Genetically engineered transplants avoid immune rejection

Researchers from the Chinese Academy of Sciences in Beijing have discovered a way to overcome the risks of immune rejection following cell and organ transplants, as well as potential tumour formation. Cell and organ transplants are often lifesaving, but patients experience long waiting lists because of the shortage of suitable donors. However, transplants formed from stem cells could relieve the constant organ donor shortage, resulting in more available transplants to a larger group of patients.

Immune rejection is a major issue with donation, whether it’s with solid tissues or cells from deceased or living donors, as the transplant will be rejected unless the donor material is carefully matched to the recipient’s immune system. Stem cell research is investigating the solutions to this problem.

Generating hypoimmunogenic stem cells, where stem cells and their derived tissues are genetically modified so that they are no longer recognised by the immune system, is one strategy. This allows transplants from a universal stock of stem cells to be produced without the requirement for immune matching. However, transplants from hypoimmunogenic stem cells have a possible risk of uncontrolled growth and tumour formation from residual immature cells within the transplant that would go unchecked by the immune system.

Dr Baoyang Hu and his colleagues overcame these issues by genetically engineering stem cells so that liver cells derived from them would be invisible to the immune system. Simultaneously, immature and potentially tumorigenic stem cells would still be attacked and eliminated by the immune system.

To achieve this, two immunosuppressive proteins were made by liver cells once they were mature. Immature stem cells did not make these proteins. Consequently, when transplanted into mice with a human immune system, immature stem cells were destroyed, and tumour formation was inhibited. At the same time, stem cell-derived liver cells were protected from an immune attack and could persist in the mice despite a lack of immune matching.

A similar approach could be used to protect other stem cell-derived tissues, like heart cells or pancreatic cells, from immune rejection. Further validation is needed about the safety and efficacy of those stem cell-derived transplants in preclinical and clinical studies.   

The research was published in Stem Cell Reports.