EDEN PRAIRIE, Minn. (AP) — The ghostly shape floating in a large jar had been the robust reddish-brown color of a healthy organ just hours before. Now they are white, semi-translucent tubes, like the branches of a tree, sticking out.
This is a pig’s liver being gradually transformed to look and act like a human, part of scientists’ long-running quest to facilitate the nation’s transplantation. shortage through bioengineering of replacement organs.
The first step for workers at this suburban Minneapolis lab is to shampoo the pig cells that made the organ do its job, their color gradually fading as the cells dissolve and are removed. What remains is a rubbery scaffolding, a honeycomb structure of the liver, its blood vessels now empty.
Next, human liver cells, taken from donated organs that cannot be transplanted, will flow back into that shell. Those living cells move into the nooks and crannies of the scaffolding to restart the organ’s functions.
“Essentially, we regenerate the organ,” said Jeff Ross, CEO of Miromatrix. “Our bodies will no longer view it as a pig organ.”
That is a bold claim. Sometime in 2023, Miromatrix plans to conduct the first human trials of a bioengineered organ to begin testing it.
If the Food and Drug Administration agrees, the initial experiment will be outside the patient’s body. The researchers would place a human-turned-pig liver next to a hospital bed to temporarily filter the blood of someone whose own liver suddenly failed. And if that novel “liver assist” works, it would be a critical step toward finally attempting a bioengineered organ transplant, likely a kidney.
“It all sounds like science fiction, but it has to start somewhere,” said Dr. Sander Florman, chief of transplantation at New York’s Mount Sinai Hospital, one of several hospitals already planning to participate in the liver-support study. “This is probably more of the near future than xenotransplantation,” or the direct implantation of animal organs into people.
More than 105,000 people are on the waiting list in the United States for an organ transplant. Thousands will die before it is your turn. Thousands more are not even included in the list, as it is considered too remote a possibility.
“The number of organs that we have available will never be able to keep up with the demand,” said Dr. Amit Tevar, a transplant surgeon at the University of Pittsburgh Medical Center. “This is our frustration.”
That is why scientists look for animals as another source of organs A man from Maryland lived two months after receiving the world’s first heart transplant from a pig last January, an animal genetically modified so that its organs would not trigger an immediate attack by the human immune system. The FDA is considering whether to allow additional xenotransplantation experiments using gene-edited pig kidneys or hearts.
Organ bioengineering is markedly different: no special pigs are required, just organ scraps from slaughterhouses.
“That’s something that, in the long run, will very likely contribute to the development of organs that we can use in humans,” said Tevar of Pittsburgh. He is not involved with the Miromatrix, and he cautioned that the planned out-of-body tests would only be an initial first step.
The Miromatrix approach stems from research in the early 2000s, when regenerative medicine specialist Doris Taylor and Dr. Harald Ott, then at the University of Minnesota, pioneered a way to completely decellularize a woman’s heart. dead rat. The team seeded the resulting scaffold with immature heart cells from baby rats that eventually caused the tiny organ to beat, garnering international headlines.
Fast forward, and now in the university spin-off Miromatrix sit rows of large jugs that pump fluids and nutrients to livers and kidneys in various stages of their metamorphosis.
Removing the pig cells eliminates some of the risks of xenotransplantation, such as lurking animal viruses or hyper-rejection, Ross said. The FDA already considers decellularized pig tissue safe for another purpose, using it to make a type of surgical mesh.
More complex is getting human cells to take over.
“We can’t take billions of cells and push them into the organ all at once,” Ross said. When infused slowly, “the cells crawl out and when they see the right environment, they stick.”
The source of those human cells: donated livers and kidneys that 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 took too long to find a match.
As long as there are enough cells working when donation pools offer an organ, Miromatrix biologists isolate usable cells and multiply them in lab dishes. From a salvaged human organ, the company says it can grow enough cells to repopulate various pig liver or kidney scaffolds, cells responsible for different jobs, like lining blood vessels or filtering waste, for example.
In 2021, researchers at Miromatrix and the Mayo Clinic reported that they successfully transplanted a version of bioengineered livers into pigs.
That laid the groundwork for testing a “liver support” treatment similar to dialysis, using bioengineered livers to filter the blood of people with acute liver failure, a life-threatening emergency. Doctors now have little to offer except supportive care, unless the person is lucky enough to receive a quick transplant.
“If you can get over the hurdle, then you might recover,” because the liver is the only organ that can repair itself and grow back, Mount Sinai’s Florman said. “I will be excited when they enroll their first patient and hopefully it will be with us.”
It’s unclear how soon testing can begin. The FDA recently told Miromatrix that it has some questions about the study request.
If the liver-out-of-body experiment works, what’s next? There is still more research aimed at trying one day to transplant a bioengineered organ, probably a kidney, because a patient could survive on dialysis if the operation fails.
Although kidney regeneration is not that far along, “I was completely amazed” by the progress so far, said Dr. Ron Shapiro, an expert in kidney transplants at Mount Sinai.
He treats many older dialysis patients who “will wait years and years to get a kidney and probably die waiting on the waiting list for who would be perfect” for such experiments, if they arrive in time.
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