| Module Leader |
Professor Alan Mackay-Sim |
| Host Organisation |
National Centre for Adult Stem Cell Research, Griffith University
|
Module description
Most brain disorders and diseases arise from complex interactions
between multiple genes and multiple environmental risk factors. Stem
cells may provide useful cellular models to dissect out the cellular
and molecular causes of brain diseases but up to now, iPS cells have
been derived mostly from persons with diseases caused by single gene
mutations that have large cellular effects with less influence of
environmental risk factors. In comparison, the cellular effects of
complex diseases may be much more subtle, depending on the interplay of
many genes acting in gene networks and metabolic pathways.
This module investigates iPS cells generated from skin fibroblasts from
people with schizophrenia, a complex brain disease with strong genetic
and environmental risks but no known gene mutations. Previous
experiments demonstrate that skin fibroblasts from patients with
schizophrenia do not demonstrate disease related differences in gene
expression. The first question is whether iPS reprogramming of these
skin fibroblasts will reveal disease related information which was not
present beforehand. The second question is whether differentiating the
iPS cells into neurons is required to reveal disease related
information. iPS cell lines from multiple patients and controls will be
compared for their gene expression to investigate variability due to
individual donor and disease status.
Module Leader biography
Professor
Alan Mackay-Sim is Director of the National Centre for Adult Stem Cell
Research. The Centre investigates adult stem cells from the organ of
smell in the nose, which regenerates its sensory neurons throughout
life. Professor Mackay-Sim was scientific director of a clinical trial
where olfactory ensheathing cells were taken from the nose of people
with paraplegia and transplanted into their own injured spinal cord.
This trial provides a precedent for future trials using adult stem
cells.
Professor Mackay-Sim and his team identified a stem cell in olfactory
mucosa that is pluripotent, capable of making all cells of the body.
They showed these cells were therapeutic when transplanted into the
brain of the rat model of Parkinson’s disease. They are using olfactory
stem cells as cellular models of brain diseases and have demonstrated
key alterations in gene and protein expression and cell function in
schizophrenia and Parkinson’s disease.
Contact details
Selected publications
- Mackay-Sim A, Kittel P (1991) Cell dynamics in the adult
mouse olfactory epithelium: a quantitative autoradiographic study.
Journal of Neuroscience. 11:979-984.
- Mackay-Sim A, Kittel P (1991) On the life span of olfactory receptor neurones. European Journal of Neuroscience. 3:209-215.
- Féron
F, Perry C, McGrath JJ, Mackay-Sim A (1998) New techniques for biopsy
and culture of human olfactory epithelial neurons. Archives of
Otolaryngology Head and Neck Surgery 124:861-866.
- Newman M, Féron F and Mackay-Sim A (2000) Growth factor control of olfactory neurogenesis. Neuroscience 99:343-350.
- Newman
M, Féron F and Mackay-Sim A (2000) Growth factor regulation of
neurogenesis in adult olfactory epithelium. Neuroscience 99:343-350.
- Lu
J, Féron F, Ho SM, Mackay-Sim A and Waite PME (2001) Transplantation of
nasal olfactory tissue promotes partial recovery in paraplegic adult
rats. Brain Research 889:344-357.
- Lu J, Féron F,
Mackay-Sim A and Waite PME (2002) Olfactory ensheathing cells promote
locomotor recovery after delayed transplantation into transected spinal
cord. Brain 125: 14-21.
- Murrell W, Wetzig A, Donnellan
M, Féron F, Burne TH, Meedeniya ACB, Kesby J, Bianco J, Perry C,
Silburn PA, Mackay-Sim A (2008) Olfactory mucosa is potential source
for autologous stem cell therapy for Parkinson's disease. Stem Cells
26:2183-2192.
- Féron F, Perry C, Cochrane J, Licina P,
Nowitzke A, Uquhart S, Geraghty T, Mackay-Sim A (2005) Autologous
olfactory ensheathing cell transplantation in human spinal cord injury.
Brain 128:2951-2960.
- Mackay-Sim A, Féron F, Cochrane J,
Bassingthwaighte L, Bayliss C, Davies, W, Fronek P, Gray C, Kerr G,
Licina P, Nowitzke A, Perry C, Silburn PAS, Urquhart S and Geraghty T
(2008) Autologous olfactory ensheathing cell transplantation in human
paraplegia: a 3 year clinical trial. Brain 131:2376-2386