Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mice model of autism Shank3B

Abstract

Background: Partial or an entire deletion of SHANK3 are considered as major drivers in the Phelan McDermid syndrome, in which 75% of patients are diagnosed with autism spectrum disorder (ASD). During the recent years, there was an increasing interest in stem cell therapy in ASD, and specifically, mesenchymal stem cells (MSC). Moreover, it has been suggested that the therapeutic effect of the MSC is mediated mainly via the secretion of small extracellular-vesicle that contain important molecular information of the cell and are used for cell-to cell communication. Within the fraction of the extracellular-vesicles, exosomes were highlighted as the most effective ones to convey the therapeutic effect.Methods: Exosomes derived from MSC (MSC-exo) were purified, characterized and given via intranasal administration to Shank3B KO mice (in concentration of 107 particals/ml). Three weeks post treatment the mice were tested for behavioral scoring and their results were compared to control saline treated and to their wild type littermates. Results: Intranasal treatment with MSC-exo improves the social behavior deficit in multiple paradigms, increases vocalization and reduces repetitive behaviors. We also observed an increase of GABARB1 in the prefrontal cortex.Conclusions: Herein, we hypothesized that MSC-exo would have a direct beneficial effect on the behavioral autistic-like phenotype of the genetically modified Shank3B KO mice model of autism. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of this mouse model autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation.Limitations: Although the behavioral scoring of the MSC-exo treated group was significantly improved compared to their saline treated littermates, there is much more to learn regarding the mechanism of action of the MSC-exo.