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Mol Autism. 2018 Nov 21;9:57. doi: 10.1186/s13229-018-0240-6. eCollection 2018.

Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice.

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1Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
2Edmond and Lily Safra Center for Brain Sciences, Hebrew University, Jerusalem, Israel.
3Sacklar School of Medicine, Department of Human Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel.


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. BTBR T+tf/J (BTBR) mice are an accepted model of evaluating autistic-like behaviors as they present all core symptoms of ASD. We have previously shown that transplantation of human bone marrow mesenchymal stem cells (MSC) to the lateral ventricles of BTBR mice results in long lasting improvement in their autistic behavioral phenotypes. Recent studies point exosomes as the main mediators of the therapeutic effect of MSC. Here, we tested whether treatment with the exosomes secreted from MSC (MSC-exo) will show similar beneficial effects. We found that intranasal administration of MSC-exo increased male to male social interaction and reduced repetitive behaviors. Moreover, the treatment led to increases of male to female ultrasonic vocalizations and significant improvement in maternal behaviors of pup retrieval. No negative symptoms were detected following MSC-exo intranasal treatments in BTBR or healthy C57BL mice. The marked beneficial effects of the exosomes in BTBR mice may translate to a novel, non-invasive, and therapeutic strategy to reduce the symptoms of ASD.

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Conflict of interest statement

All experimental protocols were approved by the Tel Aviv University Committee of Animal Use for Research and Education.Not applicable.DO and NP have submitted several patent applications related to exosomes. All were assigned to “Ramot at Tel Aviv University.” Brainstorm Cell Therapeutics to “Stem Cell Medicine.” The other authors have nothing to disclose.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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