Exosomes Isolated from Menstrual Blood-Derived Mesenchymal Stem Cells Regenerate the Beta Cell Mass in Diabetic Type 1 Animal Model

Background and Aim: Diabetes type 1 is characterized by the lack ofinsulin production as a result of degeneration of insulin-producingbeta cells in the pancreas. The autoimmune response against beta cellsis the main reason for this disease; therefore, any strategies that helpimmune response regulation can be beneficial. Studies have shown theeffectiveness of mesenchymal stem cells (MSCs) in the regulation of Tcell response and pancreatic islet repair. However, the application ofMSCs accompanies the cell therapy safety issue. The unknown fate ofinjected stem cells is one of the major safety concerns regarding stem celltherapies; therefore, in this study, we have used the exosomal secretomeof MSCs to regenerate insulin-producing cellsMethods: MSCs were isolated from menstrual blood as a rich andnoninvasive source of MSCs. Exosomes were isolated and characterizedusing western blot and AFM, SEM techniques. Exosomes were injectedintravenously at different time points after induction of diabetes usingSTZ. Blood glucose and insulin levels were measured at pre-determinedtime points and animals were sacrificed at day 60 and regenerationof beta cells and insulin production at pancreas were analyzed usingimmunohistochemistry.Results: Flow cytometric and differentiation assays confirmed thecharacters of MSCs derived from menstrual blood. The presence ofCD81, CD63, Tsg-101, Calnexin markers on exosomes was confirmedusing western blotting and AFM and SEM analysis verified the presenceof purified exosomes. Altogether, the blood levels of glucose and insulin and the histochemistry analyses represented the regenerative potential ofexosomes isolated from menstrual blood-derived MSCs in the restorationof insulin-producing cells. The in vivo tracking of exosomes furtherconfirmed the involvement of exosomes in beta cell regenerationConclusion: Although very successful in preclinical studies,mesenchymal stem cells have still very limited therapeutic applicationsin clinics mainly because of its safety concerns. Secreted exosome fromthese cells exerts the most beneficial properties of stem cells; however,they follow fewer safety issues as they are not active agents as cells are.This work represents the effectiveness of MSC-derived exosomes in theregeneration of pancreatic beta cells.

کلیدواژه ها:

Stem cell ، Exosome ، Diabetes type regeneration beta cell