Differentiation of islet cells in long-term culture

Bruno M. Schmied, Guozhen Liu, Hosei Matsuzaki, Alexis Ulrich, Sara Hernberg, Mary Pat Moyer, Lemont Weide, Leo Murphy, Surinder K. Batra, Parviz M. Pour

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Our previous studies in the hamster pancreatic cancer model have shown that exocrine pancreatic cancer arises from ductal/ductular cells, as well as from within the islets, most probably from islet precursor (stem) cells. To identify and characterize these cells, we established a long-term culture from isolated hamster islets and investigated their growth, differentiation, and expression of biomarkers. Islets maintained their original form and structure within the first 14 days in culture. However, beginning at day 7, ductular structures began to form within the islets. At day 21 in culture, acinar cells, intermediary cells, oncocytes, and cells comparable to pancreatic hepatocytes also appeared between ductular and endocrine cells. The number of duct-like cells gradually increased, whereas the number of hormone-producing cells decreased. After 35 days in culture, the exocrine cells disappeared, and undifferentiated cells formed a monolayer. These cells expressed cytokeratins, α1-antitrypsin, transforming growth factor-α, epidermal growth factor receptor, carbonic anhydrase II, vimentin, laminin, and showed binding to tomato lectin and Phaseolus vulgaris leukoagglutinin. They did not express the regulatory transcriptional factors; insulin- promoting factor 1, NKx6.1, Pax6, and NeuroD. The results thus indicate that islet cells have potential to form exocrine cells. At present, it is not clear whether these cells originate from preexisting stem cells or from transdifferentiated islet cells.

Original languageEnglish (US)
Pages (from-to)337-347
Number of pages11
JournalPancreas
Volume20
Issue number4
DOIs
StatePublished - May 2000

Keywords

  • Acinar
  • Differentiation
  • Ductular cells
  • Hamster
  • Intermediary
  • Islets

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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