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Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology
Combined cell and gene-based therapeutic strategies offer potential in the treatment of neurodegenerative and psychiatric conditions that have been associated with structural brain disturbances. In the present investigation, we used a novel virus-free re-programming method to generate induced plurip...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196567/ https://www.ncbi.nlm.nih.gov/pubmed/25352778 http://dx.doi.org/10.3389/fncel.2014.00316 |
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author | Liu, Gele Rustom, Nazneen Litteljohn, Darcy Bobyn, Jessica Rudyk, Chris Anisman, Hymie Hayley, Shawn |
author_facet | Liu, Gele Rustom, Nazneen Litteljohn, Darcy Bobyn, Jessica Rudyk, Chris Anisman, Hymie Hayley, Shawn |
author_sort | Liu, Gele |
collection | PubMed |
description | Combined cell and gene-based therapeutic strategies offer potential in the treatment of neurodegenerative and psychiatric conditions that have been associated with structural brain disturbances. In the present investigation, we used a novel virus-free re-programming method to generate induced pluripotent stem cells (iPSCs), and then subsequently transformed these cells into neural cells which over-expressed brain derived neurotrophic factor (BDNF). Importantly, the infusion of iPSC derived neural cells (as a cell replacement and gene delivery tool) and BDNF (as a protective factor) influenced neuronal outcomes. Specifically, intracerebroventricular transplantation of iPSC-derived neural progenitors that over-expressed BDNF reversed the impact of immune (lipopolysaccharide) and chronic stressor challenges upon subventricular zone adult neurogenesis, and the iPSC-derived neural progenitor cells alone blunted the stressor-induced corticosterone response. Moreover, our findings indicate that mature dopamine producing neurons can be generated using iPSC procedures and appear to be viable when infused in vivo. Taken together, these data could have important implications for using gene-plus-cell replacement methods to modulate stressor related pathology. |
format | Online Article Text |
id | pubmed-4196567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-41965672014-10-28 Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology Liu, Gele Rustom, Nazneen Litteljohn, Darcy Bobyn, Jessica Rudyk, Chris Anisman, Hymie Hayley, Shawn Front Cell Neurosci Neuroscience Combined cell and gene-based therapeutic strategies offer potential in the treatment of neurodegenerative and psychiatric conditions that have been associated with structural brain disturbances. In the present investigation, we used a novel virus-free re-programming method to generate induced pluripotent stem cells (iPSCs), and then subsequently transformed these cells into neural cells which over-expressed brain derived neurotrophic factor (BDNF). Importantly, the infusion of iPSC derived neural cells (as a cell replacement and gene delivery tool) and BDNF (as a protective factor) influenced neuronal outcomes. Specifically, intracerebroventricular transplantation of iPSC-derived neural progenitors that over-expressed BDNF reversed the impact of immune (lipopolysaccharide) and chronic stressor challenges upon subventricular zone adult neurogenesis, and the iPSC-derived neural progenitor cells alone blunted the stressor-induced corticosterone response. Moreover, our findings indicate that mature dopamine producing neurons can be generated using iPSC procedures and appear to be viable when infused in vivo. Taken together, these data could have important implications for using gene-plus-cell replacement methods to modulate stressor related pathology. Frontiers Media S.A. 2014-10-14 /pmc/articles/PMC4196567/ /pubmed/25352778 http://dx.doi.org/10.3389/fncel.2014.00316 Text en Copyright © 2014 Liu, Rustom, Litteljohn, Bobyn, Rudyk, Anisman and Hayley. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Liu, Gele Rustom, Nazneen Litteljohn, Darcy Bobyn, Jessica Rudyk, Chris Anisman, Hymie Hayley, Shawn Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology |
title | Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology |
title_full | Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology |
title_fullStr | Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology |
title_full_unstemmed | Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology |
title_short | Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology |
title_sort | use of induced pluripotent stem cell derived neurons engineered to express bdnf for modulation of stressor related pathology |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196567/ https://www.ncbi.nlm.nih.gov/pubmed/25352778 http://dx.doi.org/10.3389/fncel.2014.00316 |
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