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How can the rejection of the body's own stem cells be prevented during transplants?

How can the rejection of the body's own stem cells be prevented during transplants?

Induced pluripotent stem cells (iPSC for short) could be a promising way to repair damaged cell tissue and thus compensate for the lack of human donor organs. Because like embryonic stem cells, iPSCs are able to transform themselves into any body cell. A team of researchers from the German Center for Cardiovascular Research (DZHK) at the University Medical Center Hamburg-Eppendorf has now found out why the newly grown, body's own cell tissue is still often rejected by the patient's immune system: the stem cells change genetically while they are in the laboratory grow the desired cell type. The scientists are now working intensively on methods that will no longer reject the cells grown in the laboratory.

iPSC arise from body cells such as skin cells. These are taken from the patient, reprogrammed into stem cells in the laboratory and then grown to the desired cell type. For example, scientists are developing new cardiac muscle cells from them to repair a heart damaged by a heart attack . IPSC have several advantages over embryonic stem cells. On the one hand, they are ethically harmless and the removal poses no risks for the cell donor. On the other hand, researchers previously assumed that the body accepted the newly grown cells well because they were developed from the body's own tissue.

Mutations are responsible for rejection

However, the body often rejects the new tissue anyway. Sonja Schrepfer from the DZHK, Tobias Deuse from the University of California in San Francisco (USA) and their team have now found that changes in the genetic information of the cells are responsible for this. They arise when the researchers reprogram and cultivate the body cells in the laboratory. These mutations change the cells so that the immune system considers them foreign and fights them when the cell tissue is reinstalled in the patient.

Mutations in body cells are usually common. However, the immune system usually eliminates these altered cells immediately, ensuring that they cannot accumulate. However, this control is lacking in the laboratory, so that the genetically modified cells continue to multiply. As a result, after a tissue transplant, patients would have to take lifelong medications that suppress the immune response - so-called immunosuppressants. These prevent the rejection of the tissue, but also have significant side effects. They damage the kidneys and liver and increase the risk of diabetes and tumors.

"Alternatively, you could give the cells a kind of camouflage cap," explains Schrepfer. "This gives the patient's body the impression that the cells produced in the laboratory are his own, so that they are no longer rejected after the transplant." The so-called stealth technology developed by Schrepfer and her colleagues is currently being intensified by the researchers checked. The researcher estimates that the technology can be used in patients in five to eight years. Another strategy would be to transplant only cells that are not mutated. However, according to Schrepfer, such a quality control would be very time-consuming and costly.

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