Biologists have found problems in pretending cells
Julia Rudy, Membrane
based on the materials of the Salk Institute for Biological Studies:
Cell reprogramming leaves a "footprint" behindAbandoning the use of embryos in favor of reprogramming the cells of an adult organism may not be a very successful solution.
Molecular geneticists from the USA have shown that altered cells do not completely return to the embryonic state.
Recall that embryonic stem cells (ES cells) can be converted into cells of any type. This ability made their use as "progenitors" of artificial organs promising, as well as their use in new methods of treatment and testing of the latest pharmacological developments. However, shortly after the advent of the new technology, the destruction of embryos for the sake of obtaining these "Grail cells" was recognized as unethical almost all over the world.
Instead of ES cells, geneticists created iPS cells, which in all respects did not differ from embryonic cells. But after a while, "ineffective" groups of genes were found in the DNA of reprogrammed mouse cells.
Now, a team of researchers led by Joseph Ecker from the Salk Institute claims that in humans, reprogrammed cells behave differently from embryonic stem cells, namely that they "remember" what they were before.
Scientists analyzed the processes of DNA methylation in the genomes of 15 cell lines of different types. Among them were human embryonic stem cells, induced pluripotent stem cells and tissue cells from which they were taken, as well as differentiated (determined with their functions) cells of an adult organism derived from both types of stem cells.
It turned out that the nature of epigenetic changes (they affect gene expression, but do not change the sequence of nucleotides in DNA) in iPS cells is still different from that of ES cells. That is, there is no complete return to the embryonic state.
In an article published in the journal Nature (Ryan Lister et al., Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells), scientists write that DNA methylation at the ends and centers of human iPS cell chromosomes is similar to the processes occurring in adult tissues, the sources of these reprogrammed cells.
Embryonic cells don't have anything like that by definition. It is not yet clear whether this difference affects the ability of induced pluripotent cells to form tissues of any type. But certainly they can no longer be called a complete replacement for human ES cells.
By the way, earlier such differences in methylation processes were found in mouse stem cells (see the article "Vindictive induced pluripotent stem cells" — VM.), but they managed to get rid of them. But no tricks yet allow us to get rid of epigenetic markers in human iPS cells.
Meanwhile, Nature adds even more fuel to the fire, noting that both the cells pretending to be young and their embryonic "brothers" may not be suitable as a good model of the disease and used to treat diseases. (Flaw in induced-stem-cell model. Adult cells do not fully convert to embryonic-like state.)
That's because both types have genomic anomalies. ES cells carry duplicates of DNA pieces responsible for self-renewal in their genome, and reprogrammed cells contain more cancer—causing genes and fewer tumor suppressor genes (tumour-suppressor gene). Perhaps this is the result of the fact that the reproduction of cell lines is carried out outside the body, in unnatural conditions for them. (For a brief retelling of the review "Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramminh and time in culture", see the article "Genetic instability of human pluripotent cells" — VM.)
The general disappointing conclusion is that none of the scientists will now be able to predict how the detected differences will affect organs, tissues and the body as a whole, as well as what consequences the use and introduction of reprogrammed cells will lead to.
Portal "Eternal youth" http://vechnayamolodost.ru11.02.2011