Transdifferentiation of human islet cells in a long-term culture

Bruno M. Schmied, Alexis Ulrich, Hosei Matsuzaki, Xianzhong Ding, Camillo Ricordi, Lamont Weide, Mary Pat Moyer, Surinder K. Batra, Thomas E. Adrian, Parviz M. Pour

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

It has been established that ductal cells or precursor cells within the ductal tree of the pancreas can differentiate into islet cells. Although islet cells can also form exocrine cells, it is unclear whether they arise from precursor (stem) cells or from mature endocrine cells by transdifferentiation. Using a defined culture medium and technique for islet purification, for the first time we were able to maintain human islets in culture for more than a year. Multilabeling immunohistochemical and immunoelectron microscopic examination of the islets at different days of culture using islet cell markers (antibodies to hormones, neuron-specific enolase, chromogranin A) and ductal cell markers (cytokeratins 7 and 19, carbonic anhydrase II, DU-PAN2, CA 19-9, and MUC1) revealed that endocrine cells gradually transdifferentiate to ductal, acinar, and intermediary cells. Although islet hormone secretion ceased after day 28 in culture, endocrine cells were still detectable at day 60. However, later, all endocrine and exocrine cells were replaced by undifferentiated cells that expressed neuron-specific enolase, chromogranin A, laminin, vimentin, cytokeratin 7 and 19, α-l-antitrypsin, transforming growth factor-α, and epidermal growth factor receptor. Our data thus show that, under proper conditions, human islets can be maintained in vitro over a long period and that, in the culture condition, islet cells seem to transdifferentiate to exocrine cells and undifferentiated cells, which may be considered pancreatic precursor (stem) cells.

Original languageEnglish (US)
Pages (from-to)157-171
Number of pages15
JournalPancreas
Volume23
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Culture
  • Differentiation
  • Islet
  • Markers

ASJC Scopus subject areas

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

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    Schmied, B. M., Ulrich, A., Matsuzaki, H., Ding, X., Ricordi, C., Weide, L., Moyer, M. P., Batra, S. K., Adrian, T. E., & Pour, P. M. (2001). Transdifferentiation of human islet cells in a long-term culture. Pancreas, 23(2), 157-171. https://doi.org/10.1097/00006676-200108000-00006