Study successfully grows liver ‘lobules’ in the lymph nodes of pigs

Posted on: 26th August 2020

A new study by researchers at the University of Pittsburgh School of Medicine has shown that large animals with ailing livers can grow a new organ in their lymph nodes from their own liver cells.

Vanessa Hebditch, Director of Policy and Communications at the British Liver Trust, says: “Last year over a 1,000 liver transplants took place across the UK, but there is a shortage of donors and every year about 10% of those waiting for a transplant either die or are taken off the list because they are no longer suitable for transplantation.

“Researchers have struggled for a long time to find ways that liver cells can be transplanted to replace lost liver function without the need for the transplantation of a whole liver. This research describes a new method of doing this – if it became successful in the future then fewer people might need transplants. However, it’s important to recognise that this is very early stage research and it is a long way from having implications for patient care at the moment.

“In this study, the scientists have successfully transplanted liver cells into the lymph nodes in pigs, and the liver cells have grown and organised themselves like small liver ‘lobules’ and shown evidence of normal liver cell activity. At the moment the lobules are very small and they are only able to replace around 2% of a normal liver – a transplant can replace 100% so this will be a key issue to overcome. However, it is an exciting and innovative area of investigation for us to watch in the future.”

Natural regenerators 

The chief functional cells of the liver are natural regenerators, and the lymph nodes serve as a nurturing place where they can multiply.

The study’s senior author Eric Lagasse, Associate Professor of Pathology at Pittsburgh says: “It's all about location, location, location. If hepatocytes get in the right spot and there is a need for liver functions, they will form an ectopic liver in the lymph node."

The cells of the liver normally replenish themselves, but need a healthy, nurturing environment to regenerate. However, in end-stage liver disease, the liver is bound up by scar tissue and too toxic for the cells to make a comeback. "The liver is in a frenzy to regenerate," said Lagasse, who also is a member of the McGowan Institute for Regenerative Medicine and the Pittsburgh Liver Research Center. "The hepatocytes try to repair their native liver, but they can't and they die."

Nearly a decade ago, Lagasse noticed that if he injected healthy liver cells into the lymph nodes of a mouse, they would flourish, forming an auxiliary liver to take over the tasks of the animals' genetically induced malfunctioning liver.

But mice are small. Lagasse and colleagues needed to show that a large animal could grow a meaningful mass of secondary liver tissue to overcome liver disease.

A recovery of liver function 

To mimic human liver disease in pigs, the researchers diverted the main blood supply from the liver, and at the same time, they removed a piece of healthy liver tissue and extracted the hepatocytes. Those liver cells were then injected into the abdominal lymph nodes of the same animal they came from.

All six pigs showed a recovery of liver function, and close examination of their lymph nodes revealed not only thriving hepatocytes, but also a network of bile ducts and vasculature that spontaneously formed among the transplanted liver cells.

The auxiliary livers grew bigger when the damaged tissue in the animals' native liver was more severe, indicating that the animals' bodies are maintaining an equilibrium of liver mass, rather than having runaway growth akin to cancer.

These findings bolster the results of another recent study, in which Lagasse and colleagues at Mayo Clinic showed that healthy liver tissue grown in the lymph nodes of pigs with a genetic liver defect spontaneously migrated to the animals' livers, where they replaced diseased cells and cured the animals' liver disease.

So, regardless of the cause of liver disease, Lagasse expects growing auxiliary livers in the lymph nodes will help.