title: Disease-specific, neurosphere-derived cells as models for brain disorders.
abstract: There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery.
authors.affiliation: National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, QLD 4111, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Matigian
authors.forename: Greger
authors.initials: G
authors.lastname: Abrahamsen
authors.forename: Ratneswary
authors.initials: R
authors.lastname: Sutharsan
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Cook
authors.forename: Alejandra M
authors.initials: AM
authors.lastname: Vitale
authors.forename: Amanda
authors.initials: A
authors.lastname: Nouwens
authors.forename: Bernadette
authors.initials: B
authors.lastname: Bellette
authors.forename: Jiyuan
authors.initials: J
authors.lastname: An
authors.forename: Matthew
authors.initials: M
authors.lastname: Anderson
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Beckhouse
authors.forename: Maikel
authors.initials: M
authors.lastname: Bennebroek
authors.forename: Rowena
authors.initials: R
authors.lastname: Cecil
authors.forename: Alistair M
authors.initials: AM
authors.lastname: Chalk
authors.forename: Julie
authors.initials: J
authors.lastname: Cochrane
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Fan
authors.forename: François
authors.initials: F
authors.lastname: Féron
authors.forename: Richard
authors.initials: R
authors.lastname: McCurdy
authors.forename: John J
authors.initials: JJ
authors.lastname: McGrath
authors.forename: Wayne
authors.initials: W
authors.lastname: Murrell
authors.forename: Chris
authors.initials: C
authors.lastname: Perry
authors.forename: Jyothy
authors.initials: J
authors.lastname: Raju
authors.forename: Sugandha
authors.initials: S
authors.lastname: Ravishankar
authors.forename: Peter A
authors.initials: PA
authors.lastname: Silburn
authors.forename: Greg T
authors.initials: GT
authors.lastname: Sutherland
authors.forename: Stephen
authors.initials: S
authors.lastname: Mahler
authors.forename: George D
authors.initials: GD
authors.lastname: Mellick
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Wood
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Sue
authors.forename: Christine A
authors.initials: CA
authors.lastname: Wells
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay-Sim
mesh_terms: D001927:Brain Diseases / Q000235:genetics / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation; D048430:Cell Shape; D006801:Humans; D016130:Immunophenotyping; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009831:Olfactory Mucosa / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics