Liver Regeneration

The liver has the greatest regenerative capacity of any organ in the body. Liver regeneration has been recognized for many years, dating all the way back to Prometheus in ancient Greek mythology.

When the liver is injured beyond its ability to regenerate itself, a liver transplant is the treatment of choice. Transplants are used to treat a wide range of liver conditions, including liver cancer, cirrhotic liver disease, acute liver failure and genetic liver disorders.

But as is true for most donor organs, livers are in short supply — the number of people awaiting new livers far exceeds the number of donor livers available.

Focus areas

Mayo Clinic transplant surgeons, hepatologists and other researchers in the Center for Regenerative Biotherapeutics are developing and refining a number of regenerative liver therapies for patients who today must wait for whole-liver transplants.

• Extracellular vesicle-based therapies. Mayo Clinic researchers have shown that biological nanoparticles called extracellular vesicles secreted by stem cells can reduce tissue damage in the liver and could enhance repair and regeneration. Center for Regenerative Biotherapeutics researchers are now designing and developing scalable manufacturing processes for bringing stem cell-derived vesicles to the clinical setting as a novel therapeutic approach to treat liver injury.

• Living-donor transplants. Liver cancer and advanced cases of cirrhotic liver disease may require liver transplants. Given the shortage of whole livers for transplant, Mayo Clinic's campuses in Minnesota and Arizona have been performing living-donor liver transplants for more than a decade — together, they represent one of the largest such programs in the country.

  In a living-donor transplant, a portion of a donor's liver is removed and used to replace a patient's diseased liver. After surgery, the donor's liver regenerates back to full size, while the patient's new liver also grows to a normal size.

  As the safety of living donors is paramount to the success of this program, Mayo Clinic researchers have conducted a long-term assessment of donor outcomes, such as liver regeneration and mental and physical well-being. The study's results were very reassuring, as they showed that Mayo living liver donors do well after donation.

• Liver assist devices. Several types of bioartificial livers — devices that perform liver functions for patients with liver failure — have been developed in recent years. These devices support patients as their livers recover from disease or as they await liver transplants.

  Center for Regenerative Biotherapeutics researchers are refining their own version of a bioartificial liver, known as the Spheroid Reservoir Bioartificial Liver. This device contains pig liver cell (hepatocyte) spheroids, which replace a patient's liver function. Research into using human hepatocytes in the device is underway.

• Patient-specific liver cell transplantation. Existing liver cell transplantation procedures used to treat genetic liver diseases do not use patient-specific cells and require immunosuppression. Center for Regenerative Biotherapeutics researchers are developing an individualized approach to liver cell transplantation that uses the patient's own cells.

  With this approach, cells would be collected from the patient and gene therapy would be used to correct the genetic defect responsible for the patient's disease. The corrected healthy cells would then be transplanted back into the patient's liver. As the corrected hepatocytes were originally derived from the patient's own cells, no immunosuppressive drugs would be needed.

  Proof-of-concept studies in the first genetically engineered large animal model of a metabolic liver disease have already been shown to be curative. Mayo Clinic researchers are now planning to move this regenerative therapy to the clinical setting.