Organ transplants save lives, but unfortunately rejection is a key hurdle. Now scientists have demonstrated a potential new way to prime a recipient’s immune system to accept a transplanted organ, by first giving them an infusion of immune cells from the donor.
The human immune system is a powerful defense mechanism, patrolling the body for pathogens or foreign cells that could cause harm. But in the case of organ transplants, this overzealousness can become a disadvantage, as the immune system recognizes the new organ isn’t from around here and launches an attack. To prevent organ rejection, patients are usually given immunosuppressant drugs, but that leaves them vulnerable to other illnesses.
In a new Phase 1 trial, scientists at the University of Pittsburgh School of Medicine tested a new way to reduce the chance of organ rejection in transplant patients. They conducted the trial in 15 patients due to receive a transplant of a portion of liver from a living donor, and compared the results to 40 control patients undergoing the same procedure.
A few weeks before the trial patients underwent surgery, the scientists took blood from the donors and isolated a type of white blood cell called monocytes. These were then used to grow regulatory dendritic cells (DCregs), which play a key role in helping the immune system distinguish between friend and foe. These DCregs, newly grown from each donor, were then infused into the respective recipients one week before the transplant.
Because of the early stage of the trial, the patients were still given immunosuppressant drugs. The goal at this stage was to test the feasibility and safety of the procedure, and on those counts the treatment was a success.
The researchers did check for differences in immunologic activity that could suggest whether the treated patients might be less dependent on immunosuppressants. They found that even a year after transplantation, patients who received DCregs had lower levels of immune cells that are normally associated with rejection, compared to the control group.
“These trial results are very encouraging,” said Angus Thomson, senior author of the study. “Right now, we’re seeing preliminary evidence that this intervention is modifying the recipient’s immune response in such a way that we may be able to safely reduce — or even withdraw — immunosuppression. It would be a significant service to the transplantation community if patients are no longer dependent indefinitely on immunosuppressants.”
On closer inspection, the researchers uncovered a mechanism for how the treatment seems to work. The DCregs themselves break down after just a few days, but during their short stint they produce particles called exosomes, which help cells communicate with each other.
“We believe that these donor-derived exosomes are preemptively conditioning the prospective recipient to see donor cells as safe,” said Thomson. “A year post-transplant, clinicians will then determine which patients can start tapering off immunosuppressants. Then time will tell if our approach works.”
Other scientists have found some success recently in preventing rejection in transplant patients by growing new organs from the patient's own cells, or by using genetically engineered pig organs. The new technique could be a relatively simple method for times when the donor is still alive, such as transplants of kidneys or liver portions.
The research was published in the journal Science Translational Medicine.
Source: University of Pittsburgh
