Team Grows Auxiliary Livers in Swine Lymph Nodes

In a new study published in Liver Transplantation, researchers at the University of Pittsburgh School of Medicine describe how they generated auxiliary liver tissue in a swine model using the lymph nodes as hepatocyte engraftment sites. 

"It's all about location, location, location," said senior author Eric Lagasse. "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. "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.

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.