R Navabi - Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran
E Hajizadeh-Saffar - Regenerative Medicine, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
M Hajinasrollah - Stem Cells and Developmental Biology, Animal Core Facility, Royan Institute for Stem Cell Biology and Technology, Tehran, Iran
Y Jenab - Tehran Heart Center, Tehran University of Medical Science, Teh-ran, Iran

Background: Type 1 diabetes (T1D) represents as an autoim-mune disease that β cells selectively destroy by immune cells and patients are dependent on exogenous insulin for blood glu-cose regulation. At the time of clinical diagnosis of T1D, 20-30 % of β cells remain in the pancreas. Modulating immune system concurrent to promoting beta cell function is one of the goals to develop innovative therapies of T1D. So, the preserva-tion of these remaining β cells is one of the best therapy goals to enhance the secretion of endogenous insulin. Mesenchymal stem cells (MSCs) have immunomodulatory properties. Among various drugs for T1D, GLP-1 agonists increase regeneration of β cells. So the current research project intends to investigate the effect of combination therapy of human bone marrow-derived MSCs (hBM-MSCs) transplantation along with administration of the GLP-1 agonist (liraglutide) in new-onset diabetic rhesus Macaque mulatta monkey.Materials and Methods: We developed a rhesus monkey model of diabetes induced via multiple low dose intravenous injection of 30 mg/kg b.w. streptozotocin. 1.5×106 hBM-MSCs/ kg b.w. were transplanted into the celiac artery through angi-ography method in two injections and also 1.8 mg/day Liraglutide was administered subcutaneously up to 8 weeks to the combination group. The animals were followed by functional, immunologic and histologic assessments.Results: Transplantation of 3×106 hBM-MSCs/kg b.w. com-bined with liraglutide daily injection, prevented hyperglycemia progression up to 10 weeks and improved body weight, hemo-globin A1c, fructosamine and beta cell function compared with the hBM-MSCs/monotherapy and the sham groups. With pro-tective effect of this combined treatment, Foxp3 T- regulatory cells markedly increased and inflammatory cytokines of IL-6 and IL-1 Beta decreased compared with the hBM-MSCs/mono-therapy and the sham groups. Also in morphological analysis of pancreatic tissue, lower inflammation and more normal islet were observed compared with the sham group.Conclusion: Our findings demonstrate that combination thera-py of hBM-MSCs+Liraglutide in rhesus monkey model of dia-betes, exhibited superior immunomodulation and regeneration properties in comparison with the hBM-MSCs/monotherapy and the sham groups.

Mesenchymal Stem Cell, Immunomodulation, GLP-1 Agonist, Regeneration, Non-Human Primate