Protection of rat pancreatic islet function and viability by coculture with rat bone marrow-derived mesenchymal stem cells

Cell Death Dis. 2010 Apr 22;1(4):e36. doi: 10.1038/cddis.2010.14.

Abstract

The maintenance of viable and functional islets is critical in successful pancreatic islet transplantation from cadaveric sources. During the isolation procedure, islets are exposed to a number of insults including ischemia, oxidative stress and cytokine injury that cause a reduction in the recovered viable islet mass. A novel approach was designed in which streptozotocin (STZ)-damaged rat pancreatic islets (rPIs) were indirectly cocultured with rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) to maintain survival of the cultured rPIs. The results indicated that islets cocultured with rBM-MSCs secreted an increased level of insulin after 14 days, whereas non-cocultured islets gradually deteriorated and cell death occurred. The cocultivation of rBM-MSCs with islets and STZ-damaged islets showed the expression of IL6 and transforming growth factor-β1 in the culture medium, besides the expression of the antiapoptotic genes (Mapkapk2, Tnip1 and Bcl3), implying the cytoprotective, anti-inflammatory and antiapoptotic effects of rBM-SCs through paracrine actions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bone Marrow Cells / cytology*
  • Cell Differentiation / drug effects
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / metabolism
  • Dithizone / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Profiling
  • Immunohistochemistry
  • Insulin / metabolism
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology*
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Rats
  • Rats, Wistar
  • Staining and Labeling
  • Streptozocin / pharmacology
  • Tissue Culture Techniques

Substances

  • Cytokines
  • Insulin
  • Streptozocin
  • Dithizone