Researchers Get the Closest-Ever Look at How the Human Body Rejects Pig Kidneys

It is notoriously difficult for transplant patients around the world to secure life-saving donor organs, thanks to limited supply, long waitlists, and complex qualification criteria. While some biomedical researchers hope to mitigate this problem by reviving dead tissue and 3D printing human organs, a favored strategy, xenotransplantation, involves taking an organ from a healthy, non-human animal and placing it in a human body. 
But there’s a problem, and a big one at that: The body naturally wants to reject any tissue it knows it didn’t manufacture. This process, known as immune rejection, is what ultimately decides whether a xenotransplant works or fails. (Unfortunately, it’s almost always the latter.) 
Hoping to someday stave off immune rejection after xenotransplantation, researchers at New York University’s Langone Transplant Institute and the Paris Institute for Transplantation and Organ Regeneration took a closer look at the process. They used spatial molecular imaging to observe how the human body interacts with tissue from transplanted pig kidneys. Their findings, which reveal not only which immune cells activate but also when they’re at their most feisty, could pave the way for clinical xenotransplantation trials here in the United States this year.
Spatial molecular imaging is a fairly new technique that combines spatial biology (which maps the location of specific molecules within tissue) with molecular imaging (which helps scientists track molecular signatures). At the European Society for Organ Transplantation (ESOT) Congress on Sunday, the researchers shared that they used the technique to monitor how immune cells responded to being married with a pig kidney. Molecular imaging allowed the team to differentiate between human immune cells and pig structural cells, revealing that the former were actually “found in every part of the pig kidney’s filtering system after the transplant.”
This meant that human immune cells weren’t simply defending their own territory, so to speak; they were also playing offense. The researchers also observed early molecular signs of pig tissue rejection at the 10-day post-transplant mark. After 33 days, immune rejection peaked, offering a potential reference window during which doctors managing real xenotransplants might look out for key signs of trouble. 
The study, which has yet to be published in full, confirms the role of myeloid cells (which act as “first responders” by calling other immune cells to action) and macrophages (white blood cells that surround and kill invasive microorganisms) in immune rejection. Combined with the researchers’ rejection window, this insight could someday help scientists devise targeted treatments that mitigate the body’s short-term immune response without compromising their long-term health.
These findings come at a critical time for xenotransplantation research. In February, the US Food and Drug Administration (FDA) gave two companies the green light to begin pig kidney xenotransplantation clinical trials with kidney failure patients. 
“Understanding the specific immune interactions at a molecular level allows us to develop targeted interventions that can prevent rejection before it escalates,” said transplant nephrologist and study lead Valentin Goutaudier. “This research lays the groundwork for safer and more effective pig-to-human transplants in the near future.”
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