Immunity can be deceived
Scientists have made stem cells "invisible" to the immune system for the first time
Geneticists from California have created a gene therapy that makes stem cells "invisible" to human immunity, and successfully tested it on "humanized" mice. Their findings and prospects for the use of such cells were presented in the journal Nature Biotechnology (Deuse et al., Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients).
"We always say that stem cells will revolutionize regenerative medicine, but immunity prevented the practical implementation of this idea. Our technique has solved this problem – now we can use the cells themselves and artificial tissues from them, without picking them up for the patient and producing them in mass quantities," Tobias Deuse from the University of California at San Francisco said (in a press release CRISPR Gene Editing Makes Stem Cells 'Invisible' to Immune System – VM).
Humans and many other living beings are affected by a number of serious diseases, the cause of which is not microbes or viruses, but disorders in the immune system, forcing its cells to attack healthy body tissues. These diseases include multiple sclerosis, lupus, type I diabetes and arthritis.
Scientists do not yet know why all these diseases arise. There are approximately equal reasons to believe that they may be a rare consequence of common infections, as well as the product of certain disorders in the work of genes and mutations in them.
Such health problems are almost impossible to eliminate, since any attempt to replace damaged organs or restore their work with the help of stem cells will lead to the reactivation of immunity and start the process of their destruction. Therefore, scientists today are thinking about how to "trick" the immune system or suppress it without making the body vulnerable to attacks by microbes and viruses.
Deuse and his colleagues solved this problem by creating a gene therapy based on the CRISPR/Cas9 editor, which makes reprogrammed stem cells and adult tissues based on them invisible to immunity.
It changes the activity of three key DNA sites associated with the work of the "friend-foe" system, which helps the body's defense systems identify foreign cells. The activity of two of them, B2m and Ciita, responsible for the work of innate and acquired immunity, was reduced to zero, and the third gene, Cd47, responsible for the production of the "don't eat me" signal, on the contrary, received several additional copies.
Such a procedure, as shown by experiments on human and mouse stem cells, made them and organs with their addition completely invisible to the immune system. Lymphocytes-"killers" and other "cleaners" of immunity ignored them even if scientists implanted human stem cells into the body of an ordinary mouse, or mouse tissues into the body of a "humanized" rodent.
Long–term observations of the life of these mice showed that gene therapy did not affect the ability of stem cells to participate in the "repair" of damaged organs, and organs based on them - in the normal functioning of the body. Moreover, experiments in test tubes have shown that they can form full-fledged tissues of the heart muscle and blood vessels without attracting the attention of the immune system, which usually watches their condition especially jealously.
The successful completion of these experiments, as Deuz notes, opens the way for the creation of "universal" donor tissues and organs that can be implanted into the body of any patient without growing them from his own stem cells. This will significantly reduce the cost of regenerative medicine and open the way for its practical application.
On the other hand, the authors of the article also recognize that these cells have potentially dangerous qualities – they can give rise to incurable cancerous tumors or become a breeding ground for viruses and bacteria. Therefore, they plan to insert another set of genes into them, which will allow them to be eliminated by giving a special chemical signal, if necessary.
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