Islet-derived fibroblast-like cells are not derived via epithelial-mesenchymal transition from Pdx-1 or insulin-positive cells

Diabetes. 2007 Jan;56(1):3-7. doi: 10.2337/db06-1165. Epub 2006 Nov 16.

Abstract

As recent studies suggest that newly formed pancreatic beta-cells are a result of self-duplication rather than stem cell differentiation, in vitro expansion of beta-cells presents a potential mechanism by which to increase available donor tissue for cell-based diabetes therapies. Although most studies have found that beta-cells are resilient to substantial in vitro expansion, recent studies have suggested that it is possible to expand these cells through a process referred to as epithelial-mesenchymal transition (EMT). To further substantiate such an expansion mechanism, we used recombination-based genetic lineage tracing to determine the origin of proliferating fibroblast-like cells from cultured pancreatic islets in vitro. We demonstrate, using two culture methods, that EMT does not underlie the appearance of fibroblast-like cells in mouse islet cultures but that fibroblast-like cells appear to represent mesenchymal stem cell (MSC)-like cells akin to MSCs isolated from bone marrow.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Division
  • DNA, Complementary / genetics
  • Epithelial Cells / physiology*
  • Fibroblasts / cytology*
  • Fibroblasts / physiology*
  • Flow Cytometry
  • Homeodomain Proteins / physiology*
  • Hyaluronan Receptors / analysis
  • Insulin / physiology*
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / metabolism
  • Leukocyte Common Antigens / analysis
  • Mesoderm / cytology
  • Mesoderm / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Polymerase Chain Reaction
  • RNA / genetics
  • RNA / isolation & purification
  • Trans-Activators / physiology*

Substances

  • DNA, Complementary
  • Homeodomain Proteins
  • Hyaluronan Receptors
  • Insulin
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • RNA
  • Leukocyte Common Antigens