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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 contain 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 concentration of 107 particals/ml). Three weeks post treatment the mice were tested for behavioral scoring and their results were compared to control saline treated and to 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 mice model of autism. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of this mouse model autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation.
Keywords
Autism Spectrum Disorder (ASD),Mesenchymal Stem Cells (MSC)
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CURRENT STATUS: Published
View the published article at Molecular Autism.
Version 3
Posted 23 Jul, 2020
No community comments so far
Editorial decision: Accept
On 20 Jul, 2020
Editor assigned
On 17 Jul, 2020
Submission checks complete
On 16 Jul, 2020
Editor invited
On 16 Jul, 2020
No comments provided
Editorial decision: Minor revision
On 07 Jul, 2020
Review #1 received
Received 05 Jul, 2020
Review #2 received
Received 04 Jul, 2020
Reviewer #2 agreed
On 22 Jun, 2020
Editor assigned
On 21 Jun, 2020
Reviewers invited
Invitations sent on 21 Jun, 2020
Reviewer #1 agreed
On 21 Jun, 2020
Submission checks complete
On 20 Jun, 2020
Editor invited
On 20 Jun, 2020
No comments provided
Editorial decision: Major revision
On 10 Apr, 2020
Review #2 received
Received 09 Apr, 2020
Review #1 received
Received 09 Apr, 2020
Reviewer #1 agreed
On 20 Mar, 2020
Reviewer #2 agreed
On 20 Mar, 2020
Reviewers invited
Invitations sent on 19 Mar, 2020
Editor invited
On 18 Mar, 2020
Editor assigned
On 18 Mar, 2020
Submission checks complete
On 11 Mar, 2020
First submitted
On 08 Mar, 2020
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Subject Areas
Cellular & Molecular Neuroscience
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A new preprint design is coming!
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See the published version of this preprint at Molecular Autism.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Molecular Autism.
Version 3
Posted 23 Jul, 2020
No community comments so far
Editorial decision: Accept
On 20 Jul, 2020
Editor assigned
On 17 Jul, 2020
Submission checks complete
On 16 Jul, 2020
Editor invited
On 16 Jul, 2020
No comments provided
Editorial decision: Minor revision
On 07 Jul, 2020
Review #1 received
Received 05 Jul, 2020
Review #2 received
Received 04 Jul, 2020
Reviewer #2 agreed
On 22 Jun, 2020
Editor assigned
On 21 Jun, 2020
Reviewers invited
Invitations sent on 21 Jun, 2020
Reviewer #1 agreed
On 21 Jun, 2020
Submission checks complete
On 20 Jun, 2020
Editor invited
On 20 Jun, 2020
No comments provided
Editorial decision: Major revision
On 10 Apr, 2020
Review #2 received
Received 09 Apr, 2020
Review #1 received
Received 09 Apr, 2020
Reviewer #1 agreed
On 20 Mar, 2020
Reviewer #2 agreed
On 20 Mar, 2020
Reviewers invited
Invitations sent on 19 Mar, 2020
Editor invited
On 18 Mar, 2020
Editor assigned
On 18 Mar, 2020
Submission checks complete
On 11 Mar, 2020
First submitted
On 08 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cellular & Molecular Neuroscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Molecular Autism.
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 contain 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 concentration of 107 particals/ml). Three weeks post treatment the mice were tested for behavioral scoring and their results were compared to control saline treated and to 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 mice model of autism. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of this mouse model autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
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