Patient-derived Stem Cells as New Frontiers for Disease Modelling with Focus on Neurodegenerative Diseases
Sidhu, Kuldip S.
MetadataShow full item record
Alzheimer’s disease (AD) is a neurodegenerative disorder and represents the most common form of dementia, affecting over 46.9 million people worldwide. AD is characterized by the progressive loss of specific 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. Here we report the first generation of feeder-free iPS cells from Alzheimer's patients with an early onset of disease 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 i.e. stem cell surface markers, gene expressions and teratomas formation after injecting these cells into the SCID mice. These iPS cells from patients that are predisposed to Alzheimer's disease have been analyzed 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. Some Alzheimer’s specific genes and pathways were overrepresented in these cells hence in vitro disease modelling possible.