Hepatic differentiation of mouse iPS cells in vitro

Masaya Iwamuro, Toshiyuki Komaki, Yasuhiro Kubota, Masayuki Seita, Hironobu Kawamoto, Takeshi Yuasa, Javed M. Shahid, Reham A R A Hassan, Wael A R A Hassan, Shuhei Nakaji, Yuriko Nishikawa, Eisaku Kondo, Kazuhide Yamamoto, Ira J. Fox, Naoya Kobayashi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Induced pluripotent stem (iPS) cells are pluripotent and are able to unlimitedly proliferate in vitro. This technical breakthrough in creating iPS cells from somatic cells has noteworthy implications for overcoming the immunological rejection and the ethical issues associated with the derivation of embryonic stem cells from embryos. In the current work, we present an efficient hepatic differentiation of mouse iPS cells in vitro. iPS cells were cultured free floating to induce the formation of embryoid bodies (EB) for 5 days. EB were transferred to a gelatin-coated plate and treated with 100 ng/ml activin A and 100 ng/ml basic fibroblast growth factor (bFGF) for 3 days to induce definitive endoderm. Cells were further cultured for 8 days with 100 ng/ml hepatocyte growth factor (HGF) to generate hepatocytes. Characterization was performed by RT-PCR assay. Functional analysis for albumin secretion and ammonia removal was also carried out. iPS cell-derived hepatocyte-like cells (iPS-Heps) were obtained at the end of the differentiation program. Expression levels of a gestational hepatocyte gene and lineage-specific hepatic genes intensified in iPS-Heps. The production of albumin increased in a time-dependent manner. iPS-Heps were capable of metabolizing ammonia. We present here instant hepatic differentiation of mouse iPS cells using combined 3-day treatments of activin A and bFGF with subsequent 8-day HGF. Our study will be an important step to generate hepatocytes from human iPS cells as a new source for liver-targeted cell therapies.

Original languageEnglish
Pages (from-to)841-847
Number of pages7
JournalCell Transplantation
Volume19
Issue number6-7
DOIs
Publication statusPublished - 2010

Fingerprint

Induced Pluripotent Stem Cells
Stem cells
Liver
Hepatocytes
Embryoid Bodies
Hepatocyte Growth Factor
Fibroblast Growth Factor 2
Fibroblasts
Ammonia
Fibroblast Growth Factor 3
Albumins
Genes
Functional analysis
Endoderm
In Vitro Techniques
Gelatin
Embryonic Stem Cells
Cell- and Tissue-Based Therapy
Ethics
Assays

Keywords

  • Hepatic differentiation
  • Hepatocytes
  • Induced pluripotent stem (iPS) cells

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Iwamuro, M., Komaki, T., Kubota, Y., Seita, M., Kawamoto, H., Yuasa, T., ... Kobayashi, N. (2010). Hepatic differentiation of mouse iPS cells in vitro. Cell Transplantation, 19(6-7), 841-847. https://doi.org/10.3727/096368910X508960

Hepatic differentiation of mouse iPS cells in vitro. / Iwamuro, Masaya; Komaki, Toshiyuki; Kubota, Yasuhiro; Seita, Masayuki; Kawamoto, Hironobu; Yuasa, Takeshi; Shahid, Javed M.; Hassan, Reham A R A; Hassan, Wael A R A; Nakaji, Shuhei; Nishikawa, Yuriko; Kondo, Eisaku; Yamamoto, Kazuhide; Fox, Ira J.; Kobayashi, Naoya.

In: Cell Transplantation, Vol. 19, No. 6-7, 2010, p. 841-847.

Research output: Contribution to journalArticle

Iwamuro, M, Komaki, T, Kubota, Y, Seita, M, Kawamoto, H, Yuasa, T, Shahid, JM, Hassan, RARA, Hassan, WARA, Nakaji, S, Nishikawa, Y, Kondo, E, Yamamoto, K, Fox, IJ & Kobayashi, N 2010, 'Hepatic differentiation of mouse iPS cells in vitro', Cell Transplantation, vol. 19, no. 6-7, pp. 841-847. https://doi.org/10.3727/096368910X508960
Iwamuro M, Komaki T, Kubota Y, Seita M, Kawamoto H, Yuasa T et al. Hepatic differentiation of mouse iPS cells in vitro. Cell Transplantation. 2010;19(6-7):841-847. https://doi.org/10.3727/096368910X508960
Iwamuro, Masaya ; Komaki, Toshiyuki ; Kubota, Yasuhiro ; Seita, Masayuki ; Kawamoto, Hironobu ; Yuasa, Takeshi ; Shahid, Javed M. ; Hassan, Reham A R A ; Hassan, Wael A R A ; Nakaji, Shuhei ; Nishikawa, Yuriko ; Kondo, Eisaku ; Yamamoto, Kazuhide ; Fox, Ira J. ; Kobayashi, Naoya. / Hepatic differentiation of mouse iPS cells in vitro. In: Cell Transplantation. 2010 ; Vol. 19, No. 6-7. pp. 841-847.
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