For the first time, scientists are attempting to grow a new, miniature liver inside of a person. It sounds like science fiction; in fact, the idea was the plot of a Grey’s Anatomy episode that aired in 2018. Now, biotech company LyGenesis is trying to turn the concept into reality. Today, LyGenesis announced that an initial volunteer has received an injection of donor cells to turn one of their lymph nodes into a second liver. The procedure was carried out in Houston on March 25 as part of a clinical trial that will test the experimental treatment in 12 adults with end-stage liver disease. These patients usually require a liver transplant, but donor organs are in short supply. LyGenesis is hoping to spur the growth of enough healthy liver tissue that patients don’t need a transplant. “We’re using the lymph node as a living bioreactor,” says Michael Hufford, cofounder and CEO of Pittsburgh-based LyGenesis. He says just 10 to 30 percent in additional liver mass could have meaningful effects for patients with end-stage liver disease. About 10,000 people in the
United States are on the transplant list for a liver, and many will wait months or years to get one. That number doesn’t include those who need a new liver but don’t qualify for a transplant because of other health problems. Similarly, not all donor livers get matched to a patient awaiting a transplant. Sometimes they’re not the right blood type, or they may be too fatty for use. But they’re still viable for the LyGenesis process—and one donated liver has enough cells, Hufford says, to treat up to 75 people. From those discarded organs, LyGenesis scientists isolate and purify hepatocytes—the most abundant cells in the liver—and collect them into an IV bag. The next step is getting the cells to the right place in the body. Healthy donor cells can’t be injected directly into a diseased liver because they won’t survive, says Eric Lagasse, chief scientific officer of LyGenesis and a professor of pathology at the University of Pittsburgh. About a decade ago, he identified lymph nodes as a potential site for a new liver. These small, bean-shaped lumps of tissue help fight infection as part of the immune system. They also have the ability to expand and, like the liver, they filter blood. Because there are so many throughout the body—500 to 600 in adults—repurposing one shouldn’t affect how the rest do their
Job. The LyGenesis treatment targets a cluster of abdominal lymph nodes involved in a vein system that’s connected to the liver. To dose the first volunteer, doctors threaded a thin, flexible tube with a camera on the end down the patient’s throat and through the digestive tract. Using ultrasound, they identified one of the target lymph nodes and injected 50 million hepatocytes into it. LyGenesis chose lymph nodes close to the liver to take advantage of signals that it emits in an attempt to repair itself. The liver is the only organ with the ability to regenerate, and even when it’s damaged, it still releases growth factors and other molecules in an attempt to do so. The donor cells seem to pick up on those cues to form new liver structures. In early experiments, Lagasse found that if he injected healthy liver cells into the lymph nodes of mice, the cells would flourish and form a second, smaller liver to take over the functions of the animal’s failing one. The new livers grew up to 70 percent of the size of a native liver. “What happened is that the liver grew to a certain size and then stopped growing when it reached the level necessary for normal function,” Lagasse says. At the University of Pittsburgh, Lagasse and his colleagues also tested the approach in pigs. In a study published in 2020 , they found that pigs regained liver function after getting an injection of liver cells into an abdominal lymph node. When the scientists examined the lymph nodes with miniature livers, they found that a network of blood vessels and bile ducts had spontaneously formed. The more severe the damage in the pigs’ native liver, the bigger the second livers grew, suggesting the animals’ bodies may be able to recognize the healthy liver tissue and transfer responsibilities to it. “It is remarkable to identify lymph nodes as a reproducible and fertile bed for the regeneration of a variety of tissues and organs in two different animal species,” Abla Creasey, vice president of therapeutics development at the
California Institute for Regenerative Medicine, says of the company’s approach. “These findings suggest that such an approach could present an alternative tissue source for patients with failing organs,” Elliot Tapper, a liver specialist at the University of Michigan, is also excited by the prospect of turning a lymph node into a new liver. “Even though it's not where the liver was intended to sit, it can still do some liver functions,” he says. The most likely benefit of the LyGenesis treatment, he says, would be removing ammonia from the blood. In end-stage liver disease, ammonia can build up and travel to the brain, where it causes confusion, mood swings, falls, and sometimes comas. He doesn’t think the new mini organs could do all the jobs of a natural liver though, because they contain cell types other than hepatocytes. One of the big questions is how many cells it will require for humans to grow a liver big enough to take over certain vital functions, such as filtering blood and producing bile. In the LyGenesis trial, three additional patients will get an injection of 50 million cells into a single lymph node—the lowest “dose.” If that seems safe, a second group of four will get 150 million cells into three different lymph nodes. A third group would get 250 million cells in five lymph nodes—meaning they could have five mini livers growing inside them. The effects of the therapy won’t be immediate. Hufford says it will likely take two to three months for the new organ to grow big enough to take over some of the functions of the native liver. And like organ donor recipients, trial participants will need to go on immunosuppressant drugs for the rest of their lives to prevent their body from rejecting the donor cells. If the approach works, it could provide a life-saving alternative to liver transplantation for some patients. “If they prove it’s effective and safe,” Tapper says, “there will definitely be candidates that are interested in this kind of intervention.”