Transplant surgeons, hepatologists and other researchers are developing liver cell-based regenerative therapies for patients who'd otherwise need whole-liver transplants.
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.
Mayo Clinic transplant surgeons, hepatologists and other researchers in the Center for Regenerative Medicine are developing and refining a number of regenerative liver therapies for patients who today must wait for whole-liver transplants.
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 Medicine 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 Medicine researchers are developing an individualized approach to liver cell transplantation that uses the patient's own cells.
With this approach, cells from the patient would be collected, converted to induced pluripotent stem cells in the laboratory and subsequently transformed into hepatocyte-like cells. During this process, gene therapy would be used to correct the genetic defect responsible for the patient's disease.
The hepatocyte-like cells would then be transplanted into the liver of a bioengineered pig, where they'd grow into fully functioning, patient-specific human adult hepatocytes that could be transplanted into the patient to regenerate the liver. As the new hepatocytes were originally derived from the patient's own cells, no immunosuppressive drugs would be needed.