Could this be the key to successfully using pig organs?

A new study released earlier this week reveals the single-cell level changes that occurred before, during, and after recent xenotransplantation surgeries.^[] The researchers evaluated pig-to-human kidney transplants, transplanted in brain-dead, deceased donor bodies in September and November 2021.^[]

Overall, the findings show that the pig-organ transplants have been largely successful and have not been met with hyperacute rejection. However, they did notice some early signs of antibody-mediated rejection (AbMR)—which they say will need to be studied further in order to improve future transplants in non-brain-dead recipients. The first pig-to-human kidney transplant of that kind was successfully initiated by surgeons at Massachusetts General Hospital this March.^[]

Study authors say lack of organ rejection is a big success

None of the studied pig-to-human organ transplants showed signs of hyperacute rejection.

Jef Boeke, PhD, a co-senior author on both studies and director of the Institute for System Genetics at NYU Grossman School of Medicine, explains that had hyperacute rejection been present, it could have presented as “immediate or near immediate loss of organ function along with a blackened or mottled appearance upon revascularization.”

Because none of these signs were noticed, the overall acceptance of the transplants should be considered a “big success,” he adds.

Early signs of antibody-mediated rejection (AbMR) could be worrisome

The studies found early signs of AbMR associated with pig organ transplants. While these could be worrisome, it could also be soon to say. Boeke explains that AbMR can be a factor in any organ transplant, including human-to-human procedures. As long as this type of rejection can be managed, people can still live with the organ for years, he says.

With that in mind, Boeke says that the AbMR finding “is of course concerning but perhaps not overly so.” 

“The key question is whether the AbMR signal goes away with time, or diminishes, to the point where it can be managed with immune suppression,” he says.

“It may be mostly a response like wound healing—which could be neutral or even good,” He adds. Less likely, he says it could also be a sign of an “uncontrolled growth like in a tumor (unlikely) which would be bad.”

“Bottom line, we don’t have a definitive answer yet as to the meaning of it,” Boeke says.

Additionally, it is unclear if some of the niche cell changes seen in pig-kidney transplants are also present in human organ transplants.

“It is possible that this sort of thing happens with normal transplants also, and we just don’t have a good way to see it,” Boeke says. “When you are trying to distinguish between pig DNA and human DNA it is easy—there are many differences. Thus picking up a tiny number of cells is easy. Doing this to distinguish between two humans is much harder.”

Improving pig transplants for the future

Going forward, Boeke says “We will need to do longer-term studies and deeply characterize the antibody and cellular immune reactions.”

In terms of what future changes could potentially be made, he suggests that “genes identified as potentially troublesome could be removed or humanized in the pig.” He adds that this could be possible due to new sophisticated tools for “humanizing mammals” through whole gene replacement.

Exactly what these changes will be and the extent to which they should be implemented is yet to be determined.