Research Programs
1. Developing a skin-to-neuron autologous adult stem cell technology for Alzheimer’s disease
1.1 Skin-derived neuroprogenitor model
Skin-derived neuroprogenitors could be an important source of autologous cells for transplantation in various neurodegenerative diseases. We have previously optimized a two-stage protocol to generate large numbers of neuroprecursors from adult dog and human fetal skin that typically exhibit neuronal characteristics in vitro using gene and protein expression analyses. Our interest in canine stem cells have expanded from skin-based tissue sources to brain-derived stem cells. For the first time, we isolated neurospheres from different adult canine brain regions after post mortem dissection, successfully passaged cells in suspension culture, and then differentiated these into neural-like and glial-like cells. We are also evaluating the potential of both iPSC- and SKiNP–based systems as cellular in vitro models for Alzheimer’s disease by generating neurons from adult canine SKiNPs to an efficient, high–yield adult human protocol and comparing this with human iPSC using electrophysiological and synaptic analyses.
Investigators: Aileen Lowe, Ariel Seaton, Michael Valenzuela, Perminder Sachdev, and Kuldip Sidhu
1.2 Effects of physical exercise and neuroprogenitor transplantation in the reversal of age-related memory impairment
There is a potential role for neurogenesis in restoring neuronal and synaptic loss, major pathological features of many disorders associated with ageing, including Alzheimer's disease. Voluntary motor activity may constitute one of the triggers for neurogenesis. This study aims to identify the most sensitive behavioural measure of age-associated cognitive performance in rodents as well as assessing whether voluntary wheel running can reduce the adverse effects of ageing on cognitive performance.
Investigators: Joyce Siette, Michael Valenzuela, Fred Westbrook, Kuldip Sidhu and Perminder Sachdev
2. Developing a stem cell therapy for Parkinson’s disease
2.1 hESC as a potential source of dopaminergic neurons
The major theme of this project is to generate pan dopaminergic (DA) neurons from pluripotent stem cells that are functional and are produced more efficiently for transplantation purposes. The 3D model for propagation and differentiation of hESCs developed under program 4 and the same has been employed successfully for efficient production of DA neurons from hESCs after co-culture with stromal cells plus growth factors for 28 days.
Investigators: Jaemin Kim and Kuldip Sidhu
3. Generating disease-specific stem cell lines
3.1 Modelling Alzheimer’s disease using human induced pluripotent stem cells
Induced pluripotent stem cells (iPSCs) are much like hESCs in their abilities to self-renew indefinitely and form any cell type. Another advantage of iPSCs is that they can be derived autologously from a patient, therefore it is anticipated that transplantation of these cells will not result in immune rejection. We have successfully generated iPSCs from human fetal fibroblasts under feeder and feeder-free conditions with the four pluripotent factors. Through collaboration with the Neuropsychiatry Institute, we also generated disease-specific iPSCs from patients with an early onset of Alzheimer’s disease. Such disease-specific cell lines present themselves as an excellent model to study the disease process in vitro and used for drug discovery.
Investigators: Henry Chung, Daniel Lie, Ruby Lin and Kuldip Sidhu
4. Tissue engineering using 3D propagation of stem cells
4.1 Encapsulation of stem cells as a 3D model for propagation and differentiation
We have previously optimized a three dimensional (3D) propagation of hESCs in calcium alginate capsules for mass production and differentiation. The same technology is now being used for other stem cell types for the propagation and differentiation of DA neurons from hESCs.
Investigators: Jaemin Kim and Kuldip Sidhu
5. New research projects
5.1 International Stem Cell Initiative (ISCI) on stem cell quality control
SCL has formally signed an agreement with the Medical Research Council (London, UK) on behalf of the International Stem Cell Forum, to participate in the quality control of stem cells produced in different laboratories worldwide for harmonizing the protocols. SCL has contributed Endeavour-2 line for such studies.
Investigator: Kuldip Sidhu