Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B / N. PERETS in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 65 p. Titre : Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B Type de document : Texte imprimé et/ou numérique Auteurs : N. PERETS, Auteur ; O. ORON, Auteur ; S. HERMAN, Auteur ; E. ELLIOTT, Auteur ; Daniel OFFEN, Auteur Article en page(s) : 65 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Partial or an entire deletion of SHANK3 are considered as major drivers in the Phelan-McDermid syndrome, in which 75% of patients are diagnosed with autism spectrum disorder (ASD). During the recent years, there was an increasing interest in stem cell therapy in ASD, and specifically, mesenchymal stem cells (MSC). Moreover, it has been suggested that the therapeutic effect of the MSC is mediated mainly via the secretion of small extracellular vesicle that contains important molecular information of the cell and are used for cell-to-cell communication. Within the fraction of the extracellular vesicles, exosomes were highlighted as the most effective ones to convey the therapeutic effect. METHODS: Exosomes derived from MSC (MSC-exo) were purified, characterized, and given via intranasal administration to Shank3B KO mice (in the concentration of 10(7) particles/ml). Three weeks post treatment, the mice were tested for behavioral scoring, and their results were compared with saline-treated control and their wild-type littermates. RESULTS: Intranasal treatment with MSC-exo improves the social behavior deficit in multiple paradigms, increases vocalization, and reduces repetitive behaviors. We also observed an increase of GABARB1 in the prefrontal cortex. CONCLUSIONS: Herein, we hypothesized that MSC-exo would have a direct beneficial effect on the behavioral autistic-like phenotype of the genetically modified Shank3B KO mouse model of autism. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of this mouse model of autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation. En ligne : http://dx.doi.org/10.1186/s13229-020-00366-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433 [article] Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B [Texte imprimé et/ou numérique] / N. PERETS, Auteur ; O. ORON, Auteur ; S. HERMAN, Auteur ; E. ELLIOTT, Auteur ; Daniel OFFEN, Auteur . - 65 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 65 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Partial or an entire deletion of SHANK3 are considered as major drivers in the Phelan-McDermid syndrome, in which 75% of patients are diagnosed with autism spectrum disorder (ASD). During the recent years, there was an increasing interest in stem cell therapy in ASD, and specifically, mesenchymal stem cells (MSC). Moreover, it has been suggested that the therapeutic effect of the MSC is mediated mainly via the secretion of small extracellular vesicle that contains important molecular information of the cell and are used for cell-to-cell communication. Within the fraction of the extracellular vesicles, exosomes were highlighted as the most effective ones to convey the therapeutic effect. METHODS: Exosomes derived from MSC (MSC-exo) were purified, characterized, and given via intranasal administration to Shank3B KO mice (in the concentration of 10(7) particles/ml). Three weeks post treatment, the mice were tested for behavioral scoring, and their results were compared with saline-treated control and their wild-type littermates. RESULTS: Intranasal treatment with MSC-exo improves the social behavior deficit in multiple paradigms, increases vocalization, and reduces repetitive behaviors. We also observed an increase of GABARB1 in the prefrontal cortex. CONCLUSIONS: Herein, we hypothesized that MSC-exo would have a direct beneficial effect on the behavioral autistic-like phenotype of the genetically modified Shank3B KO mouse model of autism. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of this mouse model of autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation. En ligne : http://dx.doi.org/10.1186/s13229-020-00366-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433

Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice / N. PERETS in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 57p. Titre : Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice Type de document : Texte imprimé et/ou numérique Auteurs : N. PERETS, Auteur ; S. HERTZ, Auteur ; M. LONDON, Auteur ; Daniel OFFEN, Auteur Article en page(s) : 57p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : 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. En ligne : https://dx.doi.org/10.1186/s13229-018-0240-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice [Texte imprimé et/ou numérique] / N. PERETS, Auteur ; S. HERTZ, Auteur ; M. LONDON, Auteur ; Daniel OFFEN, Auteur . - 57p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 57p. Index. décimale : PER Périodiques Résumé : 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. En ligne : https://dx.doi.org/10.1186/s13229-018-0240-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

Mesenchymal Stem Cell Transplantation Promotes Neurogenesis and Ameliorates Autism Related Behaviors in BTBR Mice / Hadar SEGAL-GAVISH in Autism Research, 9-1 (January 2016)  

Public ISBD [article]  inAutism Research > 9-1 (January 2016) . - p.17-32 Titre : Mesenchymal Stem Cell Transplantation Promotes Neurogenesis and Ameliorates Autism Related Behaviors in BTBR Mice Type de document : Texte imprimé et/ou numérique Auteurs : Hadar SEGAL-GAVISH, Auteur ; Golan KARVAT, Auteur ; Noy BARAK, Auteur ; Ran BARZILAY, Auteur ; Javier GANZ, Auteur ; Liat EDRY, Auteur ; Israel AHARONY, Auteur ; Daniel OFFEN, Auteur ; Tali KIMCHI, Auteur Article en page(s) : p.17-32 Langues : Anglais (eng) Mots-clés : BTBR  animal model  MSC  BDNF  neurogenesis Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are characterized by social communication deficits, cognitive rigidity, and repetitive stereotyped behaviors. Mesenchymal stem cells (MSC) have a paracrine regenerative effect, and were speculated to be a potential therapy for ASD. The BTBR inbred mouse strain is a commonly used model of ASD as it demonstrates robust behavioral deficits consistent with the diagnostic criteria for ASD. BTBR mice also exhibit decreased brain-derived neurotrophic factor (BDNF) signaling and reduced hippocampal neurogenesis. In the current study, we evaluated the behavioral and molecular effects of intracerebroventricular MSC transplantation in BTBR mice. Transplantation of MSC resulted in a reduction of stereotypical behaviors, a decrease in cognitive rigidity and an improvement in social behavior. Tissue analysis revealed elevated BDNF protein levels in the hippocampus accompanied by increased hippocampal neurogenesis in the MSC-transplanted mice compared with sham treated mice. This might indicate a possible mechanism underpinning the behavioral improvement. Our study suggests a novel therapeutic approach which may be translatable to ASD patients in the future. En ligne : http://dx.doi.org/10.1002/aur.1530 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282 [article] Mesenchymal Stem Cell Transplantation Promotes Neurogenesis and Ameliorates Autism Related Behaviors in BTBR Mice [Texte imprimé et/ou numérique] / Hadar SEGAL-GAVISH, Auteur ; Golan KARVAT, Auteur ; Noy BARAK, Auteur ; Ran BARZILAY, Auteur ; Javier GANZ, Auteur ; Liat EDRY, Auteur ; Israel AHARONY, Auteur ; Daniel OFFEN, Auteur ; Tali KIMCHI, Auteur . - p.17-32. Langues : Anglais (eng) in Autism Research > 9-1 (January 2016) . - p.17-32 Mots-clés : BTBR  animal model  MSC  BDNF  neurogenesis Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are characterized by social communication deficits, cognitive rigidity, and repetitive stereotyped behaviors. Mesenchymal stem cells (MSC) have a paracrine regenerative effect, and were speculated to be a potential therapy for ASD. The BTBR inbred mouse strain is a commonly used model of ASD as it demonstrates robust behavioral deficits consistent with the diagnostic criteria for ASD. BTBR mice also exhibit decreased brain-derived neurotrophic factor (BDNF) signaling and reduced hippocampal neurogenesis. In the current study, we evaluated the behavioral and molecular effects of intracerebroventricular MSC transplantation in BTBR mice. Transplantation of MSC resulted in a reduction of stereotypical behaviors, a decrease in cognitive rigidity and an improvement in social behavior. Tissue analysis revealed elevated BDNF protein levels in the hippocampus accompanied by increased hippocampal neurogenesis in the MSC-transplanted mice compared with sham treated mice. This might indicate a possible mechanism underpinning the behavioral improvement. Our study suggests a novel therapeutic approach which may be translatable to ASD patients in the future. En ligne : http://dx.doi.org/10.1002/aur.1530 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282

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