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

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.

Researchers at Tel Aviv University 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, the researchers tested whether treatment with the exosomes secreted from MSC (MSC-exo) will show similar beneficial effects. They 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.

Comparison between MSC-exo and MSC labeled with PKH26 visualization in the brain

exosomes

a From left to right: MSC-exo intranasal, MSC-exo intravenous, MSC intranasal, and MSC intravenous. MSC-exo cross the blood brain barrier, both intranasally and intravenously, while MSC much less. b Immunostaining of neurons, DAPI and PKH26 labeled MSC-exo after intranasal administration. c Sagittal section of the BTBR MSC-exo brain after intranasal administration of PKH26 labeled MSC-exo (top) and Alan brain atlas (bottom)

Perets N, Hertz S, London M, Offen D. (2018) Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice. Mol Autism 9:57. [article]

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