Disease-specific, neurosphere-derived cells as models for brain disorders.
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.
Matigian
Nicholas
N
National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, QLD 4111, Australia.
Abrahamsen
Greger
G
Sutharsan
Ratneswary
R
Cook
Anthony L
AL
Vitale
Alejandra M
AM
Nouwens
Amanda
A
Bellette
Bernadette
B
An
Jiyuan
J
Anderson
Matthew
M
Beckhouse
Anthony G
AG
Bennebroek
Maikel
M
Cecil
Rowena
R
Chalk
Alistair M
AM
Cochrane
Julie
J
Fan
Yongjun
Y
Féron
François
F
McCurdy
Richard
R
McGrath
John J
JJ
Murrell
Wayne
W
Perry
Chris
C
Raju
Jyothy
J
Ravishankar
Sugandha
S
Silburn
Peter A
PA
Sutherland
Greg T
GT
Mahler
Stephen
S
Mellick
George D
GD
Wood
Stephen A
SA
Sue
Carolyn M
CM
Wells
Christine A
CA
Mackay-Sim
Alan
A
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