Immunomodulatory properties of pancreatic islet-derived stem cells co-cultured with T cells: Does it contribute to the pathogenesis of type 1 diabetes?

Exp Clin Endocrinol Diabetes. 2014 Mar;122(3):179-89. doi: 10.1055/s-0034-1367004. Epub 2014 Jul 11.

Abstract

Background: Previously, we isolated stem cells from rat pancreatic islets (rPI-SCs) with similar characteristics of bone-marrow derived-mesenchymal stem cells (MSCs). We aimed to investigate the immunomodulatory effects of them on stimulated T-cells.

Methods: Following in vitro co-culturing directly and indirectly, the response of T-cells stimulated by concanavalin-A and immunosuppressive activity of rPI-SCs were evaluated by analysing in terms of cell viability, proliferation and apoptosis, cell cycle, differentiation of Treg, cytokines and some regulatory factors produced from T and SCs.

Results: Our results have firstly demonstrated that rPI-SCs like MSCs could regulate stimulated T-cell responses by altering their cell-cycle and cytokine profile, inhibiting the cell proliferation, and inducing the apoptosis and differentiation of Treg. Direct and indirect in vitro co-cultures of rPI-SCs with stimulated T-cells showed immunosuppressive effects.

Conclusion: Therefore, we are introducing a novel type of stem cell with immunomodulatory properties. On the other hand, it is questionable why PI-SCs cannot protect the insulin producing cells from attacks of autoreactive T-cells in the developing of type1 diabetes. For this purpose, further molecular researches in vitro and in vivo are needed to clarify why PI-SCs may not suppress attacks of autoreactive-immune-cells towards PIs. PI-SCs from diseased people should be compared with pancreas of healthy ones at both genomic and proteomic levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / immunology*
  • Adult Stem Cells / metabolism
  • Adult Stem Cells / pathology
  • Animals
  • Apoptosis
  • Autoimmunity*
  • Cell Communication
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Gene Expression Regulation
  • Immune Tolerance
  • Immunomodulation*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Lymphocyte Activation
  • Models, Biological*
  • Rats, Wistar
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Cytokines