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CRISPR technology allowed stem cells to be invisible by the immune system.

Invisible stem cells

Organ and tissue transplantation is a practice that has used long and actively in medicine. However, experts are still struggling with the problem of transplanted elements rejection, which the recipient's body perceives as alien and dangerous, with necessity to destroy them. Scientists from San Francisco have proposed a solution - the use of stem cells, artificially modified so immune system simply ... "not see" them!

Scientists argue for a long time about the potential of pluripotent stem cells. “This is the name of cells capable of differentiating into cells of absolutely any type, from which, accordingly, any tissue can develop. This was the reason for finding a mechanism for their introduction into the body in order to treat many diseases. However, a powerful force stood in the way of experiments - the human immune system, which is extremely aggressive towards everything alien”, says the author of the study, Tobias Deuse, MD.

Tobias Deuse, MD.

Tobias Deuse, MD., photo WEB

The natural defense of the human body from pathogens is programmed to destroy "outsiders" - agents from another, distinct from its own, DNA. These are viruses, bacteria, fungi and, alas, donor organs and tissues. Even the organism of the future mother in the first weeks of gestation is rejected by the developing fetus, carrying an alien, paternal genetic code. To preserve offspring, the body itself depresses immunity, which causes frequent "colds" in women early pregnancy.

This experience was also adopted by physicians, they artificially lower the immune defense of a person who has undergone transplantation. “However, such an approach is dangerous - patients become defenseless against viruses and other pathogens”, notes Professor of Surgery Sonja Schrepfer, MD, Ph.D., colleague and co-author of Deuse's work.

Professor of Surgery Sonja Schrepfer

Professor of Surgery Sonja Schrepfer, photo WEB

Experts have suggested that the solution to the problem of rejection can be found in the use of reprogrammed pluripotent stem cells taken from the patient himself. After all, such material is “own” for the defense system, albeit a little “edited”. It seemed that it was time to shout “Eureka!”, but in practice, one problem was replaced by another - for the unexplained reason, not everybody's cells can be reprogrammed ...

And at this moment a revolutionary idea was born - to create universal pluripotent stem cells that would "fit" all patients. It remained for the small - to change the DNA segments of these cells so that the immune system does not distinguish them from their own. The tool has become an innovative technology for editing genes CRISPR-Cas9. As if with an exact molecular scalpel, with its help it was possible to cut out from the cells two nucleotide sequences responsible for histocompatibility. Without them, the stem cells have become almost invisible to the immune system - neither their own nor others.


CRISPR-Cas9, photo WEB

Only killer cells remained on guard, which attack foreign agents that do not have a specific protein on their surface. Artificially incorporating its gene into the DNA structure of modified stem cells, the scientists found that they obtained a completely universal material that does not cause absolutely no immune activity in the recipient’s body.

Three-component modified mouse cells were first introduced to animals with natural immunity. Then, human stem cells, modified in the same way, were injected into mice with humanized immunity. Both experiments were successful - there was no rejection. Continuing the research, scientists have grown from the new cells heart cells, which even formed underdeveloped blood vessels and muscle tissue. And this can already be called a scientific breakthrough.

Deuse and Schrepfer are confident that the production of universal stem cells is more efficient than their production for each individual patient. Perhaps this discovery may lead regenerative medicine to a completely different level. And now, it seems, it's time to shout "Eureka!"

Victoria Romanova, Russia, Moscow