Study of anti-inflammatory and immunomodulatory potential of endometrial mesenchymal stem cells-derived exosomes with micro-ultrasound (μUS) guidance in regeneration β-islets on T1D animal model

Abstract

Type 1 diabetes results from the inflammatory destruction of beta cells, leading to severe insulin deficiency. MSCs have an effective role in modulating immune and inflammatory reactions and are known as a standard platform for the treatment in regenerative medicine. Despite evidence of MScs’ effectiveness in diseases, they still are associated with safety challenges. Exosomes are natural nanoparticles secreted into the extracellular space by most cells. After the isolation and characterization of human Endometrial MSC-derived exosomes (hEnEx), diabetes model was induced by destroying islets using intraperitoneal injection of streptozotocin (STZ) in male rats. The characterized EnEx and EnMSCs were injected into pancreatic areas in diabetic animals under guidance of the micro-ultrasound non-invasive method. In the current study, the animals' blood glucose levels and body weight were monitored, accompanied by increased body weight and decreased blood sugar in the treated groups. Our findings indicate specific therapeutic effects of EnEx in β-islets neogenesis, normal islets formation, and insulin secretion. Evidence that shows functional role of EnEx in regulation of inflammatory and immune responses in EnEx-treated rats. Evaluation of insulin and pdx1 proteins expression showed presence of insulin and also EnEx antidiabetics effects in β-cells through the pdx1 pathway. This study determined that exosome therapy is more effective compared to cell therapy in improving diabetes, especially regeneration of β-islets mass. Also, exosome injection with the micro-ultrasound method has more efficacy in restoring β‐cell function. Therefore, EnEx based-treatment can be a novel therapeutic agent with minimal or no unwanted side effects for diabetic patients.