Study the reactions of a brain-dead patient to a pig kidney for two months: the data will help to better manage future xenotransplantations.
The generosity of a patient who donated his body to science and his family has made it possible to study, for the longest time so far, the complex interactions between a transplanted pig kidney and the recipient’s organism. The results of the research, published on Naturewill allow the refinement of medical protocols to avoid rejection reactions in xenotransplantations.
Thyme: a calming addition
A team of surgeons from New York University Langone Health collaborated with immunologists from Columbia University to transplant a genetically modified pig kidney onto a 57-year-old terminally ill glioblastoma patient who had been declared brain dead and was being kept alive by an artificial ventilation system.
In addition to the organ, a part of the animal’s thymus was also transferred to the recipient, the gland that is part of the immune system in which T lymphocytes (the cells most involved in rejection mechanisms) develop.
The thymus teaches immune cells to distinguish between native elements, internal to the organism, and foreign elements. Previous animal studies suggested that transplanting a portion of one during xenotransplantations could have a calming effect on the recipient patient’s immune reactions. It happened like this: the tissue reduced the attacks of the human immune system on the pig kidney, and also prevented a dangerous loss of proteins through the urine due to the malfunctioning of the kidney – a serious complication of xenotransplantations that often occurs in living patients.
Essentially, for 61 days, the donated kidney did its job.
Rejection in real time
Through a detailed analysis of genetic activity and proteins produced in human and pig cells, scientists were able to predict immune attacks on the kidney up to five days before their damaging effects on tissue were seen.
They mainly observed three: a first wave, generic and non-specific, on the 21st day after the operation, by the innate immune system; a second by the macrophages on the 33rd day, during which these white blood cells attempted to incorporate the intruded cells; and a third attack on the 45th day, driven by the patient’s T cells. The latter episode was successfully treated by temporarily eliminating T cell activity in the recipient.
Few changes needed
The transplanted kidney had undergone few changes (such as to eliminate a sugar, alpha-gal, present on pig organs but not on human ones, which would have caused an immediate rejection reaction). Nonetheless, the organ was still functioning after two months, when the patient’s family chose to end the experiment.
This seems to suggest that minimally modified organs, which are easier and cheaper to produce, might work well for xenotransplantation, and that controlling the response of pre-existing T cells in patients might be more important than dedicating time and resources to a massive gene editing operation on the animal.
