ICRS 2018

Exosomes as Trojan horses for brain disorders treatment

Daniel Offen 1,2 Nisim Perets 2 Oshra Betzer 3 Stav Hertz 4 Michael London 4 Rachela Popovtzer 3
1Sacklar School of Medicine, Tel Aviv University, Tel Aviv, Israel
2Sagol School of neuroscience, Tel Aviv University, Tel Aviv, Israel
3Faculty of Engineering and the Institute of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat Gan, Israel
4Edmond and Lily Safra center for brain sciences, Hebrew University, Jerusalem, Israel

Exosomes are nano-vesicles secreted by different cell types, which enable intercellular communication of cells in their vicinity or at distant sites. Recent studies established that exosomes derived from mesenchymal stem cells (MSC-exo) carry miRNA and proteins that can promote regeneration and immunomodulation processes in damaged tissues. We developed a method for longitudinal and quantitative in vivo neuroimaging of exosomes, based on the superior visualization abilities of classical X-ray computed tomography (CT), and combined with gold nanoparticles (GNPs) as labeling agents. Using this technique, we tracked the migration and homing patterns of MSC-exo in different and common brain pathologies in mice, after intranasal delivery. Moreover, in BTBR mice, which are an accepted model of evaluating autistic-like behaviors. We found that intranasal administration of MSC-exo social interaction and reduced repetitive behaviors. Moreover, the treatment led to increases male to female ultrasonic vocalizations and significant improvement in maternal behaviors of pup retrieval. The marked beneficial effects of the exosomes in mice models may translate to a novel, non-invasive, and therapeutic strategy to reduce the symptoms in autism spectrum disorders.









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