Engraftment potential of spheroid-forming hepatic endoderm derived from human embryonic stem cells

Sung Eun Kim, Su Yeon An, Dong Hun Woo, Jiyou Han, Jong Hyun Kim, Yu Jin Jang, Jeong Sang Son, Hyunwon Yang, Yong Pil Cheon, Jong Hoon Kim

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Transplantation and drug discovery programs for liver diseases are hampered by the shortage of donor tissue. While recent studies have shown that hepatic cells can be derived from human embryonic stem cells (hESCs), few cases have shown selective enrichment of hESC-derived hepatocytes and their integration into host liver tissues. Here we demonstrate that the dissociation and reaggregation procedure after an endodermal differentiation of hESC produces spheroids mainly consisted of cells showing hepatic phenotypes in vitro and in vivo. A combined treatment with Wnt3a and bone morphogenic protein 4 efficiently differentiated hESCs into definitive endoderm in an adherent culture. Dissociation followed by reaggregation of these cells in a nonadherent condition lead to the isolation of spheroid-forming cells that preferentially expressed early hepatic markers from the adherent cell population. Further differentiation of these spheroid cells in the presence of the hepatocyte growth factor, oncostatin M, and dexamethasone produced a highly enriched population of cells exhibiting characteristics of early hepatocytes, including glycogen storage, indocyanine green uptake, and synthesis of urea and albumin. Furthermore, we show that grafted spheroid cells express hepatic features and attenuate the serum aspartate aminotransferase level in a model of acute liver injury. These data suggest that hepatic progenitor cells can be enriched by the spheroid formation of differentiating hESCs and that these cells have engraftment potential to replace damaged liver tissues.

Original languageEnglish
Pages (from-to)1818-1829
Number of pages12
JournalStem cells and development
Volume22
Issue number12
DOIs
Publication statusPublished - 2013 Jun 15

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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    Kim, S. E., An, S. Y., Woo, D. H., Han, J., Kim, J. H., Jang, Y. J., Son, J. S., Yang, H., Cheon, Y. P., & Kim, J. H. (2013). Engraftment potential of spheroid-forming hepatic endoderm derived from human embryonic stem cells. Stem cells and development, 22(12), 1818-1829. https://doi.org/10.1089/scd.2012.0401