Disease-specific, neurosphere-derived cells as models for brain disorders

Matigian, N, Abrahamsen, G, Sutharsan, R, Cook, AL, Vitale, AM, Nouwens, A, Bellette, B, An, JY, Anderson, M, Beckhouse, AG, Bennebroek, M, Cecil, R, Chalk, AM, Cochrane, J, Fan, YJ, Feron, F, McCurdy, R, McGrath, JJ, Murrell, W, Perry, C, Raju, J, Ravishankar, S, Silburn, PA, Sutherland, GT, Mahler, S, Mellick, GD, Wood, SA, Sue, CM, Wells, CA and Mackay-Sim, A (2010) Disease-specific, neurosphere-derived cells as models for brain disorders. Disease Models and Mechanisms, 3 11-12: 785-798. doi:10.1242/dmm.005447

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Author Matigian, N
Abrahamsen, G
Sutharsan, R
Cook, AL
Vitale, AM
Nouwens, A
Bellette, B
An, JY
Anderson, M
Beckhouse, AG
Bennebroek, M
Cecil, R
Chalk, AM
Cochrane, J
Fan, YJ
Feron, F
McCurdy, R
McGrath, JJ
Murrell, W
Perry, C
Raju, J
Ravishankar, S
Silburn, PA
Sutherland, GT
Mahler, S
Mellick, GD
Wood, SA
Sue, CM
Wells, CA
Mackay-Sim, A
Title Disease-specific, neurosphere-derived cells as models for brain disorders
Journal name Disease Models and Mechanisms   Check publisher's open access policy
ISSN 1754-8403
Publication date 2010-11-01
Year available 2010
Sub-type Article (original research)
DOI 10.1242/dmm.005447
Open Access Status DOI
Volume 3
Issue 11-12
Start page 785
End page 798
Total pages 14
Place of publication United Kingdom
Publisher The Company of Biologists Ltd.
Language eng
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.
Keyword Sporadic parkinsons-disease
Apoe receptor 2
Adult human
Olfactory epithelium
Neurodevelopmental hypothesis
Environment interactions
Skin fibroblasts
Altered adhesion
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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Created: Sun, 05 Dec 2010, 10:14:39 EST