Human induced pluripotent stem cells (iPSCs) are adult body cells that have been treated in vitro to revert to a pluripotent state very close to embryonic stem cells. They were first produced in 2007, and the process of generating them has become progressively faster and more efficient. The resulting iPSCs now also have fewer defects and are less susceptible to becoming cancerous.
Although iPSCs are not precisely the same as embryonic stem cells, they share the property of lacking all traces of cellular aging, such as shortened telomeres and altered metabolism. In other words, they have been rejuvenated, having full-length telomeres and normal mitochondrial metabolism, gene expression profiles, and levels of oxidative stress.
Like other pluripotent cells, iPSCs can in principle differentiate into any type of body cell. Progress is being made in figuring out the exact recipe needed to actually produce cells that are equivalent to any adult cell type – some types are easier to make than others.
Given adult cells, of any particular type, derived from iPSCs, the natural question is whether such cells are also free of traces of aging that existed in the original adult cells from which the iPSCs were derived. The answer is that they are rejuvenated in comparison to the cells they were originally derived from – even if those original cells came from human centenarians, and (surprisingly) even if the original cells had entered the senescent stage in which they could no longer divide.
Of course, all this work was accomplished in vitro. There’s no obvious way to apply it to the whole body of an older person, or even to a complex organ. Perhaps such cells can eventually be used as a therapy for patients with Parkinson’s disease or to grow replacement arteries or tracheas. But that kind of development is still somewhere in the future.
[S]enescent cells, programmed into functional iPSC cells, re-acquired the characteristics of embryonic pluripotent stem cells.
In particular, they recovered their capacity for self-renewal and their former differentiation potential, and do not preserve any traces of previous aging. To check the “rejuvenated” characteristics of these cells, the researchers tested the reverse process. The rejuvenated iPSC cells were again differentiated to adult cells and compared to the original old cells, as well as to those obtained using human embryonic pluripotetent stem cells (hESC).
“Signs of aging were erased and the iPSCs obtained can produce functional cells, of any type, with an increased proliferation capacity and longevity,” explains Jean-Marc Lemaitre who directs the Inserm AVENIR team.
The key to this new development was finding an improved recipe for the transcription factors used to effect reprogramming. In addition to the usual four factors (OCT4, SOX2, c-MYC and KLF4), the researchers included NANOG and LIN28 to erase traces of cell senescence.