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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.



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