As UC San Diego-led study shows, one of the major problems of cell transplantation – stem cell rejection – might have been solved. The study was given light in the journal Cell Stem Cell.
Researchers have found way to make transplanted cells invisible to the immune system by engineering them genetically to produce two immune-suppressing molecules. The scientists tested the method in mice and it proved successful, while the functioning of the immune system in the rest of the animal remained unaffected.
The finding still has to be tested for safety and effectiveness before it can be considered for human trials, and it will take a few more years. If the approach is effective in people, transplantation of organs and tissues produced from embryonic stem cells will not need to be accompanied with harsh immune suppression to avoid graft vs host disease.
Researchers modified stem cells by placing in them genes responsible for production of two molecules - CTLA4-lg and PD-L1 – that are made in the body in a natural way. Then they transplanted heart and skin cells produced from the engineered cells to the the mice. The cells were accepted, while unmodified – rejected.
However, some other scientists that were given the article are worried that the use of modified stem cells will cause immunosuppression leading to a loss of tumor surveillance and higher susceptibility to infections. The authors say in the paper that these dangers could be addressed by inserting a gene in the transplanted cells that will lead to cells suicide when antiviral drug gangciclovir is applied. In animal models, tumors with this gene have been eliminated with this approach.
Also, the “knock-in” technique used to genetically modify the stem cells is safer comapred with others that randomly place genes into the DNA. The latter poses a risk of tumors.
The researchers say they are also considering alternatives to genetic engineering, for example, but before any human trial, though safety tests will be carried on animals.