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Differentiation of human embryonic stem cells to hepatocyte-like cells on a new developed xeno-free extracellular matrix

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Abstract

Human embryonic stem cells (hESCs) provide a new source for hepatocyte production in translational medicine and cell replacement therapy. The reported hESC-derived hepatocyte-like cells (HLCs) were commonly generated on Matrigel, a mouse cell line-derived extracellular matrix (ECM). Here, we performed the hepatic lineage differentiation of hESCs following a stepwise application of growth factors on a newly developed serum- and xeno-free, simple and cost-benefit ECM, designated “RoGel,” which generated from a modified conditioned medium of human fibroblasts. In comparison with Matrigel, the differentiated HLCs on both ECMs expressed similar levels of hepatocyte-specific genes, secreted α-fetoprotein, and metabolized ammonia, showed glycogen storage activity as well as low-density lipoprotein and indocyanine green uptake. The transplantation of hESC–HLCs into the carbon tetrachloride-injured liver demonstrated incorporation of the cells into the host mouse liver and the expression of albumin. The results suggest that the xeno-free and cost-benefit matrix may be applicable in bioartificial livers and also may facilitating a clinical application of human pluripotent stem cell-derived hepatocytes in the future.

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Acknowledgments

We appreciate MR Larijani for his technical support. This study was funded by the Department of Stem Cells and Developmental Biology at Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Conflict of interest

The authors declare that they have no competing financial interests.

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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, PO Box 19395-4644, Tehran, Iran

    Zahra Farzaneh, Mohammad Pakzad, Massoud Vosough, Behshad Pournasr & Hossein Baharvand

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

    Hossein Baharvand

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  1. Zahra Farzaneh
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  2. Mohammad Pakzad
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  3. Massoud Vosough
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  4. Behshad Pournasr
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  5. Hossein Baharvand
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Correspondence to Hossein Baharvand.

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Farzaneh, Z., Pakzad, M., Vosough, M. et al. Differentiation of human embryonic stem cells to hepatocyte-like cells on a new developed xeno-free extracellular matrix. Histochem Cell Biol 142, 217–226 (2014). https://doi.org/10.1007/s00418-014-1183-4

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