Donor immune cell injections reduce the risk of transplant rejection
Researchers have found a way to avoid long-term immunosuppression in organ transplants.Researchers at the University of Pittsburgh School of Medicine have injected donor immune cells into recipients before transplantation to suppress rejection during organ transplantation. Results from the first clinical trial show that this method is safe, reduces the risk of immunosuppression, and will allow for faster discontinuation of immunosuppressive drugs.
To participate in the first phase of clinical trials, scientists selected patients who required a liver transplant from a living donor. 15 participants were injected with donor immune cells into their blood one week before the transplant. The results in this group were compared with a control group of 40 patients who received liver transplants using the traditional method.
A few weeks before the operation, the scientists took blood from the donors and isolated monocytes from it. These are large white blood cells that are part of the innate immune system. The researchers stimulated the monocytes to produce regulatory dendritic cells (DCregs). These help the rest of the immune system distinguish foreign cells from its own.
DCregs were injected into the patients' blood one week before transplantation. Further surgery was performed according to the classical protocol and patients were given standard doses of immunosuppressant drugs after surgery. Clinical trials showed that immune cell infusion was safe. There were no differences in postoperative complications or acute rejection in the two groups.
The transplanted DCreg persisted in the recipients' blood for only a few days. But during that time, the cells produced exosomes that act as messengers. These tiny particles transmit "messages" from one cell to another and control their behavior. Donor exosomes prepare the body for transplants by making the body perceive transplanted cells as safe, scientists believe.
The researchers compared performance in patients who were injected with DCregs and a control group one year after transplantation. In the blood of patients in the first group, the number of other immune cells associated with inflammation and graft rejection decreased. A similar effect in animals allowed the dosages of immunosuppressants to be reduced and the therapy to be phased out.
Immunosuppressants suppress immune function and reduce the risk of developing rejection after transplantation. But long-term use of such drugs is associated with the development of a large number of side effects: including the development of cancer, diabetes, kidney failure and susceptibility to infections. The new method, if successful in further clinical trials, will reduce the duration of therapy with immunosuppressants, the scientists believe.