Large animals with damaged livers may grow a new one in their lymph nodes from their body's hepatocytes, according to a recent study published online and forthcoming in the journal Liver Transplantation.
Human clinical trials are only a matter of time.
Pigs can grow extra livers in lymph nodes, says study
Hepatocytes are the main functional cells of the liver, and naturally regenerate — nurtured in the lymph nodes, where they can multiply, according to the study.
"It's all about location, location, location," said Eric Lagasse, senior author of the study and an associate professor of pathology at the University of Pittsburgh School of Medicine. "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."
Typically, liver cells replenish on their own, but they still need a healthy and nurturing environment to thrive. But in end-stage liver disease, scar tissue in the liver holds it back — creating an environment too toxic for cell regeneration.
"The liver is a frenzy to regenerate," said Lagasse, who's also 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."
Scaling up auxiliary liver treatment
Almost ten years ago, Lagasse noticed how injecting healthy liver cells into the lymph nodes of a mouse would cause them to thrive, growing into an auxiliary liver to take on the work of the animals' genetically-induced underperforming liver.
However, mice are small creatures. Lagasse and colleagues had to show their discovery could also grow a substantial mass of secondary liver tissue to beat liver disease.
To recreate the conditions of a human liver in pigs, the researchers channeled the main blood supply from the liver while simultaneously removing a sample of healthy liver tissue, from which they extracted hepatocytes. The same animal was then injected with liver cells, straight into the abdominal lymph nodes.
All six of the pigs in the experiment showed substantial recovery of liver function, with their lymph nodes playing host to not only thriving hepatocytes, but also a network of spontaneously-formed vasculature and bile ducts lining the transplanted liver cells, according to the study.
Auxiliary livers grow proportionately, human treatment possible
The animals with more severe liver damage saw the growth of even bigger auxiliary livers, which means the animals' bodies naturally work to maintain an equilibrium of liver mass, instead of runaway growth — as we commonly see in cancerous cells.
This research is significant because it lends further credibility to another recent study of Lagasse and colleagues at Mayo Clinic, which showed how healthy liver tissue grown in pig lymph nodes with a genetic liver defect migrated to the animals' livers on their own — replacing the diseased cells and curing the animals' liver disease.
Moreover, whether from alcoholism or hepatitis, Lagasse thinks growing auxiliary livers in lymph nodes could help move us closer to treating all liver diseases in ways more effective than ever before.