Developing a new liver in the human body from cell sacs

Scientists injected liver cells to turn one of the lymph nodes in the human body into a second liver .

For the first time, scientists have 'grown' a miniature liver, located right inside the human body. This sounds like science fiction. In fact, this idea appeared in the medical drama Grey's Anatomy that aired in 2018. Now, biotechnology company LyGenesis is trying to turn this idea into reality.

The intravenous bag contains liver cells. (Photo: LyGenesis).

'Liver farming' does not require a transplant

Specifically, on April 2, LyGenesis announced that a volunteer was injected with donor cells to turn one of their lymph nodes into a second liver. This is part of a clinical trial, testing the treatment for 12 adults with end-stage liver disease.

These patients need a liver transplant, but the supply of donor organs is insufficient. LyGenesis hopes to promote liver tissue to grow healthy enough so that patients do not need a transplant.

'We're using the lymph node as a living bioreactor,' shares Michael Hufford, co-founder and CEO of LyGenesis. He said increasing liver mass by just 10-30% could have a big impact on patients with end-stage liver disease.

If the liver transplant procedure is successful, one donated liver has enough cells to treat 75 people. (Photo: Adobe Stock).

In the US, there are up to 10,000 people on the liver transplant list. Many people will have to wait months or years to get a liver. That number does not include people who need a new liver but are not eligible for a transplant because of other health problems.

Not all donor livers are suitable for patients waiting for a transplant. Sometimes the blood types match or they have excess fat to use. But with LyGenesis' 'liver farming' process, a donated liver has enough cells to treat 75 people, said CEO Michael Hufford.

From livers that are not eligible for transplant, LyGenesis scientists isolate and purify liver cells, stored in intravenous bags. The next step is to get the cells to the right location in the body.

Eric Lagasse, chief scientific officer of LyGenesis and a professor at the University of Pittsburgh, said healthy donor cells cannot be injected directly into a diseased liver, because they would not survive. About a decade ago, he identified lymph nodes as potential sites to grow a new liver.

Shaped like small bean-shaped masses of tissue, lymph nodes are an important part of the body's immune system, helping to fight infections. They also have the ability to expand and filter blood like the liver.

Lymph nodes are found everywhere in the body with about 500-600 lymph nodes in an adult. Therefore, scientists using a few lymph nodes to feed the liver will not affect the rest of the body.

The more the liver is damaged, the larger the newly created liver becomes

LyGenesis treatment will regenerate a cluster of lymph nodes in the abdomen with a system of veins connected to the liver. With the first patient, doctors threaded a thin, flexible tube with a camera on the end, down the throat and through the digestive tract. Using ultrasound waves, they located the lymph node cluster and injected 50 million liver cells into it.

LyGenesis chose lymph nodes near the liver to take advantage of the signals it emits when filtering foreign substances in the body. The liver is the only organ that has the ability to regenerate. Even when damaged, it can still release growth factors and other molecules to carry out the regeneration process. In theory, donated liver cells will receive those signals to form new liver structures.

Lymph nodes will be injected with liver cells to form a second liver. (Photo: Lagasse Lab).

In early experiments, Lagasse discovered that if healthy liver cells were injected into the lymph nodes of mice, the cells would grow strongly and form a second, smaller liver to take on other functions. liver function is impaired. The new livers are 70% the size of the original liver.

'The second liver has grown to a certain size. It will stop growing when it reaches the level needed to perform normal functions ,' the scientist told Wired.

At the University of Pittsburgh, Lagasse and colleagues tested this method on pigs. In a study published in 2020, they found that pigs regained liver function, after being injected with liver cells into abdominal lymph nodes.

When they examined the lymph nodes with the miniature liver, they realized that a network of blood vessels and bile ducts had naturally formed. The more seriously the damage to the pig's original liver, the larger the second liver. This shows that the animal's body can recognize healthy liver tissue and transfer function to it.

But the question is how many cells humans need to develop a liver large enough to take on important functions such as filtering blood and secreting bile. In the LyGenesis trial, 3 patients will be injected with 50 million cells into a lymph node. The second group of 4 patients will be injected with 150 million cells into 3 different lymph nodes. The third group will receive 250 million cells in five lymph nodes, meaning they could have five mini livers growing inside.

The effects of therapy will not happen immediately. Hufford said 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 like organ recipients, patients participating in the trial will have to take immunosuppressant drugs for the rest of their lives to prevent their bodies from rejecting the donor cells.

If this method is effective, it will be an alternative to the traditional liver transplant procedure, thereby saving many patients' lives, Wired said.