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VIDEO: Making pig livers humanlike in quest to ease organ shortage

Scientists looking to biomedically engineer human organs

The ghostly form floating in a large jar had been the robust reddish-brown of a healthy organ just hours before. Now it害羞草研究所檚 semitranslucent, white tubes like branches on a tree showing through.

This is a pig liver that害羞草研究所檚 gradually being transformed to look and act like a human one, part of scientists害羞草研究所 long quest to ease the nation害羞草研究所檚 transplant by bioengineering replacement organs.

The first step for workers in this suburban Minneapolis lab is to shampoo away the pig cells that made the organ do its work, its color gradually fading as the cells dissolve and are flushed out. What害羞草研究所檚 left is a rubbery scaffolding, a honeycomb structure of the liver, its blood vessels now empty.

Next human liver cells 害羞草研究所 taken from donated organs unable to be transplanted 害羞草研究所 will be oozed back inside that shell. Those living cells move into the scaffolding害羞草研究所檚 nooks and crannies to restart the organ害羞草研究所檚 functions.

害羞草研究所淲e essentially regrow the organ,害羞草研究所 said Jeff Ross, CEO of Miromatrix. 害羞草研究所淥ur bodies won害羞草研究所檛 see it as a pig organ anymore.害羞草研究所

That害羞草研究所檚 a bold claim. Sometime in 2023, Miromatrix plans first-of-its-kind human testing of a bioengineered organ to start trying to prove it.

If the Food and Drug Administration agrees, the initial experiment will be outside a patient害羞草研究所檚 body. Researchers would place a pig-turned-humanlike liver next to a hospital bed to temporarily filter the blood of someone whose own liver suddenly failed. And if that novel 害羞草研究所渓iver assist害羞草研究所 works, it would be a critical step toward eventually attempting a bioengineered organ transplant 害羞草研究所 probably a kidney.

害羞草研究所淚t all sounds science fiction-ey but it害羞草研究所檚 got to start somewhere,害羞草研究所 said Dr. Sander Florman, a transplant chief at New York害羞草研究所檚 Mount Sinai Hospital, one of several hospitals already planning to participate in the liver-assist study. 害羞草研究所淭his is probably more of the near future than xenotransplantation,害羞草研究所 or directly implanting animal organs into people.

More than 105,000 people are on the U.S. waiting list for an organ transplant. Thousands will die before it害羞草研究所檚 their turn. Thousands more never even get put on the list, considered too much of a long shot.

害羞草研究所淭he number of organs we have available are never going to be able to meet the demand,害羞草研究所 said Dr. Amit Tevar, a transplant surgeon at the University of Pittsburgh Medical Center. 害羞草研究所淭his is our frustration.害羞草研究所

That害羞草研究所檚 why scientists are looking to of organs. A Maryland man after receiving the world害羞草研究所檚 first heart transplant from a pig last January 害羞草研究所 an animal genetically modified so its organs didn害羞草研究所檛 trigger an immediate attack from the human immune system. The FDA is considering whether to allow additional xenotransplantation experiments using kidneys or hearts from gene-edited pigs.

Bioengineering organs is markedly different 害羞草研究所 no special pigs required, just leftover organs from slaughterhouses.

害羞草研究所淭hat is something that in the long term may very likely contribute to the development of organs we can use in humans,害羞草研究所 said Pittsburgh害羞草研究所檚 Tevar. He害羞草研究所檚 not involved with Miromatrix 害羞草研究所 and cautioned that the planned outside-the-body testing would be only an early 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 the heart of a dead rat. The team seeded the resulting scaffolding with immature heart cells from baby rats that eventually made the little organ beat, garnering international headlines.

Fast forward, and now at university spinoff Miromatrix sit rows of large jugs pumping fluids and nutrients into livers and kidneys in various stages of their metamorphosis.

Stripping away the pig cells removes some of the risks of xenotransplantation, such as lurking animal viruses or hyper-rejection, Ross said. The FDA already considers the 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.

害羞草研究所淲e can害羞草研究所檛 take billions of cells and push them into the organ at once,害羞草研究所 Ross said. When slowly infused, 害羞草研究所渢he cells crawl around and when they see the right environment, they stick.害羞草研究所

The source of those human cells: donated livers and kidneys that won害羞草研究所檛 be transplanted. Nearly a quarter of kidneys donated in the U.S. last year were discarded because hospitals often refuse to transplant less than perfect organs, or because it took too long to find a matching recipient.

As long as enough cells still are functioning when donation groups offer up an organ, Miromatrix biologists isolate usable cells and multiply them in lab dishes. From one rescued human organ the company says it can grow enough cells to repopulate several pig liver or kidney scaffolds, cells responsible for different jobs 害羞草研究所 the kind that line blood vessels or filter waste, for example.

In 2021, researchers with Miromatrix and the Mayo Clinic reported successfully transplanting a version of bioengineered livers into pigs.

That set the stage for testing a 害羞草研究所渓iver-assist害羞草研究所 treatment similar to dialysis, using bioengineered livers to filter the blood of people in acute liver failure, a life-threatening emergency. Doctors now have little to offer except supportive care unless the person is lucky enough to get a rapid transplant.

害羞草研究所淚f you can just get over the hump, then you might actually recover害羞草研究所 害羞草研究所 because the liver is the only organ that can repair itself and regrow, said Mount Sinai害羞草研究所檚 Florman. 害羞草研究所淚害羞草研究所檒l be excited when they get their first patient enrolled and I hope that it害羞草研究所檚 with us.害羞草研究所

It害羞草研究所檚 not clear how soon that testing can begin. The FDA recently told Miromatrix it has some questions about the study application.

If the outside-the-body liver experiment works, what害羞草研究所檚 next? Still more research aimed at one day attempting to transplant a bioengineered organ 害羞草研究所 likely a kidney, because a patient could survive with dialysis if the operation failed.

While regrowing kidneys isn害羞草研究所檛 as far along, 害羞草研究所淚 was completely stunned害羞草研究所 at the progress so far, said Dr. Ron Shapiro, a kidney transplant expert at Mount Sinai.

He treats many older patients on dialysis who 害羞草研究所渨ill wait for years and years to get a kidney and likely die waiting on the list who would be perfect害羞草研究所 for such experiments 害羞草研究所 if they come in time.

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute害羞草研究所檚 Science and Educational Media Group. The AP is solely responsible for all content.

Lauran Neergaard, The Associated Press

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