Lactate promotes survival and hepatocyte differentiation of human induced pluripotent stem cells in a medium without glucose and supplemented with galactose

Tomizawa,Minoru; Shinozaki,Fuminobu; Mikata,Takashi; Tanno,Hiroyuki; Shigeta,Midori

doi:10.3892/br.2023.1672

Lactate promotes survival and hepatocyte differentiation of human induced pluripotent stem cells in a medium without glucose and supplemented with galactose

Authors:
- Minoru Tomizawa
- Fuminobu Shinozaki
- Takashi Mikata
- Hiroyuki Tanno
- Midori Shigeta
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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 Neurosurgery, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan, Department of Pediatrics, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan
Published online on: October 6, 2023 https://doi.org/10.3892/br.2023.1672
Article Number: 90

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Abstract

Human induced pluripotent stem (iPS) cells initiate hepatocyte differentiation in a medium without glucose and supplemented with galactose, oncostatin M and small molecules [hepatocyte differentiation inducer (HDI)]. To clarify the metabolic differences between iPS cells in HDI and ReproFF (undifferentiated state), a metabolome analysis was performed. iPS cells were cultured in a medium without glucose and supplemented with galactose, as well as 1 mM of calcium lactate, sodium lactate or lactic acid. After 7 days of culture, the cells were subjected to reverse transcription‑quantitative PCR analysis. The galactose‑1‑phosphate concentration was significantly higher in cells cultured in HDI than in those cultured with ReproFF. The lactate concentration in the HDI group was significantly lower than that in the ReproFF group. The expression levels of α‑feto protein and albumin were significantly higher in the groups cultured with calcium lactate, sodium lactate and lactic acid as compared with ReproFF. It was suggested that lactate promoted the survival of iPS cells cultured in a medium without glucose and supplemented with galactose. Under these conditions, iPS cells begin to differentiate into a hepatocyte lineage. Lactate may be applied to produce hepatocytes from iPS cells more efficiently.

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