ADMSC Exo‐MicroRNA‐22 improve neurological function and neuroinflammation in mice with Alzheimer's disease

Abstract The previous study by our group has found that miRNA‐22 can inhibit pyroptosis by targeting GSDMD and improve the memory and motor ability of mice with Alzheimer's disease (AD) mice by inhibiting inflammatory response. In recent years, stem cells and their exosomes have been reported to have good therapeutic effects on AD; therefore, we hypothesize that miRNA‐22 is likely to play a synergistic therapeutic effect. In this study, adipose‐derived mesenchymal stem cells (ADMSCs) were transfected into miRNA‐22 mimic to obtain miRNA‐22 loaded exosomes (Exo‐miRNA‐22), which was further used for the treatment and nerve repair of AD. In brief, 4‐month‐old APP/PS1 mice were assigned into the control group, Exo and Exo‐miRNA‐22 groups. After exosome transplantation, we observed changes in the motor and memory ability of mice. In addition, ELISA was used to detect the expression of inflammatory factors in cerebrospinal fluid and peripheral blood, Nissl staining was used to assess the survival of mouse nerve cells, immunofluorescence staining was used to determine the activation of microglia, and Western blot was utilized to detect the expression of pyroptosis‐related proteins. As a result, the nerve function and motor ability were significantly higher in mice in the Exo‐miRNA‐22 group than those in the control group and Exo group. Meanwhile, the survival level of nerve cells in mice was higher in the Exo‐miRNA‐22 group, and the expression of inflammatory factors was lower than that of the Exo group, indicating Exo‐miRNA‐22 could significantly suppress neuroinflammation. In vitro culture of PC12 cells, Aβ 25‐35 ‐induced cell damage, detection of PC12 apoptotic level, the release of inflammatory factors and the expression of pyroptosis‐related proteins showed that Exo‐miRNA‐22 could inhibit PC12 apoptosis and significantly decrease the release of inflammatory factors. In this study, we found that miRNA‐22‐loaded ADMSC‐derived exosomes could decrease the release of inflammatory factors by inhibiting pyroptosis, thereby playing a synergetic therapeutic role with exosomes on AD, which is of great significance in AD research.