Immunomodulatory and protective effects of adipose tissue-derived mesenchymal stem cells in an allograft islet composite transplantation for experimental autoimmune type 1 diabetes

Immunol Lett. 2017 Aug;188:21-31. doi: 10.1016/j.imlet.2017.05.006. Epub 2017 May 12.

Abstract

Background: Allogeneic islet transplantation could be an ideal alternative therapy for Type 1 Diabetes Mellitus (T1DM). Adipose Tissue-derived Mesenchymal Stem Cells (AT-MSCs) characterized by immunomodulatory and protective effects may have the potential to improve the outcome of this highly immunogenic transplant.

Methods: Syngenic AT-MSCs along with allograft islets embedded in hydrogelic composite and transplanted intraperitoneally in Streptozotocin (STZ) induced diabetic C57BL/6 mice.

Results: In vitro experiments of co-imbedded islets and AT-MSCs in a hydrogel revealed AT-MSCs are able to significantly increase insulin secretion. During a 32 days of post-transplant period, blood glucose monitoring showed a decrease from over 400mg/dl to less than 150mg/dl and at the end of 32 days, mice have been dissected and assessed. Graft histopathology demonstrated that hydrogel makes an artificial immune isolation site and AT-MSCs contribute greatly to the reduction of the immune cells infiltration. Analyses of mononuclear cells isolated from Mesenteric Lymph Nodes (MLNs) and spleen showed that AT-MSCs co-transplanted with allograft decreased pro-inflammatory cytokines and increased regulatory cytokines (for both MLNs and spleen) and regulatory T cells (Treg) population (only for MLNs). In addition, real time-PCR assays revealed that transcript levels of IDO, iNOS, and PDX1, significantly increased in allograft islets in the presence of AT-MSCs.

Conclusions: according to results, this investigation indicates that AT-MSCs can be regarded as promising complementary candidates for engineered-cell therapy using hydrogel composites in islet transplantation.

Keywords: Allograft islet transplantation; Immunomodulatory and protective effects; Mesenchymal stem cells; Type 1 diabetes mellitus.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Blood Glucose
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / therapy
  • Female
  • Immunomodulation*
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Islets of Langerhans Transplantation* / methods
  • Leukocytes / immunology
  • Leukocytes / pathology
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Transplantation, Homologous

Substances

  • Blood Glucose
  • Cytokines
  • Insulin