title: Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology.
abstract: 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.
authors.affiliation: Hayley Lab, Department of Neuroscience, Carleton University Ottawa, ON, Canada.
authors.forename: Gele
authors.initials: G
authors.lastname: Liu
authors.affiliation: Hayley Lab, Department of Neuroscience, Carleton University Ottawa, ON, Canada.
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rustom
authors.affiliation: Hayley Lab, Department of Neuroscience, Carleton University Ottawa, ON, Canada.
authors.forename: Darcy
authors.initials: D
authors.lastname: Litteljohn
authors.affiliation: Hayley Lab, Department of Neuroscience, Carleton University Ottawa, ON, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bobyn
authors.affiliation: Hayley Lab, Department of Neuroscience, Carleton University Ottawa, ON, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Rudyk
authors.affiliation: Hayley Lab, Department of Neuroscience, Carleton University Ottawa, ON, Canada.
authors.forename: Hymie
authors.initials: H
authors.lastname: Anisman
authors.affiliation: Hayley Lab, Department of Neuroscience, Carleton University Ottawa, ON, Canada.
authors.forename: Shawn
authors.initials: S
authors.lastname: Hayley
keywords: BDNF; depression; neurogenesis; stem cell; stress