ESPE Abstracts

Background: Type 1 diabetes is an autoimmune disease initiated by the invasion of pancreatic islets by immune cells that selectively kill the β cells. The loss of beta cells in Type I diabetes ultimately leads to insulin dependence and major complications that are difficult to manage by insulin injections. Regulation of immune response is a key strategy to control the autoimmunity in diabetic patients. Mesenchymal stem cells have been shown to have an apparent potential in modulating the immune reactions. However, treatment with stem cells is combined with concerns about safety issues. To overcome these concerns, in this study, we investigated the regenerative potential of exosomes isolated from wharton jelly derived mesenchymal stem cells(WJ-MSCs) to restore the β-cell mass and insulin secretion in type 1 diabetes.

Methods: WJ-MSCs exos were isolated, and dynamic light scattering, scanning electron microscopy, and transmission electron microscopy were used to analyze their physical properties. The MTS test and migration assay were used to investigate the effect of WJ-MSCs exosomes on cell proliferation and migration, and the quantitative polymerase chain reaction (qPCR) was done to assess regeneration of pancreatic beta cells by measuring insulin, Pdx1, Smad2, Smad3 and TGFβ genes. Additionally, immune-histochemical examinations were done to confirm beta cell regeneration.

Results: According to the results of the cell viability assay, the nontoxic concentration of WJ-MSCs Exos (100 µg/ml) was chosen for the subsequent investigations. The qPCR results indicated that WJ-MSCs exosomes significantly reduced the expression of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in beta cells. Regarding the assessed genes (insulin, Pdx1, Smad2, Smad3 and Tgfβ) gene expression in WJ-MSCs exosomes treated group showed significant increase compared to control group (p value < 0.001).

Conclusion: Our results suggest that WJ-MSCs exosomes improved β-cell function and regulate the insulin secretion. It may provide some useful insights into the future treatment modalities for antidiabetic purposes.