The ghostly form floated in a large, sturdy reddish-brown jar of a healthy organ just hours before. It is now semi-transparent, with white tubes like branches sticking out.
Here’s a pig liver that’s been slowly being modified to look and function like a human liver, part of scientists’ long-running mission to reduce national transplants. short by bioengineering alternatives.
The first step for workers in this suburban Minneapolis lab was to remove the pig cells that help the organ do its job, its color gradually fading as the cells divide. destroyed and excreted. What remains is a rubber scaffold, a honeycomb structure of the liver, its blood vessels now empty.
The next human liver cells — taken from non-transplantable donor organs — will be put back inside that shell. Those living cells move into the nooks and crannies of the scaffold to restart organ functions.
“We basically regenerate organs,” said Jeff Ross, CEO of Miromatrix. “Our bodies won’t treat it as pig organs anymore.”
That is a bold statement. Around 2023, Miromatrix plans to test the first biotransformed organ in humans to begin trying to prove it.
If the Food and Drug Administration agrees, the initial experiment will be outside the patient’s body. Researchers will place a human-like pig liver next to a hospital bed to temporarily filter the blood of someone whose liver has suddenly failed. And if that novel “liver aid” works, it would be an important step towards eventually a biotech organ transplant – possibly a kidney.
“It all sounds like science fiction,” said Dr. Sander Florman, director of transplantation at New York’s Mount Sinai Hospital, one of several hospitals that have planned to participate in the liver-supporting study. have to start somewhere. “This is probably a nearer future than allogeneic transplants,” or direct transplantation of animal organs into humans.
More than 105,000 people are on the waiting list for an organ transplant in the US. Thousands of people will die before their turn comes. Thousands of others were never even included in the list, considered far-fetched.
“The amount of organs we have at our disposal will never meet demand,” said Dr. Amit Tevar, a transplant surgeon at the University of Pittsburgh Medical Center. “This is our disappointment.”
That’s why scientists are looking for ways animals as another source of organs. A Maryland man live two months after receiving the world’s first heart transplant from a pig last January – an animal genetically engineered so its organs don’t cause an immediate attack from the baby’s immune system People. The FDA is considering whether to allow additional foreign transplant experiments using kidneys or hearts from genetically edited pigs.
The bioengineered organs are markedly different – no special pigs are needed, just organs left over from slaughterhouses.
“It’s something that in the long run will most likely contribute to the development of organs that we can use in humans,” said Pittsburgh’s Tevar. He’s not related to Miromatrix – and warns that the planned out-of-body test will only be the first step.
The Miromatrix method has its roots in research in the early 2000s, when regenerative medicine experts Doris Taylor and Dr. Harald Ott, then at the University of Minnesota, pioneered a method of completely eliminating the fruit. heart of a dead rat. The team created scaffolds with immature heart cells from baby mice that eventually made the tiny organ beat, garnering international headlines.
Fast-forward, and now Miromatrix, a subsidiary of the university, has rows of large vessels that pump fluids and nutrients into the liver and kidneys during their various stages of transformation.
Removing the pig cells eliminates some of the risks of foreign transplants, such as lurking animal viruses or super-rejection, says Ross. The FDA has deemed de-celled pig tissue safe for another purpose, using it to create a surgical mesh.
More complicated is getting human cells to take over.
“We can’t take billions of cells and push them into the organ at once,” says Ross. When infused slowly, “the cells crawl around and when they see the right environment, they stick together.”
The source of those cells: the donor liver and kidney will not be transplanted. Nearly a quarter of the kidneys donated in the US last year were discarded because hospitals often refuse to transplant less than perfect organs or because it takes too long to find a suitable recipient.
As long as there are still enough active cells when the donor teams donate, the Miromatrix biologists will isolate usable cells and multiply them in lab dishes. From a rescued human organ, the company says it can grow enough cells to regenerate some pig liver or kidney skeletons, the cells responsible for different jobs – such as angiogenesis or waste filtration.
In 2021, researchers from Miromatrix and Mayo Clinic reported the successful transplant of a genetically modified version of liver into pigs.
That sets the stage for testing a “liver-supporting” treatment similar to dialysis, which uses genetically modified livers to filter the blood of people with acute liver failure, a life-threatening emergency. to life. Doctors currently have little ability to provide except supportive care unless the person is lucky enough to get a transplant quickly.
“If you can get over the tumor, then you can really heal,” says Mount Sinai’s Florman – because the liver is the only organ that can repair and regenerate itself. “I will be very excited when they have their first patient sign up and I hope that comes to us.”
It’s not clear how soon that trial might start. The FDA recently told Miromatrix that it has some questions about the study’s application.
If the outside liver experiment works, what’s next? There’s still plenty of research that aims to one day attempt to transplant a bioengineered organ – possibly a kidney, as patients can survive on dialysis if the surgery fails. .
Dr Ron Shapiro, a kidney transplant specialist at Mount Sinai, said: ‘Although kidney regeneration is not far off, “I am absolutely stunned” by the progress so far.
He treats many elderly patients on dialysis who “will wait years for a kidney and are likely to die waiting for the list of people who will be perfect” for him. such experiments – if they come at the right time.
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