title: Long term beneficial effect of neurotrophic factors-secreting mesenchymal stem cells transplantation in the BTBR mouse model of autism.
abstract: Autism spectrum disorders (ASD) are neurodevelopmental disabilities characterized by severe impairment in social communication skills and restricted, repetitive behaviors. We have previously shown that a single transplantation of mesenchymal stem cells (MSC) into the cerebral lateral ventricles of BTBR autistic-like mice resulted in an improvement across all diagnostic criteria of ASD. We suggested that brain-derived neurotrophic factor (BDNF), a protein which supports the survival and regeneration of neurons secreted by MSC, largely contributed to the beneficial behavioral effect. In this study, we investigated the behavioral effects of transplanted MSC induced to secrete higher amounts of neurotrophic factors (NurOwn®), on various ASD-related behavioral domains using the BTBR mouse model of ASD. We demonstrate that NurOwn®transplantation had significant advantages over MSC transplantation in terms of improving communication skills, one and six months following treatment, as compared to sham-treated BTBR mice. Furthermore, NurOwn®transplantation resulted in reduced stereotypic behavior for as long as six months post treatment, compared to the one month improvement observed in the MSC treated mice. Notably, NurOwn®treatment resulted in improved cognitive flexibility, an improvement that was not observed by MSC treatment. Both MSC and NurOwn®transplantation induced an improvement in social behavior that lasted for six months. In conclusion, the present study demonstrates that a single transplantation of MSC or NurOwn®have long-lasting benefits, while NurOwn®may be superior to MSC treatment.
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel- Aviv, 69978, Israel.
authors.forename: Nisim
authors.initials: N
authors.lastname: Perets
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel- Aviv, 69978, Israel.
authors.forename: Hadar
authors.initials: H
authors.lastname: Segal-Gavish
authors.affiliation: BrainStorm Cell Therapeutics, Kiryat Aryeh, Petach Tikva, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Gothelf
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel- Aviv, 69978, Israel; Research Unit at Geha Mental Health Center, Petach-Tikva, Israel.
authors.forename: Ran
authors.initials: R
authors.lastname: Barzilay
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel- Aviv, 69978, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Barhum
authors.affiliation: BrainStorm Cell Therapeutics, Kiryat Aryeh, Petach Tikva, Israel.
authors.forename: Natalie
authors.initials: N
authors.lastname: Abramov
authors.affiliation: Department of Neurobiology, Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
authors.forename: Stav
authors.initials: S
authors.lastname: Hertz
authors.affiliation: School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
authors.forename: Darya
authors.initials: D
authors.lastname: Morozov
authors.affiliation: Department of Neurobiology, Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: London
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel- Aviv, 69978, Israel. Electronic address: danioffen@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Offen
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000378:metabolism / Q000523:psychology*; D001522:Behavior, Animal / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009474:Neurons / Q000378:metabolism; D013239:Stereotyped Behavior / Q000502:physiology*; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: Animal model; Autism spectrum disorder; Btbr; Mesenchymal stem cells; Neurotrophic factors; Regenerative therapy