Liraglutide Enhances the Efficacy of Human Mesenchymal Stem Cells in Preserving Islet β-cell Function in Severe Non-obese Diabetic Mice.

Glucagon-like peptide 1 (GLP-1) can promote islet β-cell replication and function, and mesenchymal stem cells (MSCs) can inhibit T cell autoimmunity. This study aimed at testing the dynamic distribution of infused human MSCs and therapeutic effect of combined MSCs and Liraglutide, a long-acting GLP-1 analogue, on preserving β-cell function in severe non-obese diabetic (NOD) mice. We found that infused MSCs accumulated in the pancreas at 4 weeks post infusion, which was not affected by Liraglutide treatment. Liraglutide significantly enhanced the function of MSCs to preserve islet β-cells by reducing glucose level at 30 minutes post glucose challenge and increasing the contents and secretion of insulin by islet β-cells in severe diabetic NOD mice. Infusion with MSCs significantly reduced insulitis scores, but increased the frequency of splenic Tregs, accompanied by reducing the levels of plasma IFN-γ and TNF-α and elevating the levels of plasma IL-10 and transforming growth factor-β1 (TGF-β1) in NOD mice. Although Liraglutide mitigated MSC-mediated changes in the frequency of Tregs and the levels of plasma IL-10, Liraglutide significantly increased the levels of plasma TGF-β1 in severe diabetic NOD mice. Therefore, our findings suggest that Liraglutide may enhance the therapeutic efficacy of MSCs in treatment of severe type 1 diabetes.