Therapy that turns lymph nodes into livers gets first human trial

For the first time, a man has received an experimental treatment that transformed one of his lymph nodes into a functioning mini-liver. We won’t know for several months whether this treatment works, but if it does, it could revolutionize the treatment of liver disease.

“This technology could eliminate liver transplant waiting lists within the next few years,” said Michael Hufford LyGenesis is a Pennsylvania-based biotechnology company.

Eric Lagasse His colleagues at LyGenesis began developing this treatment more than a decade ago. It works by taking liver cells called hepatocytes from a donated organ and injecting them into small, bean-shaped organs called lymph nodes found throughout the body. There, cells proliferate, divide, and form blood vessels. “Over time, the lymph node disappears and what’s left is a miniature organ,” Hefford said.

Researchers discovered this phenomenon almost by accident. After having little success transplanting donor liver cells into recipients’ damaged livers, they began looking for other areas of the body where the cells could survive and injecting them into different parts of mice with liver disease. While most of the rodents died, those given the abdominal injection survived. “When we opened up the animals, we found that they had 20 to 30 very small livers throughout their body, and the lymphatic system, especially the lymph nodes, is within them,” Lagasse said.

In subsequent experiments, they inserted liver cells directly into the lymph nodes of mice, pigs and dogs and found that this transformed these organs into fully functional livers. “We don’t know what happened,” Lagasse said. “(It) is pretty extraordinary stuff, a bit science fiction in a way.”

What they do know is that the transplanted cells connect with blood vessels within the lymph nodes, allowing them to grow. The cells also communicate with liver cells to perform liver functions, but it’s not clear how.

Lymph nodes are particularly suitable for cell survival. They house important immune cells that rapidly multiply and divide within the organ during infection. “The lymph node is actually a tiny bioreactor,” Lagasse said. Additionally, there are about 800 of these cells in our bodies. “So we don’t observe any adverse effects from losing one to five lymph nodes in a surgery like this,” Hefford said.

Researchers are currently testing the therapy in 12 patients with end-stage liver disease, with the first patient receiving treatment on March 25. The surgery lasted about 10 minutes and involved inserting a tube into the throat. Ultrasound imaging allows researchers to find lymph nodes and then insert a needle through the tube to inject donated liver cells.

While the participants are doing well so far, they haven’t seen any improvement in their liver function. “These liver cells have to organize themselves. They have to signal other cell types to build the organ,” Hefford said. “So you don’t really expect to see efficacy until several months after the initial implantation.”

If the treatment does work, it could significantly reduce the number of people waiting for a liver transplant.In the United States, almost 10,000 people Waiting for one. “Today, one donated organ can treat one patient,” Hufford said. “Using this method, one donated organ can treat 75 or more patients.”

However, if a mini-liver does form, it can only partially restore lost liver function. Therefore, it is unclear what the optimal dose is for end-stage liver disease. We also don’t know how long the effects will last. It might just be enough to serve as a bridge to transplant, Hufford said.