Isolation and in vitro characterization of pancreatic progenitor cells from the islets of diabetic monkey models

Int J Biochem Cell Biol. 2006;38(5-6):973-84. doi: 10.1016/j.biocel.2005.12.012. Epub 2006 Jan 6.

Abstract

Recent studies on the identification of stem/progenitor cells within adult mouse and human pancreatic islets have raised the possibility that autologous transplantation might be used in treating type 1 diabetes. However, it is not yet known whether such stem/progenitor cells are impaired in type 1 diabetic patients or diabetic animal models. The latter would also allow us to test the efficacy of autologous transplantation in large animal models prior to clinical applications. The present study aims to determine the existence of stem/progenitor cells in the islets of diabetic monkey models and to assess the proliferation and differentiation potential of such cells in vitro. Our results indicate that there are pancreatic progenitor cells in the adult pancreatic islets in both normal and type 1 diabetic monkeys. The isolated pancreatic progenitor cells can be greatly expanded in culture. Upon the removal of growth medium, these cells spontaneously form islet-like cell clusters, which could be further induced to secrete insulin by inductive factors. Furthermore, the secretion of insulin and C-peptide from the islet-like cell clusters responds to glucose and other stimuli, indicating that the differentiated cells not only resemble beta-cells but also possess the unique biological function of beta-cells. This study provides a foundation for further characterization of adult pancreatic progenitor cells and autologous transplantation using pancreatic progenitor cells in treating diabetic monkeys.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Peptide / metabolism
  • Cell Differentiation
  • Cell Separation / methods
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Disease Models, Animal*
  • Glucose / pharmacology
  • Insulin / metabolism
  • Insulin Secretion
  • Intermediate Filament Proteins / biosynthesis
  • Islets of Langerhans / cytology*
  • Macaca fascicularis
  • Male
  • Nerve Tissue Proteins / biosynthesis
  • Nestin
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / physiology

Substances

  • C-Peptide
  • Insulin
  • Intermediate Filament Proteins
  • NES protein, human
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Glucose