Wednesday, April 10, 2024

Therapy that turns lymph nodes into livers gets first human trial

Having a bunch of mini livers certainly changes out the potential outcome for a liver cancer patient.  And that was mostly bad news as mortality approaches 80 percent over five years.

suddenly we may just be able to place a couple of dozen mini livers while at least surgically removing most of the present liver.

sounds pretty close to a solution..

Therapy that turns lymph nodes into livers gets first human trial

An experimental therapy that grows miniature livers inside a person’s lymph nodes has been used in a human for the first time, but it will be months before we know if it fully replaces their liver function

By Grace Wade

2 April 2024

Solution with the hepatocytes (liver cells) in suspension


For the first time, a person has received an experimental treatment to transform one of their lymph nodes into a functioning miniature liver. We won’t know for months whether the therapy works, but if it does, it could revolutionise the treatment of liver disease.

“This is a technology that could, in just the next few years, potentially eliminate the wait list for liver transplants,” says Michael Hufford at LyGenesis, a biotechnology company in Pennsylvania.

Eric Lagasse at LyGenesis and his colleagues began developing the treatment more than a decade ago. It works by taking liver cells known as hepatocytes from a donated organ and injecting them into small, bean-shaped organs found throughout the body called lymph nodes. There, the cells proliferate, divide and develop blood vessels. “Over time, that lymph node will disappear and what you’re left with is a miniature organ,” says Hufford.

The researchers came across this phenomenon almost by accident. After having little success transplanting donor liver cells into a recipient’s damaged liver, they began searching for other areas of the body where the cells could survive, injecting them at different places in mice with liver disease. While most of the rodents died, those that had injections in their abdomen survived. “When we opened the animals, we found between 20 to 30 very small livers throughout their body where the lymphatic system is, particularly the lymph nodes,” says Lagasse.

In subsequent experiments, they inserted the liver cells directly into the lymph nodes of mice, pigs and dogs, finding this transformed the organs into fully functioning livers. “We don’t know exactly what happens,” says Lagasse. “[It] is something very extraordinary, to an extent a little bit science fiction.”

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What they do know is that the transplanted cells connect with blood vessels inside the lymph nodes, enabling them to grow. The researchers say the cells also communicate with cells in the liver to perform liver functions, but it isn’t clear how.

Lymph nodes are especially well suited for cell survival. They house important immune cells, which rapidly proliferate and divide within the organ during infection. “A lymph node is really a mini bioreactor,” says Lagasse. Plus, we have roughly 800 of them in the human body. “So, we’ve observed no adverse effects of losing one to five lymph nodes in a procedure like this,” says Hufford.

The researchers are now testing the therapy in 12 people with end-stage liver disease, the first of whom underwent treatment on 25 March. The procedure lasted about 10 minutes and involved inserting a tube down the throat. Ultrasound imaging enabled the researchers to find a lymph node and then thread a needle through the tube to inject the donated liver cells.

While the participant is doing well thus far, they haven’t seen any improvement in liver function. “These hepatocytes, they have to organise. They have to signal to other cell types to build the organ,” says Hufford. “So, you don’t really expect to see efficacy until a few months after the initial engraftment.”

If the treatment does work, it could dramatically reduce the number of people waiting for a liver transplant. In the US, almost 10,000 people are awaiting one. “One donated organ today treats one patient,” says Hufford. “Using this approach, one donated organ can treat 75 or more patients.”

However, if a mini liver does form, it will only partially restore lost liver function. So, it is unclear what the optimal dosage would be for end-stage liver disease. We also don’t know how long the effect would last. It may only be enough to act as a bridge to transplant, says Hufford.

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