Professor at UNSW Medicine, Centre for Healthy Brain Ageing, UNSW, Sydney, Australia
Keynote: Patient-derived Induced Pluripotent Stem Cells Technology towards modelling Alzheimerâ€™s disease.
Time : 11:45-12:30
A/Professor Kuldip Sidhu had training with Prof James Thompson, Wisconsin USA (2000) who produced the first human embryonic stem cells in 1998 and Prof Shinya Yamanaka (2007-12), the Noble Laureate who developed iPSC technology and published data in Nature Biotechnology
His research focus is on neural stem cells derived from both the embryonic and non-embryonic sources for developing future cell therapies for various neurodegenerative diseases, like Alzheimer’s, Parkinson’s and other neuronal diseases. His lab was first to produce two hESC lines, Endeavour (E) 1&2 from Australia and E2 is listed on NIH registry USA for distribution and several iPSC clones from Alzheimer’s patients for disease modelling. He is an author of two book, fifteen book chapters and 170 papers including abstracts.
Dementia is the third most leading cause of death after heart disease and stroke. Huge economic impact, in 2010, 604 billion dollars spent worldwide and now 818 billion in 2015 and would be 2 trillion in 2030 because of no cure. Alzheimer’s disease is represented in majority of dementia patients and characterized by the progressive loss of specific cholinergic neurons in the brain, which leads to gradual loss of bodily functions, long term memory loss and eventually death. The pathology of AD remains elusive due to the lack of appropriate animal and/or in vitro models, which recapitulate the human AD. The induced pluripotent stem (iPS) cells derived from patient's somatic cells and thus patient specific and disease-specific iPS cells offer great potential in regenerative medicine, in drug discovery and modelling disease processes in vitro. We report here the first generation of feeder-free iPS cells from Alzheimer's patient with an early onset of disease. These cells are produced by using a polycistronic lentiviral vector containing four pluripotent genes, Oct4, Sox2, Klf4 and cMyc. These iPS cells are pluripotent as demonstrated by both the in vitro and in vivo assays. These iPS cells have been analysed by using the microarray chip and the computation of data is assisting in developing the in vitro models for this disease and for future regenerative medicine. Genome-wide microarray analysis revealed that AD-iPS cells are similar to control iPS cells and hESC lines; however, eight candidate genes differentially expressed between familial iPS cells and sporadic iPS cells. These cells exhibit disease-specific phenotype when cultured & differentiated to relevant neurons in vitro and when coaxed with specific inducers/stressors. These phenotypes could be ameliorated by using some anti-inflammatory drugs. The data indicated that it is possible to model disease in vitro and developing future therapeutics using these cells.