The Senescence-Related Mitochondrial/Oxidative Stress Pathway is Repressed in Human Induced Pluripotent Stem Cells
Prigione et al. Stem Cells. 2010 Mar 3.
Embryonic stem cells possess the ability to propagate in
tissue culture indefinitely. This is different than differentiated cells, for
example, skin cells which can only multiple in tissue culture approximately 50
times before undergoing senescence. The ability of embryonic stem cells to
escape senescence is related to expression of the protein telomerase. Usually
when cells multiply the ends of the chromosomes, called telomeres, progressively
reduce in size. When the telomeres become critically short, the gene p53 is
activated, which is involved in instructing the cells to stop multiplying and
exist in a semi-alive state called senescence. Tumor cells and embryonic stem
cells escape senescence by expressing the enzyme telomerase. This enzyme
essentially allows cells to repair their telomeres by progressively adding new
nucleic acids. Although much is known about senescence or lack thereof in adult
cells and embryonic stem cells, little research has been performed in whether
inducible pluripotent stem cells (iPS) can also escape proliferative
senescence. In a recent publication this question was examined.
In a similar manner to embryonic stem cells, iPS cells were
shown to express high levels of the enzyme telomerase, and propagation in tissue
culture was achieved up to 200 passages without senescence occurring.
Furthermore the investigators studied the mitochondrial stress pathway. It was
found that somatic mitochondria within human iPSCs revert to an immature
ESC-like state with respect to organelle morphology and distribution, expression
of nuclear factors involved in mitochondrial biogenesis, content of
mitochondrial DNA, intracellular ATP level, oxidative damage, and lactate
generation. When iPS cells were differentiated into adult cells, mitochondria
within iPSCs demonstrated maturation and anaerobic-to-aerobic metabolic
modifications. This same finding was observed in embryonic stem cells.
These data suggest that iPS cells possess several important
properties similar to embryonic stem cells, which further supports the
possibility of interchangeably using ES and iPS cells for experimental purposes.
The next question is whether iPS cells may be generated in large quantities so
that their mitochondria may be transferred to aged cells.
Another interesting finding in the current study is that
the metabolic pathway used by both iPS and embryonic stem cells is analogous to
that found in cancer cells. Therefore it will be interesting to follow studies
using iPS as a model of cancer.