Oncostatin M in William's E medium is suitable for initiation of hepatocyte differentiation in human induced pluripotent stem cells

Tomizawa,Minoru; Shinozaki,Fuminobu; Motoyoshi,Yasufumi; Sugiyama,Takao; Yamamoto,Shigenori; Ishige,Naoki

doi:10.3892/mmr.2017.6406

Oncostatin M in William's E medium is suitable for initiation of hepatocyte differentiation in human induced pluripotent stem cells

Authors:
- Minoru Tomizawa
- Fuminobu Shinozaki
- Yasufumi Motoyoshi
- Takao Sugiyama
- Shigenori Yamamoto
- Naoki Ishige
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Affiliations: Department of Gastroenterology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Radiology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Neurology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Rheumatology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Pediatrics, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Neurosurgery, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan
Published online on: March 28, 2017 https://doi.org/10.3892/mmr.2017.6406
Pages: 3088-3092

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Abstract

William's E (WE) is a suitable medium for the differentiation of human induced pluripotent stem (iPS) cells to the hepatocyte lineage. The aim of the present study was to investigate various growth factors in their ability to promote hepatocyte differentiation of iPS cells in WE medium. Human iPS 201B7 cells were cultured in WE medium supplemented with growth factors, and mRNA expression levels and promoter activities of α‑fetoprotein (AFP) and albumin were examined by reverse transcription‑quantitative polymerase chain reaction and luciferase assay, respectively. In addition, time course analysis of AFP mRNA expression was performed in 201B7 cells cultured in WE medium supplemented with oncostatin M. The results demonstrated that mRNA expression levels of AFP were significantly elevated by most growth factors tested as supplements in WE medium, except all‑trans retinoic acid, compared with cells cultured in ReproFF (a medium that maintains pluripotency). The highest increase in AFP mRNA expression levels was observed by oncostatin M stimulation. Albumin mRNA expression levels were increased by all‑trans retinoic acid and insulin‑transferrin‑selenium supplementation in WE medium compared with cells cultured in ReproFF. Oncostatin M supplementation significantly stimulated the promoter activity of the AFP gene, but no growth factor tested significantly stimulated the promoter activity of the albumin gene. By time course analysis, significant increase of AFP mRNA expression was observed on the sixth day post‑stimulation, compared with cells cultured in WE medium alone. In conclusion, the present study demonstrated that oncostatin M supplementation in WE medium was sufficient to initiate hepatocyte differentiation in iPS cells.

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