Stem cells hold a great promise
in terms of cell-based therapeutics and for understanding human
development. The field of induced pluripotent stem cells (iPSCs)
has unravelled a new era of stem cell research. Specifically, induced
pluripotent stem (iPS) cells, provide an alternative to embryonic
stem (ES) cells and a more realistic possibility to obtain a patient-based
and continuous source of cells. However, several recent studies,
as well as our own work, have indicated that iPS generation carries
the potential of causing DNA damage within the reprogrammed cells.
This presents major problems and concerns in terms of safety and
stability of iPS cells, as a source for therapy. As part of my
project, we are studying the effect of reprogramming on genomic
DNA stability using high-resolution methods for detecting DNA damage,
comparing the different methods of generating iPS cells and their
effect on genomic DNA, and determining reliable conditions for
generating safe iPS cells. We also plan to isolate the underlying
cause of DNA damage to establish techniques in order to circumvent
the occurrence of DNA damage. The project would provide the foundation
for understanding the genomic stability of iPS cells, define important
regions within the genome for maintaining DNA stability of these
cells, and offer new insight on the safety and future use of these
cells as a therapeutic model.
