Research Programs

Existing Programs

1. Developing a Skin-To-Neuron Autologous Adult Stem Cell Technology

Project 1.1
Isolation, propagation and characterisation of dog skin and human adult skin-derived neuroprogenitors
Skin-derived neuroprogenitors could be an important source of autologous cells for transplantation in various neurodegenerative diseases. We have perfected a two-stage protocol to generate a large number of such progenitors from dog skin that exhibit typical characteristics of neuronal population as demonstrated by gene and protein expression analyses. The same is being translated to human skin.
Investigators: Sophia Dean, Michael Valenzuela, Perminder Sachdev, Kuldip Sidhu

Project 1.2
Isolation, propagation and characterisation of human fetal skin-derived neuroprogenitors
Human fetal skin is a rich source of neuroprogenitors that could be an important source of cells for developing a proof-of-principle for transplantation in various neurodegenerative diseases. We have perfected protocol to generate a large number of such progenitors that exhibit typical characteristics of neuronal population as demonstrated by gene and protein expression analyses. Under 3D environment, these cells also transdifferentiate to other lineages like endoderm.
Investigators: Kuldip Sidhu, Sophia Dean, Michael Valenzuela, Perminder Sachdev

Project 1.3
Transplantation of skin-derived neuroprogenitors into the lateral ventricle of an aged rat brain as model for Alzheimer’s disease and proof of principle for cell therapy
The dog skin-derived neuroprogenitors are used for transplantation study in 18-month old Fischer rats as a proof-of-principle for Alzheimer’s disease by ascertaining the gain of function in cognition in a series of behavioural studies. Preliminary data suggest gain of function.
Investigators: Michael Valenzuela, Blossom Mak, Fred Westbrook, Glynis Bailey, Sophia Dean, Perminder Sachdev, Kuldip Sidhu

Project 1.4
A high throughput characterisation of neuroprogenitors and neural stem cells by an in-house developed neural chip
Based on earlier neural developmental studies, a series of protein markers were identified and used to construct a neural chip in collaboration with a biotech company, Medsaic, that gives high throughput analyses of these cells. Detailed comparative chip analyses of various neural stem cell lines in SCL are now being characterized.
Investigators: Kuldip Sidhu, Bo Yuan, Sophia Dean, Michael Valenzuela, Mark Curtis

2. Developing Stem Cells Therapy for Parkinson’s Disease

Project 2.1
Human embryonic stem cells (hESC) as source of dopaminergic neurons
Both genetic and non-genetic means are used to direct differentiate hESC to dopaminergic neurons by generating reporter cell lines and by co-culturing with stromal cells plus growth factors respectively.
Investigators: Jaemin Kim, Mark Curtis, Kuldip Sidhu

Project 2.2
Human mesenchymal stem cells as potential autologous source of dopaminergic neurons
As a proof-of-principle, human foetal bone-derived mesenchymal stem cells are being used to direct differentiate to dopaminergic neurons by using both genetic and non-genetic means.
Investigators: Kuldip Sidhu, Jaemin Kim, Daniel Lie

3. Generating Disease Specific Stem Cell Lines as Model to Study Alzheimer’s and Parkinson’s Disease

Project 3.1
To generate disease-specific stem cell lines by reprogramming somatic cells from patients by epigenetic means
To induce pluripotency in somatic cells from patients by iPS technology, we intend using non-genetic means such as epigenetics i.e. DNA methylation as suppose to genetic means used by others.
Investigators: Henry Chung, Kuldip Sidhu, Perminder Sachdev

Project 3.2
To reprogram somatic cells from patients to pluripotent stage by cell fusion and cell extracts from hESC
To induce pluripotency in somatic cells from patients, we intend using cell fusion technology being optimised in house in association with using cell extracts from hESC. The major objective is to use non-genetic means to obtain pluripotent stem cell lines from patients that could be used therapeutically.
Investigators: Jinnuo Han, Kuldip Sidhu, Perminder Sachdev

Project 3.3
To reprogram somatic cells from patients to pluripotent stage by somatic cell nuclear transfer (SCNT)
Earlier in DTU at the Prince of Wales Hospital KS produced hESC lines, Endeavour-1 and -2 from human embryos. To obtain patient and disease-specific stem cell lines we intend optimising human SCNT in collaboration with others including IVF company.
Investigators: Kuldip Sidhu, Henry Chung, John Tyler, Perminder Sachdev

4. Tissue Engineering by Using 3D Propagation of Stem Cells in a Bioreactor

Project 4.1
To encapsulate stem cells in barium alginate as 3D model for propagation and differentiation
We have optimised 3D propagation of hESC in barium alginate capsules and by using a bioreactor from a biotech company, Synthecon, for mass production of these cells. The same technology is now being used for other stem cell types for propagation and differentiation. We are also using collaboration with John Foster (BABS) to use smart surfaces for similar purposes.
Investigators: Methichit Chayosumrit, John Foster, Helder Marcal, Kuldip Sidhu

New Programs

1. To part take in an international initiative of quality control in hESC.
2. To develop hESC as model in drug toxicity and drug discovery.
3. To produce dopaminergic reporter neural stem cell lines in collaboration with a biotech company in USA.
4. To initiate training programs in stem cells.