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Galactosylated collagen matrix enhanced in vitro maturation of human embryonic stem cell-derived hepatocyte-like cells

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Abstract

Due to their important biomedical applications, functional human embryonic stem cell-derived hepatocyte-like cells (hESC-HLCs) are an attractive topic in the field of stem cell differentiation. Here, we have initially differentiated hESCs into functional hepatic endoderm (HE) and continued the differentiation by replating them onto galactosylated collagen (GC) and collagen matrices. The differentiation of hESC-HE cells into HLCs on GC substrate showed significant up-regulation of hepatic-specific genes such as ALB, HNF4α, CYP3A4, G6P, and ASGR1. There was more albumin secretion and urea synthesis, as well as more cytochrome p450 activity, in differentiated HLCs on GC compared to the collagen-coated substrate. These results suggested that GC substrate has the potential to be used for in vitro maturation of hESC-HLCs.

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Acknowledgments

This study was funded by a grant provided from Royan Institute and supported by the National Science Council (NSC) of Taiwan, Research Grant of NSC 102-2221-E-011-010.

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Authors and Affiliations

  1. Department of Stem Cells and Developmental Biology at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran

    Arefeh Ghodsizadeh, Abbas Piryaei, Behshad Pournasr, Mostafa Najarasl & Hossein Baharvand

  2. Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran

    Arefeh Ghodsizadeh

  3. Centre of Excellence in Nanotechnology, Taipei Medical University, Taipei, 110, Taiwan

    Hossein Hosseinkhani

  4. Graduate Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei, 110, Taiwan

    Hossein Hosseinkhani

  5. Department of Biology and Anatomical Sciences, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Abbas Piryaei

  6. Life Science Laboratory, Nitta Gelatin Inc., Osaka, 581-0024, Japan

    Yosuke Hiraoka

  7. Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran

    Hossein Baharvand

Authors
  1. Arefeh Ghodsizadeh
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  2. Hossein Hosseinkhani
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  3. Abbas Piryaei
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  4. Behshad Pournasr
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  5. Mostafa Najarasl
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  6. Yosuke Hiraoka
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  7. Hossein Baharvand
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Corresponding author

Correspondence to Hossein Baharvand.

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Ghodsizadeh, A., Hosseinkhani, H., Piryaei, A. et al. Galactosylated collagen matrix enhanced in vitro maturation of human embryonic stem cell-derived hepatocyte-like cells. Biotechnol Lett 36, 1095–1106 (2014). https://doi.org/10.1007/s10529-014-1454-0

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  • DOI: https://doi.org/10.1007/s10529-014-1454-0

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