Long term beneficial effect of neurotrophic factors-secreting mesenchymal stem cells transplantation in the BTBR mouse model of autism

Nisim Perets, Hadar Segal-Gavish, Yael Gothelf, Ran Barzilay, Yael Barhum, Natalie Abramov, Stav Hertz, Darya Morozov, Michael London, Daniel Offen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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.

Original languageAmerican English
Pages (from-to)254-260
Number of pages7
JournalBehavioural Brain Research
Volume331
DOIs
StatePublished - 28 Jul 2017

Bibliographical note

Publisher Copyright:
© 2017

Keywords

  • Animal model
  • Autism spectrum disorder
  • Btbr
  • Mesenchymal stem cells
  • Neurotrophic factors
  • Regenerative therapy

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