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In vitro transformation of adult rat hepatic progenitor cells into pancreatic endocrine hormone-producing cells

  • Original Articles
  • Published:
Journal of Hepato-Biliary-Pancreatic Surgery

Abstract

Background/Purpose

Pancreatic and duodenal homeobox factor 1 (Pdx-1) plays an important role in initiating differentiation toward pancreatic endocrine cells. The transdifferentiation or transformation of hepatocytes into pancreatic endocrine cells could be feasible, due to their similar cellular origins. Our goal in this study was to see if small hepatocytes (SHs) could give rise to pancreatic endocrine cells via exogenous Pdx-1 gene expression.

Methods

SHs were cultured for 10 days before adenovirus (Adt)-mediated Pdx-1 gene transfection. We performed western blot analysis for pancreatic transcription factors in the nuclei and reverse-transcription polymerase chain reaction (RT-PCR) for the gene expression of pancreatic endocrine hormones. Confocal laser microscanning analysis was used to observe the transformation of SHs.

Results

Pancreatic transcription factors such as Pdx-1, Ngn3, NeuroD, Nkx2.2, and Pax6 were induced after Adt-Pdx-1 gene transfection. The mRNA expression of pancreatic endocrine hormones (insulin, glucagon, and somatostatin) was induced after the gene transfection. Pdx-1 was expressed in the nucleus, where the cells were positive for one or more of the hormones and cytokeratin (CK) 8. Some cells were positive for multiple hormones. The insulin level increased while the glucagon level decreased after the glucose loading test, depending on the glucose concentration.

Conclusions

SHs are transformed into functional pancreatic endocrine cells after Pdx-1 gene transfection.

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Authors and Affiliations

  1. First Department of Surgery, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan

    Hiroyuki Kawasaki, Toru Mizuguchi, Hideki Oshima, Tadashi Katsuramaki & Koichi Hirata

  2. Department of Pathophysiology, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, Japan

    Yamato Kikkawa & Toshihiro Mitaka

  3. Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, Japan

    Yasushi Sasaki & Takashi Tokino

  4. Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Sapporo, Japan

    Yasuo Kokai

  5. Division of Stem Cell Regulation Research, G6, Osaka University Medical School, Suita, Japan

    Jun-Ichi Miyazaki

Authors
  1. Hiroyuki Kawasaki
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  2. Toru Mizuguchi
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  3. Yamato Kikkawa
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  4. Hideki Oshima
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  5. Yasushi Sasaki
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  6. Takashi Tokino
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  7. Yasuo Kokai
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  8. Jun-Ichi Miyazaki
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  9. Tadashi Katsuramaki
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  10. Toshihiro Mitaka
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  11. Koichi Hirata
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Cite this article

Kawasaki, H., Mizuguchi, T., Kikkawa, Y. et al. In vitro transformation of adult rat hepatic progenitor cells into pancreatic endocrine hormone-producing cells. J Hepatobiliary Pancreat Surg 15, 310–317 (2008). https://doi.org/10.1007/s00534-007-1252-3

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  • DOI: https://doi.org/10.1007/s00534-007-1252-3

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