Differentiation of adult hepatic stem-like cells into pancreatic endocrine cells

Satoko Yamada, Kunihiko Terada, Yasuharu Ueno, Toshihiro Sugiyama, Masaharu Seno, Itaru Kojima

Research output: Contribution to journalArticle

Abstract

To apply cell transplantation for treatment of diabetes mellitus, a sufficient number of β-cell sources are required. In the present study, we examined whether an epithelial cell line obtained from normal adult rat liver, namely hepatic stem-like (HSL) cells, which can be converted to both hepatocytes and billiary epithelial cells, could be a potential β-cell source. The growth speed of HSL cells was rapid and these cells were easily expanded in vitro. Bipotential hepatic stem cells, HSL cells, also expressed PGP9.5, which is expressed in neurons, β-cells, and progenitor cells of the pancreatic endocrine cells as well. Sodium butyrate induced morphological changes in HSL cells and converted them into flattened cells with large cytoplasm. When HSL cells were incubated with a combination of 5 mM sodium butyrate and 1 nM betacellulin, most of the cells were converted into morphologically neuron-like cells. RT-PCR analysis revealed that a series of transcriptional factors involved in differentiation of pancreatic endocrine cells was induced by the treatment with sodium butyrate and betacellulin. mRNAs for insulin, pancreatic polypeptide, and somatostatin were also observed. Immunoreactive pancreatic polypeptide, somatostatin, and insulin were detected in sodium butyrate and betacellulin-treated HSL cells. In conclusion, HSL cells obtained from adult normal liver also have the potential to differentiate into pancreatic endocrine cells in vitro. HSL cells may be one of the potential β-cell sources for cell transplant therapy for insulin-dependent diabetes.

Original languageEnglish
Pages (from-to)647-653
Number of pages7
JournalCell Transplantation
Volume14
Issue number9
Publication statusPublished - Jan 1 2005

Keywords

  • Endocrine cell differentiation
  • Hepatic stem-like cell
  • Insulin
  • Liver epithelial cell

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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  • Cite this

    Yamada, S., Terada, K., Ueno, Y., Sugiyama, T., Seno, M., & Kojima, I. (2005). Differentiation of adult hepatic stem-like cells into pancreatic endocrine cells. Cell Transplantation, 14(9), 647-653.