Razi Journal of Medical Sciences

Background: Type 1 diabetes (T1D) is a T-cell mediated autoimmune disorder in which pancreas beta-cell destruction causes insulin deficiency and hyperglycemia. In addition to daily insulin treatment, allogeneic islet transplant inT1D is another therapeutic way that needs immunosuppressive drugs to control autoimmune damage and graft rejection. Since life-long application of these drugs is associated with serious side-effects, we proposed local immunomodulatory effect of mesenchymal stem cells (MSCs). The aim of this study was to investigate in vitro inhibitory influence of adipose-derived MSCs on C57BL/6 diabetic mouse splenocytes proliferation against syngeneic islet cells lysate.

Methods: MSCs were extracted from abdominal fat tissue of healthy C57BL/6 mouse and cultured to prolipherate. Then, they were immunophynotyped and their differentiation to osteo- and adipocyte was approved. Diabetic C57BL/6 mouse model was prepared by administration of consecutive low-doses of sterptozotocin and diabetic state was confirmed by serum glucose (>300 mg/dL) and insulin levels, and pancreas histopathology. Pancreas islets were isolated from healthy mouse and splenocytes prepared from healthy and diabetic mice. To evaluate anti-proliferative effect of MSCs, they were co-cultured with splenocytes in the presence of islet lysate and proliferation was assayed by MTT technique. The presented data are mean SD and statistically analyzed with one way ANOVA.

Results: Extraction and identification (Immunolphenotyping and differentiation) of MSCs had acceptable outcome.Diabetic state was confirmedin our model (blood glucose: 300±20 vs. 95±10 Insulin level: 4.9±0.5 vs 0.3±0.1 and lack of Langerhans islets in tissue sections). The co-culture experiments demonstrated that MSCs significantly decreased diabetic splenocytes proliferation in the presence of islet cells lysate (p<0.05).

Conclusion: MSCs can effectively inhibit autoimmune response of diabetic splenocytes against islet cells lysate. Assessing MSCs immunomodulatory effects and differentiation property to insulin-producing cells may provide a new horizon for T1D treatment in the future.