Leg transplanted onto rat using trick inspired by cancer cells © UPMC

Leg transplanted onto rat using trick inspired by cancer cells

This method would mean transplant patients wouldn't have to take immunosuppressant drugs for the rest of their lives.

  • Scientists have successfully transplanted a black rat’s leg onto a white rat’s body, despite it being a complete mismatch.
  • The researchers used techniques inspired by cancer cells to trick the body into accepting foreign tissue.
  • The rat was healthy for the whole time it was monitored, almost a year in total.
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Researchers at the University of Pittsburgh have successfully transplanted a leg from a black rat onto a white rat using particles engineered to trick the body into accepting foreign tissue as its own.

Inspired by a tactic cancer cells use to evade the immune system, the cell-sized microparticles allowed the rats to develop permanent immune tolerance to transplants by releasing a protein secreted by tumours, known as CCL22, which drew T cells to the site of the graft, and tricked the immune system into thinking the foreign tissue was native.

“It’s like hacking into the immune system borrowing a strategy used by one of humanity’s worst enemies to trick the body into accepting a transplant,” said senior author Steven Little of the Swanson School of Engineering at the University of Pittsburgh.

Though developing the technique was far from straightforward, the procedure itself is much simpler to administer than existing treatments. All it took was two shots of the treatment to create a seemingly permanent change. The microparticle-treated animals maintained healthy for as long as they were monitored – a little under a year, the researchers say.

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“Instead of isolating cells from a patient, growing them up in the lab, injecting them back in and hoping they find the right location, we’re packaging it all up in an engineered system that recruits these naturally occurring cells right to the transplanted graft,” said lead author Dr James Fisher, a postdoctoral researcher in the Pitt School of Medicine.

Currently, transplant patients need to take daily doses of immunosuppressant drugs to avoid rejection, leaving them vulnerable to cancer, diabetes, infectious diseases and a host of other ailments that come along with a weakened immune system.

The risks of lifelong immunosuppression are particularly problematic when the transplant isn’t a life-saving procedure. This can make it difficult for doctors and patients have to consider whether the benefits outweigh the risks, the researchers say.

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“These drugs hammer the immune system into submission so it can’t attack the transplanted organ, but then it can’t protect the body either,” said co author Stephen Balmert, a postdoctoral researcher in the Pitt School of Medicine. “We’re trying to teach the immune system to tolerate the limb, so that a transplant recipient can remain immunocompetent.”

Xenotransplantation: could a pig’s heart save your life?

In 2016 it was announced that researchers at the National Institutes of Health (NIH) in the US had kept a genetically engineered pig’s heart beating in a baboon for three years. Though it was undoubtedly a headline-grabbing story, there are serious implications for the research.

Every year, several million people die worldwide because of transplant shortages. There just aren’t enough human organs from tragedies like road accidents to go around. But some scientists are working on a radical solution – to use organs from animals.

Xenotransplantation, as the procedure is known, may sound like something from a science fiction movie but doctors and scientists have been trying to develop it for decades.

Back in 1984, Stephanie Fae Beauclair, generally known as ‘Baby Fae’, was born with a heart defect that would have killed her within a week or so. At that time, transplants using infant human hearts were nearly always unsuccessful.

But her surgeon, Leonard Lee Bailey, was a pioneer in animal-animal transplants so decided to try transplanting a baboon heart. The hope was that it would allow Baby Fae to live long enough for a second operation to replace the baboon heart with a human one.

The surgery was initially a success, but Baby Fae died 21 days later when the heart was rejected by her body. Nevertheless, her sad story marks the first serious attempts at xenotransplantation. But 30 years on there are still many questions to be answered. Is xenotransplantation even feasible, and is it ethical?