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• W3026131967 abstract "Background & Aim Background Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by three core symptoms that include social interaction deficits, cognitive inflexibility, and communication disorders. They have been steadily increasing in children over the past several years, with no effective treatment. 2% of all ASD patients, are suffering from a disorder caused by a mutation in shank3 gene. Shank3 is an important synaptic protein, disruption of this gene directly leads to cognitive and motor impairments. During the recent decade, exosomes that derived from mesenchymal stem cells (MSC-exo) have been spotlighted as a promising therapeutic target for various clinical indications, including neurological disorders. Objective In order to develop treatment of adipose derived MSC-exo towards clinical trials, we preformed preclinical dose response studies, biodistribution, and intranasal vs intravenous studies. Repeated administration studies were also tested. Here we present results from three different autistic mice models. BTBR model as a multifactorial mice model of autism, and two different Shank3 mutated mice models. The first model is a complete deletion of exon 22 (22q13.3) and the second model is a specific insertion mutation of Guanine to 3680 position in the gene (insG3680) that leads to stop codon. Methods, Results & Conclusion Methods Exosomes were isolated using differential centrifugation protocol and characterized using the 2018MISEV guideline recommendations. Each animal received intranasal administration of 20ul containing 107 exosomes/ul. For intravenous administration, the same number of exosomes, were used, injected in 100ul. Results All three animal models showed significantly improvement in their ASD behavioral phenotypes following intranasal administration. The improvement seems to be dose dependent and was better achieved via intranasal vs intravenous administration. Biodistribution of MSC-exo showed accumulation in the brain within 72 hours, yet reduction of the signal was observed in the kidneys, heart and lungs. Conclusions Our data suggests that adipose derived MSC-exo, carry a therapeutic potential in ASD, via non-invasive intranasal administration in three different mice models. The intranasal administration is especially suitable for ASD pediatric target population. These data further emphasize our potential therapeutic strategy to reduce symptoms of autism in clinical trials." @default.
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• W3026131967 date "2020-05-01" @default.
• W3026131967 modified "2023-09-23" @default.
• W3026131967 title "Exosomes derived from adipose mesenchymal stem cells: a potential non-invasive intranasal treatment for autism" @default.
• W3026131967 doi "https://doi.org/10.1016/j.jcyt.2020.03.059" @default.
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