Activation of Nestin-Positive Duct Stem (NPDS) Cells in Pancreas Upon Neogenic Motivation and Possible Cytodifferentiation into Insulin-Secreting Cells from NPDS Cells

So Yoon Kim, Seung Hee Lee, Byeong Moo Kim, Eun Ho Kim, Bon Hong Min, M. Bendayan, In Sun Park

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Stem cells in adult pancreas and their specific marker are poorly characterized. We hypothesized that pancreatic stem cells could evolve from the duct system in response to neogenic stimulation and may transiently express nestin during tissue regeneration. After partial pancreatectomy (Px), we found extensive formation of ductules consisting of nestin-positive epithelial cells with higher replicating ability in the neogenic foci, particularly at day 3 after Px. Nestin was highly expressed in the earlier stages of ductule morphogenesis and then regressed as the cells evolved toward differentiated pancreatic cell types. The neogenic ductules were isolated for the culture of nestin-positive duct stem cells. These nestin-positive duct cells were numerous and displayed extensive self-replication in the duct cell explants after 2-3 days of culture, thus depicted as nestin-positive duct stem (NPDS) cells. As seen in the tissue of neogenic foci, NPDS cells were negative for cytokeratin-20 and vimentin, the marker for duct epithelial and mesenchymal cells, respectively. Endocrine cells, mostly insulin cells, were present in the explants at day 2 as single cells or as small clusters adjacent to the NPDS cells, and formed islet-like masses at day 3 of culture, suggesting islet cell differentiation from NPDS cells. In addition, insulin secretion from these beta cells responded to glucose stimulation. We found transient up-regulation of PDX-1 expression by reverse transcriptase-polymerase chain reaction at day 3 after Px in pancreatic tissue. Higher expression of PDX-1 was seen in the culture of neogenic ductules than that of ducts isolated from the sham-operated pancreas. In particular, a subpopulation of nestin-positive cells in the duct cell explants formed from the neogenic ductules expressed PDX-1 in their nuclei. Taken together, this information suggests that NPDS cells could be generated from adult pancreas by neogenic motivations and they may differentiate into insulin-secreting cells.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalDevelopmental Dynamics
Volume230
Issue number1
DOIs
Publication statusPublished - 2004 May 1

Fingerprint

Nestin
Insulin-Secreting Cells
Pancreas
Stem Cells
Epithelial Cells
Keratin-20
Insulin
Adult Stem Cells
Pancreatectomy
Endocrine Cells
Vimentin
Reverse Transcriptase Polymerase Chain Reaction
Islets of Langerhans
Morphogenesis
Regeneration
Cell Differentiation
Up-Regulation

Keywords

  • Beta cell
  • Differentiation
  • Duct cells
  • Insulin
  • Neogenesis
  • Nestin
  • Stem cells

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Activation of Nestin-Positive Duct Stem (NPDS) Cells in Pancreas Upon Neogenic Motivation and Possible Cytodifferentiation into Insulin-Secreting Cells from NPDS Cells. / Kim, So Yoon; Lee, Seung Hee; Kim, Byeong Moo; Kim, Eun Ho; Min, Bon Hong; Bendayan, M.; Park, In Sun.

In: Developmental Dynamics, Vol. 230, No. 1, 01.05.2004, p. 1-11.

Research output: Contribution to journalArticle

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AU - Kim, Byeong Moo

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