Document Detail


Disease-specific, neurosphere-derived cells as models for brain disorders.
MedLine Citation:
PMID:  20699480     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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:
Nicholas Matigian; Greger Abrahamsen; Ratneswary Sutharsan; Anthony L Cook; Alejandra M Vitale; Amanda Nouwens; Bernadette Bellette; Jiyuan An; Matthew Anderson; Anthony G Beckhouse; Maikel Bennebroek; Rowena Cecil; Alistair M Chalk; Julie Cochrane; Yongjun Fan; François Féron; Richard McCurdy; John J McGrath; Wayne Murrell; Chris Perry; Jyothy Raju; Sugandha Ravishankar; Peter A Silburn; Greg T Sutherland; Stephen Mahler; George D Mellick; Stephen A Wood; Carolyn M Sue; Christine A Wells; Alan Mackay-Sim
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-10
Journal Detail:
Title:  Disease models & mechanisms     Volume:  3     ISSN:  1754-8411     ISO Abbreviation:  Dis Model Mech     Publication Date:    2010 Nov-Dec
Date Detail:
Created Date:  2010-10-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101483332     Medline TA:  Dis Model Mech     Country:  England    
Other Details:
Languages:  eng     Pagination:  785-98     Citation Subset:  IM    
Affiliation:
National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, QLD 4111, Australia.
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