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

- Syngenic AT-MSCs along with allograft islets embedded in hydrogelic composite and transplanted intraperitoneally in Streptozotocin (STZ) induced diabetic C57BL/6 mice.
- AT-MSCs co-transplanted with allograft decreased pro-inflammatory cytokines and increased regulatory cytokines and regulatory T cells (Treg) population.
- Our procedure could be an optimal islet transplantation method and applicable in clinical trials. Because in this combination and co- transplantation of allograft and AT-MSCs, AT-MSCs have a maximum capability to increase the Treg population via cell-cell contacts and soluble factors.

BackgroundAllogeneic 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.MethodsSyngenic AT-MSCs along with allograft islets embedded in hydrogelic composite and transplanted intraperitoneally in Streptozotocin (STZ) induced diabetic C57BL/6 mice.ResultsIn 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 400 mg/dl to less than 150 mg/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.Conclusionsaccording 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.