Combined therapy of mesenchymal stem cells with a GLP-1 receptor agonist, liraglutide, on an inflammatory-mediated diabetic non-human primate model

Aims: Immunomodulation concurrent with the promotion of fi-cell function is a strategy used to develop innovative therapies for type 1 diabetes (T1D). Here, we assessed the therapeutic potential of co-administration of human clonal mesenchymal stem (stromal) cells (hBM-cMSCs) and liraglutide as a glucagon-like peptide-1 agonist in a non-human primate model with streptozotocin (STZ)-induced diabetes. Main methods: Diabetes was induced through intravenous (i.v.) multiple low-dose (MLD) infusions of STZ at a dose of 30 mg/kg body weight (b.w.) for five consecutive days, followed by two booster injections of 35 mg/kg on days 12 and 19. After 90 days, the diabetic animals were randomly allocated to two groups: The combination therapy group (n = 4) received injections of 1.5 ? 106 hBM-cMSCs/kg b.w. through celiac artery by angiography on days 91 and 105 and daily subcutaneous injections of liraglutide (up to 1.8 mg/day) until day 160 while vehicle group received phosphate-buffered saline. The monkeys were assessed for functional, immunological, and histological analysis. Key findings: The combined treatment group had continued reduction in FBG levels up to day 160, which was accompanied by increased b.w., C-peptide, and fi-cell function, and decreased HbA1c and fructosamine levels compared to vehicle group. The combined treatment increased Tregs, IL-4, IL-10, and TGF-fi1 and decreased IL-6 and IL-1fi. Stereological analysis of the pancreatic tissue exhibited more total volume of insulin-secreting islets in the combined treatment group compared to vehicle group. Significance: Our findings demonstrated this combined treatment impaired the clinical symptoms of diabetes in this animal model through immunomodulation and fi-cell preservation.