Anti-Diabetic Therapeutic Efficacy of Mesenchymal Stem Cells-Derived from Exosomes in Rats

Background and Objective: Diabetes Mellitus (DM) type 1 is characterized by a loss of beta cells; its current therapy depends on the administration of insulin with no available curable therapy till now. We evaluated the effect of Mesenchymal Stem Cells-Derived Exosomes (MSCs-Exs) in the treatment of induced-type I DM in rats; additionally, were compared the effects of the MSCs-Exs versus the undifferentiated MSCs (Un- MSCs) and Vitamin d (Vit. D). Materials and Methods: Seventy-five rats, six weeks old, weighing 150-170 gm were equally divided into five groups, fifteen rats each: group1: healthy control group, group II: diabetic non-treated group, group III: Un-MSCs treated group, group IV: MSCs-Exs treated group and group V: Vit. D treated group. Diabetes was induced by streptozotocin (STZ) injection intraperitoneal (IP) in groups II, III, IV and V. Estimation of serum insulin and glucose levels were done after one, two and three months. At the end of the experiment, animals were sacrificed and pancreatic tissues were obtained for insulin, Smad2, Smad3, Pancreatic And Duodenal Homeobox 1 (PDX1), Paired Box 4 (PAX4) and neuro D genes expression and histopathological examinations. Results: Un-MSCs, Vit. D or MSCs-Exs resulted in lower serum glucose and higher serum insulin with significantly higher Insulin, Smad2, Smad3, PDX1, PAX4 and neuro D gene expressions compared to the diabetic non-treated group. Results were superior in the case of MSCs-Exs compared to either Un-MSCs or Vit. D. Conclusion: MSCs-Exs are found to be better than Un-MSCs or Vit. D in the treatment of experimental type-I DM. MSCs-derived exosomes may represent a novel cell-based treatment agents of type-1 DM treatment.