title: In vivo modeling of neuronal function, axonal impairment and connectivity in neurodegenerative and neuropsychiatric disorders using induced pluripotent stem cells.
abstract: Modeling neurological diseases using human embryonic or patient-derived induced pluripotent stem cells (iPSCs) improves the understanding of molecular and cellular changes underlying these diseases and can lead to new, potentially personalized therapies. Changes in expression of axon guidance cues and altered cytoskeletal maintenance have been implicated in neurodegenerative and neuropsychiatric disorders. To date, most of the iPSC patient-derived cellular dysfunction and phenotypic studies have been performed in vitro. To study the intrinsic axonal impairments and neuronal connectivity deficits in human disease iPSC-derived neurons we propose to graft these cells into the physiological three-dimensional multi-structural environment of the central nervous system of rodent models to obtain relevant in vivo data. Such human iPSC in vivo chimeric models can allow for neuronal maturation, capture neuropathological phenotypes of axonal and connectivity impairments, and serve as target engagement and drug validation studies using human cells, thus highly relevant for advancement of the drug development process in the late pre-clinical stages.
authors.affiliation: Neuroregeneration Research Institute, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA; Harvard Medical School, USA. Electronic address: jkorecka@mclean.harvard.edu.
authors.forename: J A
authors.initials: JA
authors.lastname: Korecka
authors.affiliation: Neuroregeneration Research Institute, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA; Harvard Medical School, USA.
authors.forename: S
authors.initials: S
authors.lastname: Levy
authors.affiliation: Neuroregeneration Research Institute, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA; Harvard Medical School, USA. Electronic address: isacson@hms.harvard.edu.
authors.forename: O
authors.initials: O
authors.lastname: Isacson
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D001523:Mental Disorders / Q000628:therapy*; D009416:Nerve Regeneration; D019636:Neurodegenerative Diseases / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*
keywords: Neurodegenerative and neuropsychiatric diseases; iPSC models