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A serious obstacle to human stem cell treatment has been discovered

Margarita Paimakova, Vesti

The main advantage of stem cells is that they are a kind of unique repair material – they can be transformed into cells of any tissue. The body uses stem cell storage throughout its life to heal damage that accumulates with age. However, these banks of always young cells are not infinite. Therefore, scientists around the world are learning to "reprogram" the cells of an adult organism (which have already become, for example, skin) back to a young state, in order to then use universal cells to treat a particular disease.

Such cells are called induced pluripotent stem cells (iPSCs): induced, because they were actually forced to become stem cells again, and pluripotent, because they can turn into bone tissue cells, even muscle (or any other). iPSCs have already shown their suitability for clinical use (and specifically on elderly patients). However, the results of a new study conducted by specialists from the Oregon Health Sciences University (Study: Hidden genetic mutations in patient-derived stem cells could ultimately determine therapeutic benefit) showed that there is still a lot of work to be done before the widespread use of this technique can begin.

The older the patient gets, the more likely it is that adult cells obtained from his body will carry a number of genetic mutations, which, in turn, can affect the work of cells "reprogrammed" back into young ones. These mutations occur in the DNA of mitochondria – organelles that feed cells and have their own genomes. Each cell can contain hundreds of mitochondria.

In order to test exactly how genetic changes in mitochondria can affect pluripotent cells, a team led by reproductive biologist Shoukhrat Mitalipov collected skin and blood samples from a 72-year-old volunteer. Scientists sequenced the DNA of the samples, and then transformed adult cells into stem cells by using viruses (viruses cannot infect cells, but by changing their DNA, they cause the expression of several genes that work in the early stages of embryonic development).

When the researchers isolated and sequenced DNA from the resulting stem cells, they did not find a high mutation rate in the mitochondria as a whole. However, when they examined the DNA of individual cells selected randomly, they found a wide variety of mutations in the mitochondria, unnoticed by a general glance.

After that, the scientists analyzed skin and blood samples taken from 14 people aged 24 to 72 years. And the older the participant was, the more mutations in his mitochondria were detected. Several mutations affected a protein gene that can affect how well pluripotent cells will function when transplanted into a patient's body.

Mitalipov himself suggests that researchers who are going to use pluripotent cells for treatment should isolate at least a dozen cells, and then use one of them with the best mitochondria to create a cell line that will be used for therapy.

Figure from an article in Cell Stem Cell – VM

Also, according to him, these findings support the use of a technique known as therapeutic cloning, in which stem cells are created by transferring the nucleus of a sick person's cell into a healthy young cell, deprived of its own nucleus, but having healthy mitochondria. This modified cell is then used to generate a blastocyst, or human embryo, at an early stage of development, which contains the mitochondria of a healthy donor and the DNA of the patient's nucleus. However, this technology is too complex and is still available to only a few laboratories in the world.

These results also became an argument in favor of using embryonic stem cells instead of pluripotent ones.

In the future, Mitalipov's team plans to conduct a series of studies that will show how significant such mitochondrial mutations are.

A scientific article on the problem was published by Cell Stem Cell: Kang et al., Age-Related Accumulation of Somatic Mitochondrial DNA Mutations in Adult-Derived Human iPSCs.

Portal "Eternal youth" http://vechnayamolodost.ru  18.04.2016