In early experiments, Lagasse discovered 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 failing animal. The new livers grew to 70 percent 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 functioning,” says Lagasse.
At the University of Pittsburgh, Lagasse and his colleagues also tested the approach in pigs. In a study published in 2020they discovered that pigs regained their liver function after receiving an injection of liver cells into a lymph node in the abdomen. When the scientists examined the lymph nodes containing miniature livers, they found that a network of blood vessels and bile ducts had spontaneously formed. The more severe the damage to the pigs’ original liver, the larger the second livers became, indicating that the animals’ bodies are able to recognize and transfer responsibilities to healthy liver tissue.
“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,” said Abla Creasey, vice president of therapeutic development at the California Institute for Regenerative Medicine, about the approach to the company. “These findings suggest that such an approach could provide an alternative tissue source for patients with failing organs,”
Elliot Tapper, a liver specialist at the University of Michigan, is also excited about the prospect of turning a lymph node into a new liver. “Even though it’s not where the liver was intended to be, it can still perform some liver functions,” he says.
According to him, the most likely benefit of the LyGenesis treatment is the removal of ammonia from the blood. In end-stage liver disease, ammonia can build up and travel to the brain, causing confusion, mood swings, falls, and sometimes comas. However, he does not think that the new mini-organs can perform all the tasks of a natural liver, because they contain cell types other than hepatocytes.
One of the big questions is how many cells humans need to grow a liver large enough to take over certain vital functions, such as filtering blood and producing bile. In the LyGenesis study, three additional patients will receive an injection of 50 million cells into a single lymph node – the lowest ‘dose’. If that seems safe, a second group of four will receive 150 million cells in three different lymph nodes. A third group would receive 250 million cells in five lymph nodes, meaning it could grow five mini-livers.
The effects of therapy will not be immediate. Hufford says it will likely take two to three months for the new organ to grow large enough to take over some of the functions of the original liver. And just like organ donor recipients, test subjects will have to take immunosuppressants for the rest of their lives to prevent their bodies from rejecting the donor cells.
If the approach works, it could be a life-saving alternative to liver transplantation for some patients. “If they prove it is effective and safe,” says Tapper, “there will certainly be candidates interested in this type of intervention.”