–1122

    Article  PubMed  CAS  Google Scholar 

  • Lutolf MP, Hubbell JA (2005) Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 23:47–55

    Article  PubMed  CAS  Google Scholar 

  • Moore RN, Dasgupta A, Rajaei N, Yarmush ML, Toner M, Larue L, Moghe PV (2008) Enhanced differentiation of embryonic stem cells using co-cultivation with hepatocytes. Biotechnol Bioeng 101:1332–1343

    Article  PubMed  CAS  Google Scholar 

  • Nagaoka M, Koshimizu U, Yuasa S, Hattori F, Chen H, Tanaka T, Okabe M, Fukuda K, Akaike T (2006) E-cadherin-coated plates maintain pluripotent ES cells without colony formation. PLoS One 1:e15

    Article  PubMed  Google Scholar 

  • Nagaoka M, Hagiwara Y, Takemura K, Murakami Y, Li J, Duncan SA, Akaike T (2008) Design of the artificial acellular feeder layer for the efficient propagation of mouse embryonic stem cells. J Biol Chem 283:26468–26476

    Article  PubMed  CAS  Google Scholar 

  • Nishikawa S, Jakt LM, Era T (2007) Embryonic stem-cell culture as a tool for developmental cell biology. Nature 8:502–507

    CAS  Google Scholar 

  • Parashurama N, Nahmias Y, Cho CH, Poll VD, Tilles AW, Berthiaume F, Berthiaume F, Yarmush ML (2008) Activin alters the kinetics of endoderm induction in embryonic stem cells cultured on collagen gels. Stem Cells 26:474–484

    Article  PubMed  CAS  Google Scholar 

  • Rossant J, Tam PP (2004) Emerging asymmetry and embryonic patterning in early mouse development. Dev Cell 7:155–164

    Article  PubMed  CAS  Google Scholar 

  • Schrem H, Klempnauer J, Borlak J (2002) Liver-enriched transcription factors in liver function and development. Part I: the hepatocyte nuclear factor network and liver-specific gene expression. Pharmacol Rev 54:129–158

    Article  PubMed  CAS  Google Scholar 

  • Shiraki N, Umeda K, Sakashita N, Takeya M, Kume K, Kume S (2008) Differentiation of mouse and human embryonic stem cells into hepatic lineages. Genes Cells 13:731–746

    Article  PubMed  CAS  Google Scholar 

  • Snykers S, De Kock J, Rogiers V, Vanhaecke T (2009) In vitro differentiation of embryonic and adult stem cells into hepatocytes: state of the art. Stem Cells 27:577–605

    Article  PubMed  CAS  Google Scholar 

  • Soto-Gutierrez A, Navarro-Alvarez N, Zhao D, Rivas-Carrillo JD, Lebkowski J, Tanaka N, Fox IF, Kobayashi N (2007) Differentiation of mouse embryonic stem cells to hepatocyte-like cells by co-culture with human liver nonparenchymal cell lines. Nat Protoc 2:347–356

    Article  PubMed  CAS  Google Scholar 

  • Tada S, Era T, Furusawa C, Sakurai H, Nishikawa S, Kinoshita M, Nakao K, Chiba T, Nishikawa S (2005) Characterization of mesendoderm: a diverging point of the definitive endoderm and mesoderm in embryonic stem cell differentiation culture. Development 132:4363–4374

    Article  PubMed  CAS  Google Scholar 

  • Tanaka M, Itoh T, Tanimizu N, Miyajima A (2011) Liver stem/progenitor cells: their characteristics and regulatory mechanisms. J Biochem 149:231–239

    Article  PubMed  CAS  Google Scholar 

  • Touboul T, Hannan NR, Corbineau S, Martinez A, Martinet C, Branchereau S, Mainot S, Strick-Marchand H, Pedersen R, Di Santo J, Weber A, Vallier L (2010) Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology 51:1754–1765

    Article  PubMed  CAS  Google Scholar 

  • Tsukada Y, Nagaki M, Suetsugu A, Osawa Y, Moriwaki H (2009) Extracellular matrix is required for the survival and differentiation of transplanted hepatic progenitor cells. Biochem Biophys Res Commun 381:733–737

    Article  PubMed  CAS  Google Scholar 

  • Yasunaga M, Tada S, Torikai-Nishikawa S, Nakano Y, Okada M, Jakt LM, Nishikawa S, Chiba T, Era T, Nishikawa S (2005) Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells. Nat Biotechnol 23:1542–1550

    Article  PubMed  CAS  Google Scholar 

  • Zhao D, Chen S, Cai J, Guo Y, Song Z, Che J, Liu C, Wu C, Ding M, Den H (2009) Derivation and characterization of hepatic progenitor cells from human embryonic stem cells. PLoS One 4:e6468

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Akaike Lab, Department of Bimolecular Engineering, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan

    Amranul Haque

  2. Frontier Research Center, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan

    Toshihiro Akaike

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  1. Amranul Haque
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  2. Toshihiro Akaike
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Correspondence to Toshihiro Akaike .

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  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

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Haque, A., Akaike, T. (2012). Differentiation of Embryonic Stem Cells into Endoderm-Derived Hepatocytes. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 6. Stem Cells and Cancer Stem Cells, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2993-3_6

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