title: Generation and transplantation of reprogrammed human neurons in the brain using 3D microtopographic scaffolds.
abstract: Cell replacement therapy with human pluripotent stem cell-derived neurons has the potential to ameliorate neurodegenerative dysfunction and central nervous system injuries, but reprogrammed neurons are dissociated and spatially disorganized during transplantation, rendering poor cell survival, functionality and engraftment in vivo. Here, we present the design of three-dimensional (3D) microtopographic scaffolds, using tunable electrospun microfibrous polymeric substrates that promote in situ stem cell neuronal reprogramming, neural network establishment and support neuronal engraftment into the brain. Scaffold-supported, reprogrammed neuronal networks were successfully grafted into organotypic hippocampal brain slices, showing an ∼ 3.5-fold improvement in neurite outgrowth and increased action potential firing relative to injected isolated cells. Transplantation of scaffold-supported neuronal networks into mouse brain striatum improved survival ∼ 38-fold at the injection site relative to injected isolated cells, and allowed delivery of multiple neuronal subtypes. Thus, 3D microscale biomaterials represent a promising platform for the transplantation of therapeutic human neurons with broad neuro-regenerative relevance.
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, New Jersey 08854, USA.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Carlson
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, New Jersey 08854, USA.
authors.forename: Neal K
authors.initials: NK
authors.lastname: Bennett
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, New Jersey 08854, USA.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Francis
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, 89 French Street, New Brunswick, New Jersey 08854, USA.|Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, New Brunswick, New Jersey 08854, USA.
authors.forename: Apoorva
authors.initials: A
authors.lastname: Halikere
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, New Jersey 08854, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Clarke
authors.affiliation: Human Genetics Institute of New Jersey, 145 Bevier Road, Piscataway, New Jersey 08854, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Moore
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, New Jersey 08854, USA.|Human Genetics Institute of New Jersey, 145 Bevier Road, Piscataway, New Jersey 08854, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Hart
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, New Jersey 08854, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Paradiso
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Marius
authors.initials: M
authors.lastname: Wernig
authors.affiliation: Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, 145 Bevier Road, Piscataway, New Jersey 08854, USA.
authors.forename: Joachim
authors.initials: J
authors.lastname: Kohn
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, 89 French Street, New Brunswick, New Jersey 08854, USA.|Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, New Brunswick, New Jersey 08854, USA.
authors.forename: Zhiping P
authors.identifier: http://orcid.org/0000-0002-6183-1233
authors.initials: ZP
authors.lastname: Pang
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, New Jersey 08854, USA.|Department of Chemical and Biochemical Engineering, Rutgers University, 98 Brett Road, Piscataway, New Jersey 08854, USA.
authors.forename: Prabhas V
authors.initials: PV
authors.lastname: Moghe
mesh_terms: D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D065150:Cellular Reprogramming; D006801:Humans; D021621:Imaging, Three-Dimensional; D009474:Neurons / Q000166:cytology* / Q000637:transplantation*; D011108:Polymers / Q000737:chemistry; D054457:Tissue Scaffolds / Q000737:chemistry*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D011108:Polymers; D014157:Transcription Factors